bluuebunny/crossref_metadata_2025 huggingface dataset:
E-readers and the death of the book: Or, new media and the myth of the disappearing medium
Authors: Ballatore Andrea , Natale Simone
Published: May 2015

The recent emergence of e-readers and electronic books (e-books) has brought the death of the book to the centre of current debates on new media. In this article, we analyse alternative narratives that surround the possibility of the disappearance of print books, dominated by fetishism, fears about the end of humanism and ideas of techno-fundamentalist progress. We argue that in order to comprehend such narratives, we need to inscribe them in the broader history of media. The emergence of new media, in fact, has often been accompanied by narratives about the possible disappearance of older media: the introduction of television, for instance, inspired claims about the forthcoming death of film and radio. As a recurrent narrative shaping the reception of media innovation, the myth of the disappearing medium helps us to make sense of the transformations that media change provokes in our everyday life.
Branding politics: Emotion, authenticity, and the marketing culture of American political communication
Authors: Serazio Michael
Published: May 2015

This article examines and critiques the logic and practices of branding that inform contemporary American political campaigns within the context of ethical surplus, sign value versus use value, emotion and reason, and the tension of authenticity and cynicism. The original research is based upon 38 one-on-one, in-depth interviews with political consultants, including media strategists, communication directors, and advertising producers who are involved in the encoding and cultural production of political discourse. The qualitative findings illuminate a professional ideology among these elite practitioners that obfuscates the pursuit of power by strategizing texts that involve emotional evocation rather than rational deliberation and embed candidates within signifiers of and proxies for authenticity. These efforts are intended to strike a disinterested, non-instrumental pose on behalf of the “branded candidates” they represent.
The relationship between the polymorphisms of the CYP17A1 gene and hypertension: A meta-analysis
Authors: Dai Chuan-Fang , Xie Xiang , Ma Yi-Tong , Yang Yi-Ning , Li Xiao-Mei , Fu Zhen-Yan , Liu Fen , Chen Bang-Dang , Gai Min-Tao
Published: May 2015

Objective:

With the development of genome-wide association studies (GWAS) concerning hypertension, a growing number of susceptibility genes related to hypertension have been revealed. Subsequently, several studies have investigated the association between CYP17A1 rs1004467 heritable variation and hypertension; however, the results have been inconsistent. In this study, a meta-analysis was performed to assess the association between the CYP17A1 rs1004467 polymorphism and hypertension risk.

Methods:

The PubMed, ISI Web of Science and Embase databases as well as China Wanfang, Weipu and the Chinese Journal Full-text Database were used to retrieve all publications from 2005 to 2013 related to case-control studies that reported a link between the risk factors for hypertension and the CYP17A1 polymorphism. All association studies were identified, and a meta-analysis was conducted using the RevMan 5.0 estimate for odds ratios (ORs) to determine whether the A allele predicts hypertension outcomes.

Results:

Three articles including five studies (totaling 4495 patients and 3529 controls) were identified. The overall effect suggested that rs1004467 was significantly associated with hypertension (OR=1.22, 95%CI 1.08–1.38, p=0.001).

Conclusions:

The present meta-analysis confirmed the significant association between a polymorphism of the CYP17A1 gene and hypertension susceptibility. The CYP17A1 A allele should be considered a risk factor for hypertension.
A psychological intervention for smoking cessation delivered as treatment for smokers with chronic obstructive pulmonary disease
Authors: Yap Su Yin , Lunn Sarah , Pang Elizabeth , Croft Carla , Stern Myra
Published: May 2015

This pilot study investigated the benefits of adjunctive psychological intervention for smokers accessing standard smoking cessation interventions. Chronic obstructive pulmonary disease (COPD) smokers attending a smoking cessation service were offered up to 12 adjunctive clinical psychology sessions. Baseline data included demographics, smoking history, and disease severity. Outcomes included attendance and quit rate. In all, 59 patients with moderate COPD were referred. Of the 20 patients who attended training sessions, 7 (35%) were relapse prevention referrals and 13 (65%) were current smokers. Of the seven relapse prevention referrals, six (86%) maintained their quit, 2 of 13 (15%) of the current smoker group maintained a 28-day quit and 3 of 13 (23%) of current smokers reduced their tobacco intake. For COPD smokers with a heavy smoking history and multiple past quit attempts, there was insufficient evidence to show that additional psychological intervention leads to higher quit rates. Significant barriers to quitting and complex medical and psychosocial needs were identified in this group, suggesting that the current ‘one-size-fits-all’ approach to smoking cessation may not be sufficient to meet the needs of such a complex group.
The effect of physical training on the N-methyl-N-nitrosourea-induced mammary carcinogenesis of Sprague–Dawley rats
Authors: Malicka Iwona , Siewierska Katarzyna , Pula Bartosz , Kobierzycki Christopher , Haus Dominik , Paslawska Urszula , Cegielski Marek , Dziegiel Piotr , Podhorska-Okolow Marzena , Wozniewski Marek
Published: May 2015

