bluuebunny/crossref_metadata_2025 huggingface dataset:
Biological Parameters for the Choice of Antiangiogenic Therapy and Efficacy Monitoring
Authors: Ziche M. , Sorriso C. , Parenti A. , Brogelli L. , Tricarico C. , Villari D. , Pazzagli M.
Published: March 2018

Angiogenesis is a tightly controlled process which depends on the balance between stimulating and inhibiting factors. When this balance is disrupted, angiogenesis acquires a pathological meaning. The list of molecules able to induce angiogenesis is heterogeneous with respect to their chemical characteristics and biological properties. Quantitative measurement of tumor angiogenesis is necessary for the choice of therapeutic strategies and as an endpoint for antiangiogenic therapy. We are developing a quantitative RT-PCR which measures the expression of specific factors in real time. With the use of this rapid technique, measurement of the expression of the angiogenic factors and inhibitors is also possible in specimens as small as biopsies.
Assessment of Tumor Vascularization: Immunohistochemical and Non-Invasive Methods
Authors: Fanelli M. , Locopo N. , Gattuso D. , Gasparini G.
Published: March 2018

Growth of solid tumors beyond a certain mass is dependent on the vascular bed from pre-existing host vasculature. The process of angiogenesis is essential not only for primary tumor growth but also for metastasis. The number of microvessels within the invasive component of a primary tumor reflects the degree of tumor angiogenesis. At present the most widely used method to assess neovascularization is the quantitation of intratumoral microvessel density (IMD) by immunohistochemical methods in which specific markers for endothelial cells are employed. In this paper we analyze the different methods used to assess IMD, as well as their advantages and potential methodological pitfalls. Several studies have shown a close correlation between IMD, tumor growth and the occurrence of metastasis, suggesting that IMD is a prognostic indicator of clinical relevance. Furthermore, preliminary studies suggest that determination of angiogenesis may predict responsiveness to some forms of conventional anticancer therapy. Although the histological microvessel density technique is the current gold standard to characterize tumor angiogenesis, it may not be the ideal tool for clinical purposes because it needs to be performed on biopsy material and does not assess the functional pathways involved in the angiogenic activity of tumors. Non-invasive assessment of tumor vascularity is possible in vivo by means of Doppler sonography, dynamic contrast-enhanced magnetic resonance imaging (MRI) and positron emission tomography (PET). These methods may be preferable to histological assay because they are non-invasive, survey the entire tumor, reflect both anatomic and physiologic characteristics, and may be useful to monitor the activity of antiangiogenic therapies.
MMP Inhibitors: Experimental and Clinical Studies
Authors: Belotti D. , Paganoni P. , Giavazzi R.
Published: March 2018

Matrix metalloproteases (MMPs) are a family of structurally related enzymes that are capable of degrading proteins of the extracellular matrix. These enzymes play a role in tissue remodelling associated with both physiological and pathogenic processes. A high expression of MMPs is associated with cancer malignancy: it is related to the tumor's ability to metastasize and to the process of angiogenesis. Treatment with MMP inhibitors alone or in combination with cytotoxic therapy is an interesting novel approach to control tumor progression. The expected mechanism of action of these compounds and the difference in side effects compared to cytotoxic drugs make the definition of endpoints and the assessment of response difficult. Furthermore, it is not yet clear whether tumor vascularization or, more specifically, MMP expression/activation should be a criterion of eligibility for this kind of treatment. This review provides an overview of the characteristics of MMPs and their role in tumor progression, metastasis and angiogenesis. Preclinical and clinical studies with synthetic MMP inhibitors are described. The presence of MMPs in biological fluids of patients and their use in prognostic evaluation and in determining the efficacy of treatment with MMP inhibitors is discussed.
Angiosuppression and Chemotherapy: Strategies Aimed at Their Integration in Cancer Patients
Authors: Cascinu S. , Valenti A. , Mesiti M. , Gasparini G.
Published: March 2018

A number of antiangiogenic agents have been developed as pharmaceuticals and are currently being tested in clinical studies. Potential strategies to enhance the activity of angiogenesis inhibitors could be to combine them, or better still, to administer them either sequentially or concurrently with cytotoxic drugs. Chemotherapy would be a more appropriate initial choice for patients with advanced disease since cytostatic agents can induce a fast regression of the tumor and cancer-related symptoms. Antiangiogenic treatment could be used after chemotherapy in patients who achieve disease remission to prolong the time to progression, the symptom-free interval and the overall survival. Antiangiogenic treatment is likely to attain an important role in the adjuvant setting. In fact, it could be used for prolonged periods after radical surgery to maintain dormancy of residual tumor cells. In spite of these promising preclinical data, several points need to be clarified before the initiation of clinical trials. In fact, certain misconceptions may interfere with their optimum design and result analysis.
Quantitative RT-PCR Assay for VEGF Mrna in Human Tumors of the Kidney
Authors: Tricarico C. , Salvadori B. , Villari D. , Nicita G. , Della Melina A. , Pinzani P. , Ziche M. , Pazzagli M.
Published: March 2018

