bluuebunny/crossref_metadata_2025 huggingface dataset:
The compensatory renin–angiotensin system in the central regulation of arterial pressure: new avenues and new challenges
Authors: Mendoza Alberto , Lazartigues Eric
Published: March 2015

Hypertension is a widespread condition that affects millions of people around the world and has a major impact in public health. The classic renin–angiotensin system is a complex system comprised of multiple peptides and pathways that have been the driver of drug development over the years to control hypertension. However, there are still patients whose hypertension is very difficult to control with current drugs and strategies, thus motivating further research in this field. In the past two decades, important discoveries have expanded our knowledge of this system and new pathways are emerging that are helping us understand the complex interaction taking place not only in the periphery, but also in the central nervous system where the renin–angiotensin system is also very active. A new arm, called the ACE2/Ang-(1-7)/Mas receptor axis, was shown to exert antihypertensive properties and serve as a counterbalance to the classic ACE/angiotensin II/AT1 receptor axis, in this way modulating or even counteracting the negative effects of angiotensin II in blood pressure regulation and water retention. Modulation of this new axis through ACE2 activation, ADAM17 regulation or AT1 receptor internalization are some of the novel avenues and challenges that have the potential to become a target for new drug research and development for the treatment of hypertension.
Cardiovascular disease research activity in the Middle East: a bibliometric analysis
Authors: Al-Kindi Sadeer , Al-Juhaishi Taha , Haddad Fadi , Taheri Shahrad , Abi Khalil Charbel
Published: March 2015

Objectives:

The Middle East has a high prevalence of noncommunicable chronic diseases. The objective of this article was to quantify the research activity in cardiovascular disease (CVD) in the Middle East over the last 10 years.

Methods:

A Medline search was conducted using medical subject headings and author affiliation to retrieve research articles published from the Middle East between 2003 and 2012 (inclusive).

Results:

Middle Eastern countries produced only 3% of the total number of CVD research articles in the world. However, the overall trend showed an increase in the number of articles over the years, mainly from Turkey and Iran. Within this region, the ratio of CVD to non-CVD publications was highest in Qatar (0.23). Lebanon ranked first in the number of CVD publications per million persons (PMP) averaging 194.2 publications PMP and Turkey ranked highest in the number of CVD publications per US$1000 gross domestic product (GDP) per capita averaging 954 CVD publications per US$1000 GDP per capita.

Conclusions:

Although there has been a drive towards greater publication of CVD papers in the last decade, research activity in the Middle East still lags behinds developed countries. Greater productivity is anticipated to emerge to accompany the recent significant investment in research in Gulf countries.
Extra-articular scapular fractures: comparison of theoretical and actual treatment
Authors: Brandsema Berdien , Neuhaus Valentin , Gradl Gertraud , Ring David C
Published: March 2015

Background

Discrete radiographic thresholds of scapular fracture deformity proposed as a guide for when to utilize operative treatment are a matter of debate. The purpose of the present study was to determine how many patients would have received operative treatment according to these criteria and how many actually received operative treatment.

Methods

Three hundred and thirty patients with an extra-articular fracture of the scapula at two level 1 trauma centers were retrospectively analyzed. Glenopolar angle, translation, angulation and medial/lateral displacement were measured on computed tomogaphy scans or radiographs to determine the theoretical operative treatment recommendation according to Cole’s criteria.

Results

Sixty-two patients (19%) had one or more radiographic indications for operative treatment, half of them had more than 20 mm of lateral displacement, and one fourth of them had substantial translation. No patients had operative treatment of the scapular body. Two patients had operative treatment of an acromion fracture, neither of which met radiographic criteria for surgery.

Conclusions

At least in our centres, there is a striking discrepancy between theoretical and actual recommendations for surgery. There is clearly a need for more research to determine whether patients are being undertreated or whether the guidelines are too stringent.
Does Visceral Fat Estimated by Dual-Energy X-ray Absorptiometry Independently Predict Cardiometabolic Risks in Adults?
Authors: Sasai Hiroyuki , Brychta Robert J. , Wood Rachel P. , Rothney Megan P. , Zhao Xiongce , Skarulis Monica C. , Chen Kong Y.
Published: March 2015

Background:

Abdominal visceral fat, typically measured by computer tomography (CT) or magnetic resonance imaging (MRI), has been shown to correlate with cardiometabolic risks. The purpose of this study was to examine whether a newly developed and validated visceral fat measurement from dual-energy X-ray absorptiometry (DXA) provides added predictive value to the cross-sectional differences of cardiometabolic parameters beyond the traditional anthropometric and DXA adiposity parameters.

Method:

A heterogeneous cohort of 194 adults (81 males and 113 females) with a BMI of 19 to 54 kg/m2 participated in this cross-sectional study. Body composition was measured with a DXA densitometer. Visceral fat was then computed with a proprietary algorithm. Insulin sensitivity index (SI, measured by intravenous glucose tolerance test), blood pressures, and lipid profiles, and peak oxygen uptake were also measured as cardiometabolic risk parameters.