The impact of physical activity on carcinogenesis has been demonstrated in many studies. Taking into account the discrepant results of physical exercise on the cell proliferation and apoptosis of breast cancer, we aimed to examine the impact of physical training on N-methyl- N-nitrosourea-(MNU)-induced mammary carcinogenesis. Fifty female rats were divided into four groups according to the intensity of physical activity they undertook. The number of developed tumors, tumor volume, and histopathological diagnoses were noted. Apoptosis and cell proliferation were studied by the number of TUNEL-positive and Ki-67-expressing cells. We demonstrated a statistically significant decrease in the tumor number between all trained groups and the control group. The results were most pronounced in the group with a moderate intensity of training. Moreover, we showed a decrease in tumor volume as training intensity increased, though the differences were not statistically significant. The mean number of TUNEL-positive cancer cells was significantly higher in the training groups than in the control group. These data suggest that physical training, especially of moderate intensity, may alleviate MNU-induced mammary carcinogenesis. The results could suggest that physical exercise-induced apoptosis may be a protective mechanism.
“Off-Label” Usage of Testicular Self-Examination (TSE): Benefits Beyond Cancer Detection
Authors: Rovito Michael J. , Leone James E. , Cavayero Chase T.
Published: May 2015

Testicular cancer (TCa) is the most common cancer among 15- to 34-year-old males. Treatments are highly effective, which help foster approximately 98% 5-year survival rate. There are very few known causal factors of the disease (e.g., cryptorchidism and family history), thus possibly limiting primary prevention methods. Secondary preventative measures, on the other hand, most notably testicular self-examination (TSE), are well-known and are promoted to help prevent late-stage diagnosis of TCa. However, debate ensues as to whether or not TSE provides any benefit. In light of a recent systematic review conducted by these authors assessing the effectiveness of TSE promotion interventions, we propose that the behavior can serve as a tool not just for detection of TCa, but other male-specific urogenital health concerns, including varicoceles, hydroceles, among others. Furthermore, we suggest that TSE can also help foster informed decision-making skills among males with regard to health concerns and treatment options. However, our advocacy is in direct conflict with U.S. Preventive Services Task Force’s influential “D” rating of TSE and others who recommend against performing TSE. This article offers an overview of the dispute over TSE’s purpose and net benefit. We conclude that TSE is a behavior that is beneficial beyond detecting cancer. These proposed “off-label” uses of the procedure make for an effectual means to promote testicular health, self-awareness, and wellness among males. Recommendations for future research and advocacy are presented to the academy.
Relationship Between Aerobic Fitness, the Serum IGF-1 Profiles of Healthy Young Adult African American Males, and Growth of Prostate Cancer Cells
Authors: Sridhar Rajagopalan , Bond Vernon , Dunmore-Griffith Jacquelyn , Cousins Valerie M. , Zhang Renshu , Millis Richard M.
Published: May 2015

The growth of prostate tumors is mediated by the bioavailability of androgens and insulin-like growth factors. This study tested the hypothesis that healthy young adult African American men exhibiting low aerobic capacity (fitness) have serum insulin-like growth Factor-1 (IGF-1) and testosterone levels that promote growth of prostate cancer cells. A cross-sectional data research design was used to study groups of 18- to 26-year-old healthy men exhibiting low and moderate aerobic fitness, based on their peak oxygen consumption (VO2peak). The individual serum levels of IGF-1, IGF-1 binding protein-3 (IGFBP-3), and testosterone were measured. In vitro growth of androgen-dependent LNCaP prostate tumor cells was measured after incubation in culture medium fortified with each subject’s serum. Aerobic capacity was significantly greater in the moderate-fitness group than in the low-fitness group without an intergroup difference in body mass index. The serum IGF-1 concentration was significantly higher in the low-fitness group in the absence of an intergroup difference in serum testosterone. The serum IGFBP-3 concentration was significantly lower in the low-fitness group. Prostate tumor cell growth was significantly greater in the cultures incubated in media containing the sera of the low-fitness group than in the sera of the moderate-fitness group. These findings suggest that moderate aerobic fitness in young adults may decrease the circulating levels of free IGF-1 and lower the potential to support growth of prostate cancer cells.
Combined percutaneous and transarterial devascularisation of juvenile nasopharyngeal angiofibroma with protection of internal carotid artery: A modification of the technique
Authors: Borota Ljubisa , Mahmoud Ehab , Nyberg Christoffer , Ekberg Tomas
Published: May 2015

Juvenile nasal angiofibroma (JNA) is a hypervascularised, benign, but locally aggressive tumour that grows in the posterior, upper part of the nasal cavity and invades surrounding anatomical structures. The treatment of choice is surgical removal, but complete resection of the tumour can be hampered because of profuse perioperative bleeding. Preoperative embolisation of the tumour has been proposed as an effective method for prevention of perioperative bleeding, thereby shortening of the time of the operation. In this report of five cases, we describe successful preoperative devascularisation of the tumour by applying a modified method of direct intratumoural injection of the liquid embolic agent Onyx combined with protection of the internal carotid artery. The control of bleeding during the embolisation and occlusion of the maxillary or sphenopalatine artery was achieved by using a bi-luminal balloon catheter. Such use of the dual-lumen catheter in treatment of JNA has not been reported so far in the medical literature.
What is the intention with skinny labels and second medical use patents?
Authors: Hayes Christopher
Published: May 2015

The impact of second medical use patents on skinny label generic launches was considered in Warner-Lambert Company, LLC v Actavis Group PTC EHF & Others [2015] EWHC 72 (Pat). The UK courts have had to decide whether a preliminary injunction should be granted to a patentee, where the patent is for a second medical use and the product to be launched has had the patented indication carved out of the label. In this case, the court held that an injunction should not be granted. The result is that generic companies considering launching with a skinny label may have less to fear from second medical use patents than previously thought.
Untangling research and practice: What Facebook’s “emotional contagion” study teaches us
Authors: boyd danah
Published: May 2015