Angiogenesis is the formation of new capillaries from pre-existing vessels, and recent evidence has demonstrated that tumor growth is controlled mainly by angiogenesis. Vascular endothelial growth factor (VEGF) is an endothelium-specific growth factor which is strongly angiogenic in vitro and in vivo. We have developed a quantitative RT-PCR assay for the measurement of VEGF mRNA expression using a real-time procedure based on the use of fluorogenic probes and the ABI PRISM 7700 Sequence Detector System. The assay performance of this method in terms of practicability and reliability is reported with results that seem promising for its widespread use in the clinical laboratory. The method has been applied to the measurement of mRNA of VEGF in human renal cell carcinomas (RCC). Preliminary results show a significantly higher VEGF mRNA expression (ratio values between 181 and 2222) in tumor specimens compared to non-adjacent, non-tumoral tissue of the same subjects.
Inhibition of Angiogenesis by Type I Interferons in Models of Kaposi'S Sarcoma
Authors: Marchisone C. , Benelli R. , Albini A. , Santi L. , Noonan D. M.
Published: March 2018

Kaposi's Sarcoma (KS) is a pathology which occurs with increased frequency and in a particularly aggressive form in AIDS patients. The HIV-1 Tat protein appears to be an important co-factor in the induction of the extensive neo-vascularization associated with AIDS-KS. Tat acts as a chemoattractant for endothelial cells in vitro, inducing both chemotactic and invasive responses. Several clinical trials have been performed testing the effectiveness of diverse biological agents in therapy of KS, among these the type I interferons. Type I IFNs have diverse biological functions besides their anti-viral activity, including anti-angiogenic properties. We have shown that IFNα and IFNβ are potent inhibitors of both primary and immortalized endothelial cell migration and morphogenesis in vitro as well as neo-angiogenesis induced by HIV-1 Tat in vivo. The inhibitory effect of IFN class I on HIV-Tat associated angiogenesis further supports its use as a therapy for epidemic Kaposi's sarcoma. The use of recombinant IFNs at the levels required to obtain a therapeutic effect are associated with side effects and toxicity, therefore we are now developing a gene therapy approach for constant and local delivery type I IFNs.
Endostatin: A Promising Drug for Antiangiogenic Therapy
Authors: Cirri L. , Donnini S. , Morbidelli L. , Chiarugi P. , Ziche M. , Ledda F.
Published: March 2018

Angiogenesis, the formation of new blood vessels from existing capillaries, is critical for tumors to grow beyond a few in size. Tumor cells produce one or more angiogenic factors including fibroblast growth factor and vascular endothelial growth factor. Surprisingly, antiangiogenic factors or angiogenesis inhibitors have been isolated from tumors. Some angiogenesis inhibitors, such as angiostatin, are associated with tumors while others, such as platelet-factor 4 and interferon-alpha are not. Endostatin, a C-terminal product of collagen XVIII, is a specific inhibitor of endothelial cell proliferation, migration and angiogenesis. The mechanism by which endostatin inhibits endothelial cell proliferation and migration is unknown. Endostatin was originally expressed in a prokaryotic system and, late, in a yeast system, thanks to which it is possible to obtain a sufficient quantity of the protein in a soluble and refolded form to be used in preclincial and clinical trials.
Student Report - The Fight against Cancer and Angiogenesis Inhibitors: Are we Entering a New Era?
Authors: Spada M.
Published: March 2018

Chemoresistance is currently the main cause of failure in the treatment of cancer which, despite extensive research, remains unsolved. In this report the theoretical assumptions underlying antiangiogenic therapy are described and future perspectives and limits are discussed.
Gender and Cartoons from Theaters to Television: Feminist Critique on the Early Years of Cartoons
Authors: Perea Katia
Published: March 2018

From adults to children, from theaters to television, cartoons are one of the few major popular art forms that have been able to consistently redefine their audience as they experiment and change and, as such, have proved their importance in culture and society. This article discusses the social critique that originated with cartoons’ theatrical beginnings, which were met with substantial praise from the intellectual and art community of their time. An exploration into the massification of the medium reveals its role in the marginalization of women in the animation industry as underpaid and unrecognized labor. This article also explores the industry’s creation of a compulsory gender coding associated with the animated female form by investigating Disney’s and Warner Bros.’ competing portrayals of women as a ‘madonna–whore’ duality, and further looks into Disney’s feminine triptych perpetuating heteronormative gender coding in the form of the princess, the witch and the fairy godmother. The massification of the medium, as television programming shaped the industry into children’s programming, was led by Hanna-Barbera who did not consider girl cartoons a priority and continued to marginalize women in the workforce.
Differential immunological profiles herald magnetic resonance imaging-defined perioperative cerebral infarction
Authors: Fanning Jonathon P. , See Hoe Louise E. , Passmore Margaret R. , Barnett Adrian G. , Rolfe Barbara E. , Millar Jonathan E. , Wesley Allan J. , Suen Jacky , Fraser John F.
Published: March 2018

Background:

The perioperative period is associated with a high risk for human ischaemic stroke. Although inflammatory mechanisms are known to have an important role in cerebral infarction in the nonoperative setting, their role in modulating perioperative risk remains unclear.

Methods:

In this prospective case-control study, we compared 10 patients (cases) who developed magnetic resonance imaging (MRI) evidence of cerebral infarction following transcatheter aortic valve implantation with 10 patients (controls) who underwent the same procedure without neurological complication. Blood sampling was performed preoperatively (baseline) and at 24 h, 48 h and 72 h postoperatively and analysed for specific cytokines, chemokines and complement factors.

Results:

Baseline serum assessments identified significant differences between the two cohorts for levels of complement C3, complement C4b, granulocyte-macrophage colony-stimulating factor, interleukin-15 and macrophage inflammatory protein-1β. Longitudinal regression analysis and best-fit polynomial curves of postoperative analyte profiles identified significantly higher levels of complement C3 and matrix metalloproteinase-9, and lower levels of interferon-γ and macrophage inflammatory protein-1β levels in cases versus controls.

Conclusions:

These results support a potentially important role for inflammatory mechanisms in MRI-defined perioperative stroke and reveal a potentially important role for complement components in this process.
Living to 100 years and beyond: Drivers and implications
Authors: Leeson George W.
Published: March 2018

The world is ageing, both at an individual and a population level, and population ageing is truly a global phenomenon. The emergence of large numbers of centenarians has accompanied this development and the twenty-first century promises to be the century of centenarians. The number of centenarians in Europe increased from around 57,000 in 2006 to almost 90,000 in 2011. By 2100 the number is expected to reach around 1.4 million in England and Wales alone. This century of centenarians will be challenging in both the developed and the emerging economies. The trend has fundamental consequences for the way in which individuals view and live these ever-extending lives, but also for the way in which societal infrastructures (education, workplaces, housing, transport, and health and social care) will need to be adapted to the needs of extreme-aged populations. More importantly, perhaps, our perception of old age needs a dramatic reappraisal.
Developing robots: The need for an ethical framework
Authors: Leveringhaus Alex
Published: March 2018

This article discusses the need for an ethical framework for emerging robotic technologies. The temptation, arguably driven by sci-fi treatments of artificial intelligence, is to ask whether future robots should be considered quasi-humans. This article argues that such sci-fi scenarios have little relevance for current technological developments in robotics, nor for ethical approaches to the subject: for the foreseeable future robots will merely be useful tools. In response to emerging robotic technologies, this article proposes an ethical framework that makes a commitment to human rights, human dignity and responsibility a central priority for those developing robots. At a policy level, this entails (1) assessing whether the use of particular robots would result in human rights violations and (2) creating adequate institutions through which human individuals can be held responsible for what robots do.
Clear skies or troubled waters: The future of European ocean governance
Authors: Germond Basil
Published: March 2018

Ocean governance is a complex process that involves many stakeholders within, across and beyond states. It currently stands high on the political and public policy agendas of European states and the EU due to the importance of the sea from both an economic and security perspective. This article aims to present the current state of European ocean governance, discussing the current trends and proposing some recommendations as to how best to tackle the challenges. It suggests that the future of European ocean governance rests on the actors’ ability to endorse a holistic approach that combines all aspects of sustainable development and security.
Co-responsibility between countries of origin, transit and destination: Lessons from Spain’s experience with migration
Authors: Senge Katharina
Published: March 2018

This article gives an overview of Spain’s experience of regular and irregular migration in the past and of the subsequent development of the EU’s framework for external migration policies. It argues for a realistic rather than ideological approach that involves co-responsibility between countries of origin, transit and destination, in compliance with human rights standards. Co-responsibility means a system in which migrants’ countries of origin, transit and destination share the burden of dealing with both regular and irregular migration whenever possible. Such a system is sometimes characterised by long and difficult discussions and negotiations to define common goals and balance interests in the spirit of a partnership of equals. This article first tackles immigration in Spain, with an emphasis on the 2006 Spanish refugee crisis or the ‘Cayucos crisis’. It then looks at EU migration policy, before recommending ways of improving it.
Calcaneal Osteotomy Safe Zone to Prevent Neurological Damage: Fact or Fiction?
Authors: Wills Bradley , Lee Sung Ro , Hudson Parke William , SahraNavard Bahman , de Cesar Netto Cesar , Naranje Sameer , Shah Ashish
Published: March 2018

Background. Calcaneal osteotomy is a commonly used surgical option for the correction of hindfoot malalignment. A previous cadaveric study described a neurological “safe zone” for calcaneal osteotomy. We performed a retrospective chart review to evaluate the presence of neurological injuries following calcaneal osteotomies and the location of the osteotomy in relation to the reported safe zone. Methods. In this retrospective study, we reviewed charts of patients who underwent calcaneal osteotomy at our institution from 2011 to 2015. All immediate postoperative radiographs were examined and the shortest distance between the calcaneal osteotomy line and a reference line connecting the posterior superior apex of the calcaneal tuberosity to the origin of the plantar fascia was measured. If the osteotomy line was positioned within an area 11.2 mm anterior to the reference line, it was considered to be inside the neurological safe zone. We correlated the positioning of the osteotomy with the presence of postoperative neurological complications. Results. We identified 179 calcaneal osteotomy cases. Of the 174 (97.2%) nerve injury-free cases, 62.6% (109/174) were performed inside the defined “safe zone” while 37.4% (65/174) outside. A total of 5 (2.8%) nerve complications were identified: 3 (60%) were inside the safe zone and 2 (40%) outside the safe zone. Osteotomies outside the safe zone had a 1.114 relative risk of nerve injury with a 95% CI of 0.191 to 6.500 and showed no statistically significant difference ( P = .9042). Conclusion. Our findings suggest that the clinical “safe zone” in calcaneal osteotomies may not actually exist, likely because of wide anatomical variation of the implicated nerves, as described in prior studies. Patients should be properly counseled preoperatively on the low, but seemingly fixed, risk of nerve injury before undergoing calcaneal osteotomy.