Published in 2014, the Facebook “emotional contagion” study prompted widespread discussions about the ethics of manipulating social media content. By and large, researchers focused on the lack of corporate institutional review boards and informed consent procedures, missing the crux of what upset people about both the study and Facebook’s underlying practices. This essay examines the reactions that unfolded, arguing the public’s growing discomfort with “big data” fueled the anger. To address these concerns, we need to start imagining a socio-technical approach to ethics that does not differentiate between corporate and research practices.
NICE and general practice
Authors: Haslam Professor David
Published: May 2015

For ideas to make it in Greece 2500 years ago, they had to be good ones. Ideas were tested, through exhaustive debate, and if they succeeded they were celebrated. These ideas were so powerful that they still ring loudly through our society today – through our legal system, our theatre, our art, our architecture and arguably most effectively through science and medicine. It was into this tumult that Hippocrates was born and set down the principles of modern Western medicine. We know that Hippocrates gave the first recorded advice to physicians on the best way to treat patients. He understood the importance of observations and record-keeping to inform other physicians and improve care. These ideas are still fundamentally important in the practice of medicine. They are fundamental to the everyday work of GPs and they underpin the work of an organisation that, although only 16 years old, has its roots in the principles set down by Hippocrates: the National Institute for Health and Care Excellence, which – after a lifetime working as a GP – I am proud to chair.
Cytoreductive nephrectomy and its role in the present-day period of targeted therapy
Authors: Culp Stephen H.
Published: May 2015

The beneficial effect of cytoreductive nephrectomy on survival of patients with metastatic renal cell carcinoma in the immunotherapy era was based on two prospective randomized trials. Unfortunately, such evidence does not yet exist in the present-day period of targeted therapy. Despite this, cytoreductive nephrectomy remains integral in the multimodal management of patients with metastatic renal cell carcinoma. Multiple retrospective studies as well as data from prospective studies examining targeted therapy support the continued use of cytoreductive nephrectomy in the properly selected patient. Ongoing studies will hopefully fine-tune the role and timing of cytoreductive nephrectomy in the context of targeted therapy.
Performance of Cleared Blood Glucose Monitors
Authors: Klonoff David C. , Prahalad Priya
Published: May 2015

Cleared blood glucose monitor (BGM) systems do not always perform as accurately for users as they did to become cleared. We performed a literature review of recent publications between 2010 and 2014 that present data about the frequency of inaccurate performance using ISO 15197 2003 and ISO 15197 2013 as target standards. We performed an additional literature review of publications that present data about the clinical and economic risks of inaccurate BGMs for making treatment decisions or calibrating continuous glucose monitors (CGMs). We found 11 publications describing performance of 98 unique BGM systems. 53 of these 98 (54%) systems met ISO 15197 2003 and 31 of the 98 (32%) tested systems met ISO 15197 2013 analytical accuracy standards in all studies in which they were evaluated. Of the tested systems, 33 were identified by us as FDA-cleared. Among these FDA-cleared BGM systems, 24 out of 32 (75%) met ISO 15197 2003 and 15 out of 31 (48.3%) met ISO 15197 2013 in all studies in which they were evaluated. Among the non-FDA-cleared BGM systems, 29 of 65 (45%) met ISO 15197 2003 and 15 out of 65 (23%) met ISO 15197 2013 in all studies in which they were evaluated. It is more likely that an FDA-cleared BGM system, compared to a non-FDA-cleared BGM system, will perform according to ISO 15197 2003 (χ2 = 6.2, df = 3, P = 0.04) and ISO 15197 2013 (χ2 = 11.4, df = 3, P = 0.003). We identified 7 articles about clinical risks and 3 articles about economic risks of inaccurate BGMs. We conclude that a significant proportion of cleared BGMs do not perform at the level for which they were cleared or according to international standards of accuracy. Such poor performance leads to adverse clinical and economic consequences.
Patient Self-Management of Diabetes Care in the Inpatient Setting
Authors: Shah Arti D. , Rushakoff Robert J.
Published: May 2015

Self-management of diabetes by inpatients can be problematic. People with type 1 diabetes often prefer to self-manage their diabetes in the inpatient setting. We report the case of a patient admitted to the surgical service who was self-administering his home insulin, often without telling his nurse or physician. He was aiming for tight glycemic control, which resulted in life-threatening hypoglycemia. While patients can often self-manage their diabetes in the outpatient setting, inpatient management of diabetes is very different. Patients may not be familiar with common scenarios requiring adjustments of insulin therapy. Therefore, we recommend against self-management of diabetes in the hospital. However, the patients should be involved in discussions about management of their diabetes in the hospital to allay their concerns about changes made to their insulin regimens. An example of successful cooperative management is with use of protocols that allow continued use of insulin pumps in the hospital.
Surgical Management of Freiberg’s Infraction
Authors: Schade Valerie L.
Published: May 2015