Levels of Evidence: Level III: Retrospective comparative study
The Ability of Fluorescence Angiography to Detect Local Ischemia in Patients With Heel Ulceration
Authors: Marmolejo Valerie S. , Arnold Jonathan F.
Published: March 2018

Heel ulcerations are a significant burden of care in both hospital and long-term care settings. The presence of peripheral arterial disease as a contributing factor to delayed healing is often not recognized, resulting in prolonged healing and high patient morbidity and mortality. Formal vascular evaluation and intervention is often not performed as these patients can have palpable pedal pulses while having localized ischemia of the heel. As routine noninvasive vascular studies can be affected by medial calcinosis and collateralization and do not specifically assess tissue perfusion to the heel, a false sense of security of adequate perfusion for healing can result. Indocyanine green fluorescence angiography (ICGFA) allows for real-time visualization and objective assessment of site specific tissue perfusion not limited by the factors that can make routine noninvasive vascular studies unreliable or unobtainable. A retrospective medical record review of a subset of patients with chronic heel ulceration from a prospective institutional review board–approved study in which serial ICGFA was performed during their treatment course was performed. ICGFA was able to identify local heel ischemia and expedite vascular intervention. ICGFA should be considered as an additional vascular study in patients presenting with chronic, nonhealing heel ulcerations.

Levels of Evidence: Level IV: Diagnostic, Case series
Hydatid disease: MR imaging of calvarium and superior sagittal sinus involvement
Authors: Demir Mustafa Kemal , Yapıcıer Ozlem , Hasanov Teyyub , Yılmaz Baran , Kılıç Türker
Published: March 2018

Extra-axial hydatid disease (HD) is rare and may create a diagnostic challenge. Herein, we report an extremely rare case of calvarial HD with superior sagittal sinus invasion and an extension to the scalp with unusual magnetic resonance imaging findings simulating osteomyelitis and abscess. Recognition of detached endocystic membranes was the most important clue for the correct diagnosis. HD should be included in the differential diagnosis for a patient having a destructive skull lesion with peripheral enhancing extra-axial soft tissue component. Preoperative correct imaging diagnosis is crucial to improving patient management.
Severe ingrown toenail with hypertrophic skin bridging: A case report and review of the literature
Authors: Preston Nathaniel LP , Halaharvi Chandana , Logan Daniel B
Published: March 2018

We present a case report of an 18-year-old male who was diagnosed with a chronic non-congenital ingrown toenail to his right hallux with skin bridging spanning the mid-portion of the nail plate. The patient elected to pursue surgical correction and underwent a Winograd procedure under monitored anesthesia care. The incision sites healed without incident.
Urinary tract infection management – do the guidelines agree?
Authors: Moon A , Veeratterapillay R , Garthwaite M , Harding C
Published: March 2018

Urinary tract infection (UTI) is defined as the inflammatory response of the urothelium to bacterial invasion. UTI in adults is one of the most prevalent infectious diseases worldwide with a substantial financial burden on society. There is mounting concern surrounding the ongoing development of microbial resistance. In addition, the increasing resistance of organisms to broad-spectrum antibiotics is worrying. There is a continuing drive for antibiotic stewardship and more prudent prescribing of antimicrobial agents. There is currently no national UK guideline on the management of UTI in adults but the EAU, AUA and SIGN all have their separate recommendations. In this review, we discuss the existing guideline recommendations particularly relating to lower UTIs (cystitis and epididymo-orchitis), upper UTIs (pyelonephritis) and catheter-associated infections (due to their large healthcare burden). The aims are to identify common recommendations and assess how they may apply for the UK setting. This review has highlighted considerable differences in practice recommendations between the major UK, European and American guidelines. Discrepancy exists in the choice of antibiotics and for some types of infection, whether or not any guidance for treatment is offered. Antibiotic avoidance and prudent antibiotic prescribing will be key components of future strategies in reducing antimicrobial resistance.
Urothelial carcinomas of the upper urinary tract – how does UK practice compare with European guidelines: is there a difference?
Authors: Moon A , Frew J , Johnson MI
Published: March 2018

Upper urinary tract urothelial carcinomas (UUT-UCs) are relatively rare tumours that present a challenge to urologists, both in terms of diagnosis and treatment. The diagnostic pathway is often complex and the surgical options continue to generate controversy. The outcomes of treatment are mixed, with invasive tumours having a particularly poor prognosis. In this article we compare UK practice with the most recent European Association of Urology (EAU) guidelines for the management of UUT-UCs.
A comparison of the National Institute for Health and Care Excellence (NICE) and European Association of Urology (EAU) guidelines for the assessment and management of urinary incontinence in women
Authors: Warner Ross M , Greenwell Tamsin J
Published: March 2018

Objective:

The objective of this paper is to identify the similarities and key differences between the National Institute for Health and Care Excellence (NICE) and European Association of Urology (EAU) guidelines on the management of urinary incontinence (UI) in women.