Avascular necrosis of the second metatarsal head was first described by Freiberg in 1913. Conservative treatment includes nonsteroidal anti-inflammatory medication, reduced activity, padding, orthotics, and immobilization. Should conservative treatment fail, a wide variety of surgical procedures exist; however, the optimal procedure is unknown. This systematic review was undertaken to determine which surgical procedure allows for the best resolution of symptoms and return to activity. Included studies were restricted to articles published in English language peer-reviewed journals that consecutively enrolled patients of all ages, with Freiberg’s infraction of any stage, who underwent operative treatment, and had a mean follow-up of greater than or equal to 12 months duration. Eighty-five publications were identified, of which 38 (44.7%) met all the inclusion criteria. Surgical techniques and outcomes were grouped into joint sparing and joint destructive procedures. A total of 70 joint destructive procedures were performed with a combined mean follow-up time of 15.0 months. A greater than 70% resolution of pain and full return to activity was reported. A total of 257 joint sparing procedures were performed with a combined mean follow-up of 30.4 months. A greater than 90% resolution of pain and full return to activity was reported. Results of this systematic review reveal that the results of joint sparing procedures are reported more often and appear to have a better prognosis for symptom resolution and return to activity. Smillie stage was not consistently reported, making it difficult to determine its effect on procedure selection.

Level of Evidence: Therapeutic, Level IV: Systematic review of Level IV studies
Regional Contrasts in Consumers’ Attitudes and Behavior Following the BP Oil Spill
Authors: Susskind Alex M. , Bonn Mark A. , Lawrence Benjamin C. , Furr H. Leslie
Published: May 2015

In this paper, we examine how consumers’ reactions to the British Petrolium (BP) oil spill and their attitudes about the Gulf of Mexico as a tourism destination differ as a function of the respondents’ geographic location of residence and their past travel behavior. A survey conducted with 540 travelers and tourists, which began three weeks following the successful capping of the oil leak in the Gulf of Mexico, reveals that consumers’ reactions to the oil spill varied by geographic location and past travel behavior. In particular, consumers from the southeast region, when compared with the three other geographic regions we sampled, had more negative views regarding the oil spill on a number of dependent measures. We also found that individuals who traveled to Florida in the two years prior to the oil spill reported higher perceptions of environmental risk than those individuals who had not traveled to Florida during that same time frame.
Management of epididymo-orchitis in three different clinical settings: Streamlining pathways and improving care
Authors: Blach O , Ali A , Goubet S , Nawrocki J , Richardson D , Thomas P
Published: May 2015

Objective:

This study represents the first direct comparison of management of epididymo-orchitis (EO) by Accident and Emergency (A&E), Urology and Genito-Urinary Medicine (GUM) departments in a large tertiary care centre, and their compliance with international guidelines.

Methods:

Case notes of patients with EO who attended A&E, Urology and GUM between January and June 2014 were analysed retrospectively.

Results:

A total of 127 men were seen (median age: 33, range: 15–79). Forty-four attended A&E (median age: 35), 30 Urology (median age: 37), and 53 GUM (median age: 31). MSU was sent in 17/44 (38.6%) of A&E, 11/30(36.7%) of Urology, and 35/53(66%) of GUM patients. Fifty-three of 53 (100%) of GUM, 14/44 (31.8%) of A&E and four of 30 (13.3%) of Urology patients had chlamydia and gonorrhoea NAAT testing. Of these, 90.9% of A&E, 93.3% of Urology and 100% of GUM patients were prescribed antibiotics. Twelve A&E and one Urology patient were referred to GUM. Conversely, only three of 11 A&E and zero of five GUM patients aged over 50 were referred for urological follow-up.

Conclusion:

The management of EO, especially in younger men at risk of STIs by A&E and Urology, and older men at risk of urological problems by GUM, is an area for significant improvement. Closer co-operation between departments, unifying local management protocols, abandoning the traditional demographic divide, and ensuring effective referral pathways are essential to improving care.
Cost-effectiveness of stimulation of the sphenopalatine ganglion (SPG) for the treatment of chronic cluster headache: a model-based analysis based on the Pathway CH-1 study
Authors: Pietzsch Jan B. , Garner Abigail , Gaul Charly , May Arne
Published: May 2015

Background

In the recent Pathway CH-1 study, on-demand stimulation of the sphenopalatine ganglion (SPG) by means of an implantable neurostimulation system was proven to be a safe and effective therapy for the treatment of chronic cluster headache. Our objective was to assess the cost-effectiveness of SPG stimulation in the German healthcare system when compared to medical management.

Methods

Clinical data from the Pathway CH-1 study were used as input for a model-based projection of the cost-effectiveness of SPG stimulation through 5 years. Medical management as the comparator treatment was modeled on the basis of clinical events observed during the baseline period of CH-1. The costs of treatment were derived from a previously published cluster headache costing study and 2014 medication, neurostimulator, and procedure costs. We computed the 5-year incremental cost-effectiveness ratio (ICER) in euros per quality-adjusted life year (QALY), with costs and effects discounted at 3 % per year.

Results

SPG stimulation was projected to add 0.325 QALYs over the study period, while adding €889 in cost, resulting in a 5-year ICER of €2,736 per QALY gained. Longer follow-up periods, higher baseline attack frequency, and higher utilization of attack-aborting medications led to overall cost savings. SPG stimulation was found either cost-effective or cost-saving across all scenarios investigated in sensitivity analyses.