Methods:

We reviewed the most recent iterations of both full guidelines to identify all key recommendations and their associated level/grade of evidence. Guidance on the management of urinary incontinence in men and neuropathic patients was excluded.

Results:

There is a significant overlap in the recommendations of both guidelines. Key differences include the indications for performing urodynamics, pharmacological agents in stress UI, the dose of botulinum toxin A (200 units by NICE, 100 units by EAU), the hierarchy of surgical options for primary stress UI and the role of the multi-disciplinary team (MDT).

Conclusion:

This review provides the various stakeholders involved in the management of female UI with a summary of the strength of evidence supporting the recommendations by these two key guidelines. We have provided an evidence-based framework to support clinical experience from which to base management decisions.
Assessing Health Outcomes and Youth-Related Items for the Adverse Childhood Experiences Questionnaire
Authors: Davidson Ryan D. , Rojo-Wissar Darlynn M. , Sullivan Alyssa W. , Beck Connie J.
Published: March 2018

Recently, several researchers have suggested additional items be included to the Adverse Childhood Experiences (ACE) questionnaire for a younger population (children ages 10–17). Two sets of items have been proposed by Finkelhor and colleagues. However, it is unclear which set of items is the most useful in an emerging adult population. The current study compared the original ACE questionnaire with two revised sets of items proposed by Finkelhor, Shattuck, Turner, and Hamby in young adults. The best model depended on the outcome used as the original ACE questionnaire was the best fit in predicting depression, but the revised models were the best predictors of anxiety and perceived physical health. Future studies should continue to investigate whether these new items continue to improve the usefulness of the ACE scale or whether these items become less salient across the life span.
Comparative study on clinical results of arthroscopic repair of anteroinferior, superior, and combined glenoid labral tear
Authors: Zhu Meng , Chen Jerry Yongqiang , Chong Hwei Chi , Cheng Paul Chang Chee , Tjoen Denny Lie Tijauw
Published: March 2018

Background:

The purpose of this prospective study is to compare and correlate the clinical results of arthroscopic repair of a combined anteroinferior and superior labral lesion with those of an isolated anteroinferior labral lesion or type II superior labral tear from anterior to posterior (SLAP) lesion.

Methods:

A comparative study involving patients who underwent arthroscopic labral repairs in a tertiary hospital between 2010 and 2014 was conducted. A total of 96 patients were divided into three groups: Group A consisted of 61 patients with the anteroinferior labral lesion, group B consisted of 16 patients with the type II SLAP lesion, and group C consisted of 19 patients with the combined anteroinferior and superior labral lesion. Patient demographics, preoperative and postoperative pain scores, shoulder functional scores (Constant Shoulder Score, UCLA (University of California at Los Angeles) Shoulder Score, and Oxford Instability Score), and shoulder ranges of motion were measured and compared.

Results:

Except that patients from group B were generally older (28.8 vs. 22.2 for group A and 22.0 for group C, p = 0.04) at the time of surgery, no significant differences exist among the three groups in patient demographics and relevant clinical data. Preoperative and 2-year postoperative clinical outcomes, as well as the improvements, were comparable among the three groups. Low failure rates were observed for all three groups (6% vs. 10% vs. 11%, p = 0.999).

Conclusions:

Patients with the type II SLAP lesion underwent surgery at an older age. With appropriate surgical procedures, equivalent postoperative results can be expected for combined anteroinferior and superior labral lesion repair compared to isolated labral lesion repair.
Safety and Efficacy of Dolutegravir Plus Rilpivirine in Treatment-Experienced HIV-Infected Patients: The DORIVIR Study
Authors: Palacios Rosario , Mayorga M. , González-Domenech C. M. , Hidalgo-Tenorio C. , Gálvez C. , Muñoz-Medina L. , de la Torre J. , Lozano A. , Castaño M. , Omar M. , Santos Jesús
Published: March 2018

Objectives:

To analyze the efficacy and safety of dolutegravir/rilpivirine (DTG/RPV) in HIV-infected patients who switched from any other antiretroviral therapy (ART).

Methods:

Open-label, multicenter study including patients who switched to DTG/RPV between February 2015 and February 2016. Efficacy (HIV RNA <50 copies/mL), adverse events, and metabolic changes at 24 weeks were analyzed.

Results:

A total of 104 participants were included, who switched for the following reasons: toxicity/intolerance (42.3%), convenience (27.8%), and drug interactions (17.3%). Prior regimens are protease inhibitor (56.7%), integrase strand transfer inhibitor (26.9%), and non-nucleoside reverse transcriptase inhibitor (16.3%). Efficacy at 24 weeks was 88.4% (intention to treat) and 96.8% (per protocol). Triglyceride levels were reduced, on average, by 12.7% and a mean decrease of 9.0% in the glomerular filtration rate was observed as well ( P values of .003 and .002, respectively), whereas total cholesterol, HDL cholesterol, LDL cholesterol, creatinine, and glutamic-pyruvic transaminase remained unchanged. No patient discontinued due to adverse events.