Conclusions

Our model-based analysis suggests that SPG stimulation for the treatment of chronic cluster headache, under the assumption of sustained therapy effectiveness, leads to meaningful gains in health-related quality of life and is a cost-effective treatment strategy in the German healthcare system.
Visible Thrombolysis Acceleration of a Nanomachine Powered by Light-Driving F0F1-ATPase Motor
Authors: Duan Xiaoxia , Liu Lifeng , Jiang Weijian , Yue Jiachang
Published: May 2015

We report on thrombolysis acceleration of a nanomachine powered by light-driving δ-subunit-free F0F1-ATPase motor. It is composed of a mechanical device, locating device, energy storage device, and propeller. The rotory δ-subunit-free F0F1-ATPase motor acts as a mechanical device, which was obtained by reconstructing an original chromatophore extracted from Rhodospirillum rubrum. We found that the bioactivity of the F0F1-ATPase motor improved greatly after reconstruction. The zeta potential of the nanomachine is about −23.4 mV. Cytotoxicity induced by the nanomachine was measured using cell counting kit (CCK)-8 assay. The A549 cells incubated with different fractional concentrations of the nanomachine within 48 h did not show obvious cytotoxicity. The locating device helps the nanomachine bind to the thrombi. Energy was easily stored by exposing the nanomachine to 600-nm-wavelength irradiation, which promoted activity of the motor. The rotation of the long propeller accelerated thrombolysis of a blood clot in vitro in the presence of urokinase (UK). This result was based on visual inspection and confirmed by a series of tests.
InteractiVenn: a web-based tool for the analysis of sets through Venn diagrams
Authors: Heberle Henry , Meirelles Gabriela Vaz , da Silva Felipe R , Telles Guilherme P , Minghim Rosane
Published: May 2015

Background

Set comparisons permeate a large number of data analysis workflows, in particular workflows in biological sciences. Venn diagrams are frequently employed for such analysis but current tools are limited.

Results

We have developed InteractiVenn, a more flexible tool for interacting with Venn diagrams including up to six sets. It offers a clean interface for Venn diagram construction and enables analysis of set unions while preserving the shape of the diagram. Set unions are useful to reveal differences and similarities among sets and may be guided in our tool by a tree or by a list of set unions. The tool also allows obtaining subsets’ elements, saving and loading sets for further analyses, and exporting the diagram in vector and image formats. InteractiVenn has been used to analyze two biological datasets, but it may serve set analysis in a broad range of domains.

Conclusions

InteractiVenn allows set unions in Venn diagrams to be explored thoroughly, by consequence extending the ability to analyze combinations of sets with additional observations, yielded by novel interactions between joined sets. InteractiVenn is freely available online at: www.interactivenn.net.
Sex chromosome-to-autosome transposition events counter Y-chromosome gene loss in mammals
Authors: Hughes Jennifer F , Skaletsky Helen , Koutseva Natalia , Pyntikova Tatyana , Page David C
Published: May 2015

Background

Although the mammalian X and Y chromosomes evolved from a single pair of autosomes, they are highly differentiated: the Y chromosome is dramatically smaller than the X and has lost most of its genes. The surviving genes are a specialized set with extraordinary evolutionary longevity. Most mammalian lineages have experienced delayed, or relatively recent, loss of at least one conserved Y-linked gene. An extreme example of this phenomenon is in the Japanese spiny rat, where the Y chromosome has disappeared altogether. In this species, many Y-linked genes were rescued by transposition to new genomic locations, but until our work presented here, this has been considered an isolated case.

Results

We describe eight cases of genes that have relocated to autosomes in mammalian lineages where the corresponding Y-linked gene has been lost. These gene transpositions originated from either the X or Y chromosomes, and are observed in diverse mammalian lineages: occurring at least once in marsupials, apes, and cattle, and at least twice in rodents and marmoset. For two genes - EIF1AX/Y and RPS4X/Y - transposition to autosomes occurred independently in three distinct lineages.

Conclusions

Rescue of Y-linked gene loss through transposition to autosomes has previously been reported for a single isolated rodent species. However, our findings indicate that this compensatory mechanism is widespread among mammalian species. Thus, Y-linked gene loss emerges as an additional driver of gene transposition from the sex chromosomes, a phenomenon thought to be driven primarily by meiotic sex chromosome inactivation.
Slow release anti-fungal skin formulations based on citric acid intercalated layered double hydroxides nanohybrids
Authors: Perera Jayoda , Weerasekera Manjula , Kottegoda Nilwala
Published: May 2015

Background

During the past few decades, the occurrence of superficial fungal infections has rapidly increased. As the fungal infections take longer time to get cured, concepts such as designing drugs with extended persistence and controlled release have gained attention. In this context, nanotechnology has been identified as the latest technological revolution which has opened up new pathways for designing new therapeutic materials. Out of the many available nano-structures layered double hydroxides have gained increased scientific attention in applications as slow and controlled release drug formulations. This study focuses on the encapsulation of citric acid which has anti-fungal properties into a Mg-Al- layered double hydroxide (LDH) in order to be used as slow release topical skin formulations.

Results

Citrate ions were encapsulated into Mg-Al LDH using one step co-precipitation reaction. The successful intercalation of citrate ions into the layered structure has been proved referring to the expansion in the interlayer spacing as observed by the shift in the basal peak of the powder X-ray diffraction pattern. Fourier transform infra-red spectroscopy data suggests the change in the electron density around the carboxylate groups of the citrate ion thus providing evidences for formation of encapsulated hybrid composite. The resulting nanohybrid has been then, introduced into a general body cream formulation containing cocoa-butter. Both citrate LDH and the resulting body cream formulations demonstrated prolonged slow release characteristics up to 8 h in aqueous medium under different pH values (3, 4, and 5) compared to quick and fast release of pure citric acid. It was observed that the slow reelase was most efficient at low pH values. The encapsulation between the nano-layers and citrate ions are the key to the slow release characteristics. The body cream has been tested for the anti-fungal activity against three common Candida species (C. albicans, C. glabrata, C. tropicalis). The novel nanohybrid has shown an improved activity and slow release characteristics up to 48 h against the C. albicans and C. glabrata but not for C. tropicalis.

Conclusion

The study confirms that the citrate ion intercalated LDHs have the potential for use in future slow release antifungal drug formulation.
Existing joint erosions increase the risk of joint space narrowing independently of clinical synovitis in patients with early rheumatoid arthritis
Authors: Landewé Robert , Smolen Josef S , Florentinus Stefan , Chen Su , Guérette Benoît , van der Heijde Désirée
Published: May 2015

Introduction

Clinical synovitis is often associated with damage to bone and cartilage. Previous data have suggested that joint erosions (JE) are more prevalent than joint space narrowing (JSN) and that the two processes are partly independent of each other. The objective of this study was to evaluate whether the presence of JE in an individual joint can lead to development of JSN and if existing JSN leads to new onset of JE, in the absence of synovitis.

Methods

The Prospective Multi-Centre Randomised, Double-Blind, Active Comparator-Controlled, Parallel-Groups Study Comparing the Fully Human Monoclonal Anti-TNFα Antibody Adalimumab Given Every Second Week With Methotrexate Given Weekly and the Combination of Adalimumab and Methotrexate Administered Over 2 Years in Patients With Early Rheumatoid Arthritis (PREMIER) enrolled early rheumatoid arthritis (RA) patients who were randomized to one of three treatments: methotrexate (MTX), adalimumab (ADA), or ADA + MTX. All evaluable joints with JE and JSN measures at 26 and 52 weeks and synovitis assessments from week 26 to 52 were included. Synovitis was assessed every 2–8 weeks by swollen joint counts between weeks 26 and 52. Radiographs were taken at week 26 and 52. Two readers, blinded to time and sequence, scored 14 bilateral joints individually for JE and JSN. Multivariate logistic modeling was used to characterize the dependence of JE/JSN onset at 52 weeks. Analyses were performed based on treatment arm and were also performed within individual joints.

Results

JE and swelling were independently and comparably associated with onset of JSN at week 52. Assessment by individual joints indicated that existing JE, independent of swelling, was significantly associated with JSN onset in higher proportions of metatarsophalangeal (MTP; 7/10) than proximal interphalangeal (PIP; 1/8) or metacarpophalangeal (MCP; 1/10) joints. Treatment with ADA + MTX prevents JE/JSN progression independently of its ability to suppress synovitis and limits JE/JSN onset and progression in joints with existing damage.

Conclusions

Existing JE predisposes individual joints to development of JSN independently of synovitis in the same joint. Weight-bearing MTP joints with JE may be at increased risk for JSN when compared with MCPs and PIPs.

Trial registration

Clinicaltrials.gov NCT00195663. Registered 13 September 2005.
Cost-effectiveness of abatacept, rituximab, and TNFi treatment after previous failure with TNFi treatment in rheumatoid arthritis: a pragmatic multi-centre randomised trial
Authors: Manders Sofie HM , Kievit Wietske , Adang Eddy , Brus Herman L , Moens Hein J Bernelot , Hartkamp Andre , Hendriks Lidy , Brouwer Elisabeth , Visser Henk , Vonkeman Harald E , Hendrikx Jos , Jansen Tim L , Westhovens Rene , van de Laar Mart AFJ , van Riel Piet LCM
Published: May 2015

Introduction

For patients with rheumatoid arthritis (RA) whose treatment with a tumour necrosis factor inhibitor (TNFi) is failing, several biological treatment options are available. Often, another TNFi or a biological with another mode of action is prescribed. The objective of this study was to compare the effectiveness and cost-effectiveness of three biologic treatments with different modes of action in patients with RA whose TNFi therapy is failing.

Methods

We conducted a pragmatic, 1-year randomised trial in a multicentre setting. Patients with active RA despite previous TNFi treatment were randomised to receive abatacept, rituximab or a different TNFi. The primary outcome (Disease Activity Score in 28 joints) and the secondary outcomes (Health Assessment Questionnaire Disability Index and 36-item Short Form Health Survey scores) were analysed using linear mixed models. Cost-effectiveness was analysed on the basis of incremental net monetary benefit, which was based on quality-adjusted life-years (calculated using EQ-5D scores), and all medication expenditures consumed in 1 year. All analyses were also corrected for possible confounders.

Results

Of 144 randomised patients, 5 were excluded and 139 started taking abatacept (43 patients), rituximab (46 patients) or a different TNFi (50 patients). There were no significant differences between the three groups with respect to multiple measures of RA outcomes. However, our analysis revealed that rituximab therapy is significantly more cost-effective than both abatacept and TNFi over a willingness-to-pay range of 0 to 80,000 euros.

Conclusions

All three treatment options were similarly effective; however, when costs were factored into the treatment decision, rituximab was the best option available to patients whose first TNFi treatment failed. However, generalization of these costs to other countries should be undertaken carefully.