Conclusions:

Dolutegravir/RPV is effective and safe in long-term HIV-infected patients under any prior ART. Toxicity, convenience, and interactions were the main reasons for changing. At 24 weeks, the lipid profile improved with a decrease in triglycerides.
An Analysis of Individual Differences in Recognizing Monosyllabic Words Under the Speech Intelligibility Index Framework
Authors: Shen Yi , Kern Allison B.
Published: March 2018

Individual differences in the recognition of monosyllabic words, either in isolation (NU6 test) or in sentence context (SPIN test), were investigated under the theoretical framework of the speech intelligibility index (SII). An adaptive psychophysical procedure, namely the quick-band-importance-function procedure, was developed to enable the fitting of the SII model to individual listeners. Using this procedure, the band importance function (i.e., the relative weights of speech information across the spectrum) and the link function relating the SII to recognition scores can be simultaneously estimated while requiring only 200 to 300 trials of testing. Octave-frequency band importance functions and link functions were estimated separately for NU6 and SPIN materials from 30 normal-hearing listeners who were naïve to speech recognition experiments. For each type of speech material, considerable individual differences in the spectral weights were observed in some but not all frequency regions. At frequencies where the greatest intersubject variability was found, the spectral weights were correlated between the two speech materials, suggesting that the variability in spectral weights reflected listener-originated factors.
The Challenge of Evaluating the Oral Health Status of Older Persons in Latin America
Authors: León S. , De Marchi R.J. , Giacaman R.A. , Tôrres L.H.N. , Espinoza I. , Hugo F.N.
Published: March 2018

Knowledge Transfer Statement: This article provides an overview of the oral health status of older people from Latin American countries and the emergence of recent gerodontology research initiatives within the region.
An Alternative Method of Endoscopic Intrasphenoidal Vidian Neurectomy
Authors: Zhao Changqing , Ji Yongjin , An Yunfang , Xue Jinmei , Li Qingfeng , Suo Limin , Hou Ran , Zhang Yanting , Geng Zhigang , Shen Huimei , Ren Jianjun , Yang Pingchang
Published: March 2018

Objective

To develop an easy surgical approach to facilitate clinical management.

Study Design

A novel transnasal endoscopic 3‐step surgical method for vidian neurectomy was designed and tried in 91 cases with a mild‐to‐severe degree of allergic and nonallergic rhinitis refractory to routine medical therapy.

Setting

Endoscopic vidian neurectomy requires accurate localization of the vidian canal. However, it is not easy to localize during surgery because of its deep location and the complex anatomy of the pterygopalatine fossa.

Subjects and Methods

This technique consists of 3 steps, including transnasal endoscopic perforation of the anterior wall of the sphenoidal sinus as the first step and removal of the anterior wall until the exposure of the vidian canal in the junction between the anterior wall and the floor of the sphenoid sinus as the second step. The last step is the accurate resection and cauterization of the vidian nerve. In some cases in which the sphenoid sinus developed well with a big lateral space, an extended procedure of posterior ethmoidectomy was included to allow good exposure of the vidian canal.

Results

Using this technique, successful endoscopic vidian neurectomy in this series of patients was confirmed by both histology and Schirmer test, showing its distinct advantages of easy localization of the vidian canal and less risk of injury to the nerve and vessel bundles within the pterygopalatine fossa.

Conclusion

Taken together, this novel 3‐step procedure of endoscopic vidian neurectomy plus an extended procedure guarantees good exposure of the vidian canal and therefore accurate vidian neurectomy.
From the Parents’ Perspective: The Think College Experience in Rural Vermont
Authors: Yuan Susan J. , Ryan Susan M. , Dague E. Bryan
Published: March 2018

Through qualitative interviews, perspectives of parents of students who were in the first 2 years of the Think College Program at University of Vermont and Johnson State College were explored, thereby identifying expectations, academic and social aspects, and experiences of their children as college members. Previous experience of these students in inclusive educational environments influenced parent perceptions. Parents described efforts to support the students during college, from financing and transportation to academic coaching and accommodating lessons. They discussed hopes for employment, and evolving perceptions of their own roles in relation to the future lives of their adult sons or daughters.
RETRACTED ARTICLE: Fabrication of a microfluidic device for studying the in situ drug-loading/release behavior of graphene oxide-encapsulated hydrogel beads
Authors: Veerla Sarath Chandra , Kim Da Reum , Yang Sung Yun
Published: March 2018

Background

Controlled drug delivery system is highly important for not only
prolonged the efficacy of drug but also cellular development for tissue
engineering. A number of biopolymer composites and nanostructured carriers
behave been used for the controlled drug delivery of therapeutics. Recently, in
vitro microfluidic devices that mimic the human body have been developed for
drug-delivery applications.

Methods

A microfluidic channel was fabricated via a two-step process: (i)
polydimethyl siloxane (PDMS) and curing agent were poured with a 10:2 mass ratio
onto an acrylic mold with two steel pipes, and (ii) calcium alginate beads were
synthesized using sodium alginate and calcium chloride solutions. Different
amounts (10, 25, 50 μg) of graphene oxide (GO) were then added by Hummers
method, and studies on the encapsulation and release of the model drug,
risedronate (Ris), were performed using control hydrogel beads (pH 6.3),
GO-containing beads (10GO, 25GO and 50GO), and different pH conditions. MC3T3
osteoblastic cells were cultured in a microchannel with Ris-loaded GO-hydrogel
beads, and their proliferation, viability, attachment and spreading were
assessed for a week.