Trial registration

Netherlands Trial Register number NTR1605. Registered 24 December 2008.
Association of large intergenic noncoding RNA expression with disease activity and organ damage in systemic lupus erythematosus
Authors: Wu Yanfang , Zhang Feifei , Ma Jianyang , Zhang Xiaoyan , Wu Lingling , Qu Bo , Xia Shiwei , Chen Shunle , Tang Yuanjia , Shen Nan
Published: May 2015

Introduction

Despite growing evidence that large intergenic noncoding RNAs (lincRNAs) can regulate gene expression and widely take part in normal physiological and disease conditions, our knowledge of systemic lupus erythematosus (SLE)-related lincRNAs remains limited. The aim of this study was to detect the levels of four lincRNAs (ENST00000500949: linc0949, ENST00000500597: linc0597, ENST00000501992: linc1992, and ENST00000523995: linc3995) involved in innate immunity in the peripheral blood mononuclear cells (PBMCs) of patients with SLE and correlate these lincRNA levels with disease activity, organ damage, clinical features and medical therapies.

Methods

PBMCs were obtained from 102 patients with SLE, 54 patients with rheumatoid arthritis (RA) and 76 healthy donors. lincRNA expression levels were measured by real-time quantitative polymerase chain reaction. Disease activity was assessed using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) scores, and organ damage was evaluated with the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index.

Results

linc0949 and linc0597 were significantly decreased in patients with SLE compared with patients with RA and healthy control subjects. linc0949 was correlated with SLEDAI-2K score (r = −0.329, P = 0.0007), as well as with complement component C3 level (r = 0.348, P = 0.0003). The level of linc0949 was also reduced in patients with SLE who had the presence of cumulative organ damage. In addition, decreasing expression of linc0949 was associated with lupus nephritis. linc0949 expression significantly increased after treatment, whereas neither disease activity nor organ damage correlated with linc0597 expression.

Conclusions

Our results provide novel empirical evidence that linc0949 could be a potential biomarker for diagnosis, disease activity and therapeutic response in SLE.
Migration towards SDF-1 selects angiogenin-expressing bone marrow monocytes endowed with cardiac reparative activity in patients with previous myocardial infarction
Authors: Ascione Raimondo , Rowlinson Jonathan , Avolio Elisa , Katare Rajesh , Meloni Marco , Spencer Helen L , Mangialardi Giuseppe , Norris Caroline , Kränkel Nicolle , Spinetti Gaia , Emanueli Costanza , Madeddu Paolo
Published: May 2015

Introduction

Chemokine-directed migration is crucial for homing of regenerative cells to the infarcted heart and correlates with outcomes of cell therapy trials. Hence, transplantation of chemokine-responsive bone marrow cells may be ideal for treatment of myocardial ischemia. To verify the therapeutic activity of bone marrow mononuclear cells (BM-MNCs) selected by in vitro migration towards the chemokine stromal cell-derived factor-1 (SDF-1) in a mouse model of myocardial infarction (MI), we used BM-MNCs from patients with previous large MI recruited in the TransACT-1&2 cell therapy trials.

Methods

Unfractioned BM-MNCs, SDF-1-responsive, and SDF-1-nonresponsive BM-MNCs isolated by patients recruited in the TransACT-1&2 cell therapy trials were tested in Matrigel assay to evaluate angiogenic potential. Secretome and antigenic profile were characterized by flow cytometry. Angiogenin expression was measured by RT-PCR. Cells groups were also intramyocardially injected in an in vivo model of MI (8-week-old immune deficient CD1-FOXN1nu/nu mice). Echocardiography and hemodynamic measurements were performed before and at 14 days post-MI. Arterioles and capillaries density, infiltration of inflammatory cells, interstitial fibrosis, and cardiomyocyte proliferation and apoptosis were assessed by immunohistochemistry.

Results

In vitro migration enriched for monocytes, while CD34+ and CD133+ cells and T lymphocytes remained mainly confined in the non-migrated fraction. Unfractioned total BM-MNCs promoted angiogenesis on Matrigel more efficiently than migrated or non-migrated cells. In mice with induced MI, intramyocardial injection of unfractionated or migrated BM-MNCs was more effective in preserving cardiac contractility and pressure indexes than vehicle or non-migrated BM-MNCs. Moreover, unfractioned BM-MNCs enhanced neovascularization, whereas the migrated fraction was unique in reducing the infarct size and interstitial fibrosis. In vitro studies on isolated cardiomyocytes suggest participation of angiogenin, a secreted ribonuclease that inhibits protein translation under stress conditions, in promotion of cardiomyocyte survival by migrated BM-MNCs.

Conclusions

Transplantation of bone marrow cells helps post-MI healing through distinct actions on vascular cells and cardiomyocytes. In addition, the SDF-1-responsive fraction is enriched with angiogenin-expressing monocytes, which may improve cardiac recovery through activation of cardiomyocyte response to stress. Identification of factors linking migratory and therapeutic outcomes could help refine regenerative approaches.
In vitro culture and production of syringin and rutin in Saussurea involucrata (Kar. et Kir.) – an endangered medicinal plant
Authors: Kuo Chao-Lin , Agrawal Dinesh-Chandra , Chang Hung-Chi , Chiu Ya-Ting , Huang Chu-Peng , Chen Yi-Lin , Huang Shih-Hung , Tsay Hsin-Sheng
Published: May 2015

Background

Saussurea involucrata (Kar. et Kir.) commonly known as ‘snow lotus’ or ‘Xue Lian’ is an important plant in the traditional Chinese system of medicine. The plant contains flavonoids such as syringin and rutin. These compounds have been reported to be anti-rheumatic, anti-inflammatory and dilate blood vessels, lower blood pressure, prevent cardiovascular diseases, enhance immunity, and act as anti-aging, anti-cancer, and anti-fatigue agents. The species has become endangered due to the excessive collection of S. involucrata plants in the wild, slower plant growth and ecological destruction of natural habitats. There is a severe shortage of plant material, while the market demand is ever increasing. Hence, it is very important to apply tissue culture technique for plant propagation and production of the bioactive compounds of this species.

Results

Multiple shoot induction and proliferation in shoot base explants derived from in vitro raised seedlings of S. involucrata was achieved on 3/4 strength of Murashige and Skoog’s (MS) basal medium (MSBM) supplemented with 1.0 mg/L−1 BA and 1.5 mg/L−1 NAA. Rooting was induced in 100 % shoots cultured on 1/2X MSBM supplemented with 1.0 mg/L−1 IBA for one week and then transfer to auxin free medium. The plantlets could be acclimatized successfully by sachet technique and established in the greenhouse. Maximum callus induction and proliferation in leaf segments was achieved on 1/2X MSBM supplemented with 0.5 mg/L−1 BA, 0.5 mg/L−1 NAA, 0.4 % gelrite and on incubation at 20 °C. Container closures had an influence on the quality and quantity of callus and production of the active compounds. The HPLC analysis showed much higher syringin content in in vitro shoots and callus as compared to commercially available market crude drug.

Conclusion

The present study describes an in vitro culture protocol of Saussurea involucrata. The bioactive compounds, syringin and rutin could be produced through tissue culture technique without sacrificing the endangered Saussurea involucrata plants in the wild.
Inflammatory environment and oxidized LDL convert circulating human proangiogenic cells into functional antigen-presenting cells
Authors: Vinci Maria Cristina , Piacentini Luca , Chiesa Mattia , Saporiti Federica , Colombo Gualtiero I , Pesce Maurizio
Published: May 2015

The function of human circulating PACs has been described extensively. However, little focus has been placed on understanding how these cells differ in their functions in the presence of microenvironments mimicking vascular inflammation. We hypothesized that exposure to proinflammatory cytokines or the oxLDL, an autoantigen abundant in advanced atherosclerotic plaques, converts PACs into immune-modulating/proinflammatory cells. Hence, we examined the effect of oxLDL and inflammatory stimuli on their phenotype by use of a functional genomics model based on secretome and whole genome transcriptome profiling. PACs obtained from culturing a PBMC fraction in angiogenic medium were primed with DC differentiation cytokines and then exposed to proinflammatory cytokines or oxLDL. Under these conditions, PACs converted into APCs, expressed maturation markers CD80 and CD83, and showed an increased up-regulation of CD86. APCcy and APCox induced a robust T cell BrdU incorporation. Despite a similar ability to induce lymphocyte proliferation, APCcy and APCox differed for the secretory pathway and mRNA expression. Analysis of the differentially expressed genes identified 4 gene “clusters,” showing reciprocal modulation in APCcy vs. APCox, justifying, according to functional genomics analyses, a different putative function of the cells in antigen processing. Together, these data show that treatment with inflammatory cytokines or oxLDL converts human PAC phenotypes and functions into that of APCs with similar lymphocyte-activating ability but distinct maturation degree and paracrine functions.
Disruption of Zebrafish Follicle-Stimulating Hormone Receptor (fshr) But Not Luteinizing Hormone Receptor (lhcgr) Gene by TALEN Leads to Failed Follicle Activation in Females Followed by Sexual Reversal to Males
Authors: Zhang Zhiwei , Lau Shuk-Wa , Zhang Lingling , Ge Wei
Published: May 2015

Gonadotropins are primary hormones that control vertebrate reproduction. In a recent study, we analyzed the impacts of FSH and LH on zebrafish reproduction by disrupting FSH and LH-β genes (fshb and lhb) using transcription activator-like effector nuclease (TALEN) technology. Using the same approach, we successfully deleted FSH and LH receptor genes (fshr and lhcgr) in the present study. In contrast to the deficiency of its cognate ligand FSH, the fshr-deficient females showed a complete failure of follicle activation with all ovarian follicles arrested at the primary growth-previtellogenic transition, which is the marker for puberty onset in females. Interestingly, after blockade at the primary growth stage for varying times, all females reversed to males, and all these males were fertile. In fshr-deficient males, spermatogenesis was normal in adults, but the initiation of spermatogenesis in juveniles was retarded. In contrast to fshr, the deletion of the lhcgr gene alone caused no obvious phenotypes in both males and females; however, double mutation of fshr and lhcgr resulted in infertile males. In summary, our results in the present study showed that Fshr was indispensable to folliculogenesis and the disruption of the fshr gene resulted in a complete failure of follicle activation followed by masculinization into males. In contrast, lhcgr does not seem to be essential to zebrafish reproduction in both males and females. Neither Fshr nor Lhcgr deficiency could phenocopy the deficiency of their cognate ligands FSH and LH, which is likely due to the fact that Fshr can be activated by both FSH and LH in the zebrafish.