Results

The spongy and textured morphology of pristine hydrogel beads was
converted to flowery and rod-shaped structures in drug-loaded hydrogel beads at
reduced pH (6.3) and at a lower concentration (10 μg) of GO. These latter 10GO
drug-loaded beads rapidly released their cargo owing to the calcium phosphate
deposited on the surface. Notably, beads containing a higher amount of GO (50GO)
exhibited an extended drug-release profile. We further found that MC3T3 cells
proliferated continuously in vitro in the microfluidic channel containing the
GO-hydrogel system. MTT and live/dead assays showed similar proliferative
potential of MC3T3 cells. Therefore, a microfluidic device with microchannels
containing hydrogel beads formulated with different amounts of GO and tested
under various pH conditions could be a promising system for controlled drug
release.

Conclusions

The GO and drug (risedronate, Rig) were directed loaded into a
hydrogel placed in a microchannel. Through interactions such as hydrogen bonding
between Go and the Rig-loaded GO-hydrogel beads, the bead-loaded microfluidic
device supported MC3T3 proliferation and development as osteoblast without
additional osteogenic differentiation supplements.
Lithobates catesbeianus(American Bullfrog) oocytes: a novel heterologous expression system for aquaporins
Authors: Kabutomori J. , Beloto-Silva O. , Geyer R. R. , Musa-Aziz R.
Published: March 2018

Xenopus laevis oocytes are a valuable tool for investigating the function of membrane proteins. However, regulations around the world, specifically in Brazil, render the import of Xenopus laevis frogs impractical, and, in some cases, impossible. Here, as an alternative, we evaluate the usefulness of the North American aquatic bullfrog Lithobates catesebeianus, which is commercially available in Brazil, for the heterologous expression of aquaporin (AQP) proteins. We have developed a method that combines a brief collagenase treatment and mechanical defolliculation for isolating individual oocytes from Lithobates ovaries. We find that they have a similar size, shape, and appearance to Xenopus oocytes and can tolerate and survive following injections with cRNA or water. Furthermore, surface biotinylation, western blot analysis, and measurements of osmotic water permeability (Pf) show that Lithobates oocytes can express AQPs to the plasma membrane and significantly increase the Pf of the oocytes. In fact, the Pf values are similar to historical values gathered from Xenopus oocytes. Due to the presence of a mercury sensitive cysteine (Cys or C) in the throat of the water channel, the Pf of oocytes expressing human (h) AQP1, hAQP1FLAG [FLAG, short protein tag (DYKDDDDK) added to the N-terminus of AQP1], hAQP8, and rat (r) AQP9 was inhibited with the mercurial compound p-chloromercuribenzene sulfonate (pCMBS), whereas AQPs lacking this Cys—hAQP1C189S mutant [residue Cys 189 was replaced by a serine (Ser or S)] and hAQP7—were mercury insensitive. Contrary to previous studies with Xenopus oocytes, rAQP3 was also found to be insensitive to mercury, which is consistent with the mercury sensitive Cys (Cys 11) being located intracellularly. Thus, we consider Lithobates oocytes to be a readily accessible system for the functional expression and study of membrane proteins for international researchers who do not currently have access to Xenopus oocytes.
Vangl2 disruption alters the biomechanics of late spinal neurulation leading to spina bifida in mouse embryos
Authors: Galea Gabriel L. , Nychyk Oleksandr , Mole Matteo A. , Moulding Dale , Savery Dawn , Nikolopoulou Evanthia , Henderson Deborah J. , Greene Nicholas D. E. , Copp Andrew J.
Published: March 2018

Human mutations in the planar cell polarity component VANGL2 are associated with the neural tube defect spina bifida. Homozygous Vangl2 mutation in mice prevents initiation of neural tube closure, precluding analysis of its subsequent roles in neurulation. Spinal neurulation involves rostral-to-caudal “zippering” until completion of closure is imminent, when a caudal-to-rostral closure point, “Closure 5”, arises at the caudal-most extremity of the posterior neuropore (PNP). Here we used Grhl3Cre to delete Vangl2 in the surface ectoderm (SE) throughout neurulation and in an increasing proportion of PNP neuroepithelial cells at late neurulation stages. This deletion impaired PNP closure after the ∼25 somite stage and resulted in caudal spina bifida in 67% of Grhl3Cre/+Vangl2Fl/Fl embryos. In the dorsal SE, Vangl2 deletion diminished rostrocaudal cell body orientation, but not directional polarisation of cell divisions. In the PNP, Vangl2 disruption diminished mediolateral polarisation of apical neuroepithelial F-actin profiles and resulted in eversion of the caudal PNP. This eversion prevented elevation of the caudal PNP neural folds, which in control embryos is associated with formation of Closure 5 around the 25 somite stage. Closure 5 formation in control embryos is associated with a reduction in mechanical stress withstood at the main zippering point, as inferred from the magnitude of neural fold separation following zippering point laser ablation. This stress accommodation did not happen in Vangl2-disrupted embryos. Thus, disruption of Vangl2-dependant planar polarized processes in the PNP neuroepithelium and SE preclude zippering point biomechanical accommodation associated with Closure 5 formation at the completion of PNP closure.
AutoCAD Mechanical
Authors: Бабенко Вера , Babenko Vera , Мухина Оксана , Mukhina Oksana
Published: March 2018

The tutorial dedicated to 2D modeling in recent versions of AutoCAD Mechanical, which is a CAD software for automation of design work in mechanical engineering.
Ability to develop design and technical documentation in the production, to perform the necessary calculations in accordance with GOST ESKD in professional activities with the use of co-time computer technologies – is the main professional competence that is formed when studying disciplines "Descriptive geometry, engineering and computer graphics".
AutoCAD Mechanical automate standard design tasks such as creating components, mechanisms, dimensions and specification, supports international standards for design drawings, includes a library of standard parts, numbering several hundred thousand items at the eighteen international standards, so in the engineering directions of students preparation in the universities would be more appropriately dealt CAD AutoCAD Mechanical instead of the base AutoCAD for engineering and computer graphics.
The tutorial describes the basics of working in AutoCAD Mechanical graphical system, provides description of the system structure, dashboards, actions, commands of 2D modeling.
The tutorial contains examples of creating engineering drawings with step-by-step implementation and detailed illustrations that will help beginning users to master modern technologies of drawings preparation. Having studied the material and mastered the methods of making drawings, stated in the manual, users will learn how to create and edit drawings; use object properties and layers as means of grouping and selecting graphical elements in the drawing and project documentations standardization for collective development; to create drawings using a generator shaft; for Assembly drawings and create BOM; save drawings in different formats and print them.
The textbook can be useful as a practical guide to students, learning AutoCAD Mechanical graphical system; teachers for the learning process; for novice users, owning the basics of engineering drawing and having initial experience in AutoCAD; engineers-mechanical engineers working in the CAD.
Medication-related osteonecrosis of the jaw (MRONJ): realities, risks and responsibilities
Authors: Rasaratnam Lakshmi , Kelleher Martin , Taylor Sarah
Published: March 2018

Considerable concern and confusion exists about Medication-Related OsteoNecrosis of the Jaw (MRONJ) which can be a painful, prolonged and debilitating condition caused by the death of jaw bone. The most common class of drugs causing this rare problem is the bisphosphonate group of drugs, which resulted in the term Bisphosphonate-Related OsteoNecrosis of the Jaw previously being given the acronym BRONJ.

CPD/Clinical Relevance: This article will help to update healthcare practitioners on assessing the realistic risks of patients developing MRONJ. It offers some ideas on reducing those risks in a practical way.
The impact of diabetes on treatment in general dental practice
Authors: Yeung Vinson , Chandan Joht
Published: March 2018

Diabetes is a chronic disease currently known to affect at least 5% of the UK's population and is expected to continue to increase in prevalence. The disease has significant effects on the immune system and increases inflammatory responses.

Diabetes affects various parts of everyday general dental practice including: the altered host-pathogen relationship on periodontal disease and its management; the dental pulp and, therefore, endodontics; and both wound and bony healing, thereby impacting surgical procedures.

Educating diabetes patients about the effects of the disease and associated risks to their treatment is important in patient management.

CPD/Clinical Relevance: Diabetes is a prevalent chronic disease in the UK and can adversely affect oral health and dental treatment outcome.
The risks of delayed oral cancer detection in primary care
Authors: Shah Paayal , Pandya Rishi , Mirza Tahir , Chan Chi-Hwa
Published: March 2018

Oral malignancy necessitates early detection for a better prognosis. Clinical presentation may vary, from a small mucosal lesion with benign clinical features to a large ulcerated mass with considerable local destruction.

The case of a 46-year-old patient presenting to a dental access centre with upper quadrant jaw pain, parasthaesia and unexplained tooth mobility is discussed. Delay in recognizing key features suggestive of sinister pathology led to a seven-week delay in referral of an aggressive, rare, odontogenic malignancy; ameloblastic carcinoma. The patient underwent extensive surgery with adjunctive radiotherapy.

CPD/Clinical Relevance: Odontogenic malignancy can cause rapid and extensive local invasion with a high potential for local or regional spread. Maxillary tumours often present with late, non-specific symptoms, thus must be detected early.
A contemporary approach to the provision of tooth-supported fixed prostheses part 2: fixed bridges where the abutment teeth require minimal or no preparation
Authors: Ibbetson Richard
Published: March 2018

Fixed tooth replacement is a central part of prosthodontic care for patients. The approach and options for treatment have changed due to the decrease in dental disease in the population and the impact of the osseo-integrated implant. Despite the impact of the dental implant, there remain indications for the use of tooth-supported fixed prostheses. The impact of improving oral health, the continued developments in resin-retained bridgework and the dental implant have reduced the indications for fixed prostheses retained by crowns. The last 30 years have seen a simplification in the design of fixed bridgework and this article describes the contemporary approach to this treatment modality. The second of this two part series discusses the influence of patient choice and the use of fixed bridges requiring little or no tooth preparation.

CPD/Clinical Relevance: To assist the reader in appreciating the principles of design for fixed bridgework whether supported by crowns or resin retainers.