Results:

DXA-estimated visceral fat mass was associated with HDL cholesterol (regression coefficient [β] = −5.15, P < .01, adjusted R2 = .21), triglyceride (β = 26.01, P < .01, adjusted R2 = .14), and peak oxygen uptake (β = −3.15, P < .01, adjusted R2 = .57) after adjusting for age, gender, and ethnicity. A subanalysis stratifying gender-specific BMI tertiles showed visceral fat, together with ethnicity, was independently associated with SI in overweight men and moderately obese women (second tertile).

Conclusions:

Without requiring additional CT or MRI-based measurements, visceral fat detected by DXA might offer certain advantages over the traditional DXA adiposity parameters as means of assessing cardiometabolic risks.
The Accuracy and Efficacy of the Dexcom G4 Platinum Continuous Glucose Monitoring System
Authors: Nakamura Katherine , Balo Andrew
Published: March 2015

Background:

The purpose of this study was to evaluate the accuracy and efficacy of Dexcom G4 Platinum CGM System.

Methods:

Seventy-two subjects enrolled at 4 US centers; 61% were male; 83% had T1DM and17% had T2DM. Subjects wore at least 1 system for up to 7 days. Subjects participated in a total of 36 hours in the clinic to contribute YSI reference glucose measurements with venous blood draws every 15 minutes on study Day 1, Day 4, and Day 7.

Results:

The overall mean absolute relative difference (ARD) versus YSI was 13% with a median of 10%. Precision ARD was 9% ± 4% between 2 sensors with a 7% coefficient of variation. The mean ARD versus SMBG was 14% with a median of 11%. One hundred two (94%) sensors lasted 7 days and the systems displayed 97% of their expected glucose readings in average. The time spent in low CGM readings during nighttime hours decreased from the first night use to the 6th night ( P < .001) with a small difference in average CGM glucose from 147 ± 40 mg/dL to 166 ± 62 mg/dL. There were no serious adverse events or infectious complications reported.

Conclusions:

The study showed the Dexcom G4 Platinum CGM System is one of the most accurate CGMs. The significant reduction in nocturnal time spent in a hypoglycemic state observed during this study suggests that a longer term study of CGM use, especially nocturnal use, could be beneficial for patients with hypoglycemia unawareness.
Impaired Femoral Vascular Compliance and Endothelial Dysfunction in 30 Healthy Male Soccer Players
Authors: Cioni Gabriele , Berni Andrea , Gensini Gian Franco , Abbate Rosanna , Boddi Maria
Published: March 2015

Background:

Despite beneficial effects of physical activity on cardiovascular risk, discordant data on elite athletes (high atherosclerotic damage in activity comprising strenuous exertion) and retired sportsmen are reported in the literature.

Hypothesis:

We hypothesize that long-lasting daily physical activity could affect the morphology and function of the carotid and femoral vessel walls differently, as assessed in elite male athletes aged 20 to 30 years compared with age- and sex-matched healthy controls.

Study Design:

Retrospective case-control study.

Level of Evidence:

Level 3.

Methods:

Sixty male subjects (30 athletes and 30 controls) underwent medical examination for ankle brachial index, augmentation index (AIX) and AIX corrected for heart rate (AIXr), peripheral arterial tonometry (PAT), and intima media thickness and pulse wave velocity assay at common carotid (carotid–intima media thickness [c-IMT], carotid–pulse wave velocity [c-PWv]) and femoral arteries (femoral–intima media thickness [f-IMT], femoral–pulse wave velocity [f-PWv]) assessed by ultrasonography using Doppler ultrasound.

Results:

Athletes showed a significantly lower heart rate (HR) at rest and a better lipid profile than controls. In athletes, c-PWv (5.87 ± 0.80 vs 6.62 ± 1.02 m/s, P = 0.001) and f-PWv (8.96 ± 1.29 vs 7.89 ± 1.39, P = 0.002) were, respectively, significantly lower and higher than values found in controls; accordingly, carotid AIX (4.03 ± 6.21 vs 7.81 ± 5.21, P = 0.003) and femoral AIX (8.56 ± 10.21 vs 6.09 ± 7.95, P = 0.042) were lower and higher than control values, even after correction for heart rate ( P = 0.03). On the other hand, IMT values were significantly higher in controls than in athletes (c-IMT, P < 0.0001; f-IMT, P < 0.0001). A positive significant correlation between HR and c-IMT and f-IMT ( r = 0.527, P < 0.001 and r = 0.539, P < 0.0001, respectively) and between HR and c-PWv ( r = 0.410, P = 0.01) was found when controls and athletes were considered as a whole group. Soccer players showed lower PAT values in comparison with controls ( P = 0.002).

Conclusion:

Elite sports positively affect c-IMT, f-IMT, and carotid PWv and AIX but not femoral PWv, AIX, AIXr, or PAT.

Clinical Relevance:

Physical activity affects vascular beds in elite athletes differentially, depending on the rate of superior or inferior limb involvement in different sports. In soccer players, physical activity has a protective effect on carotid and femoral vessel walls but worsens femoral arterial and endothelial function. These findings highlight how different results can be shown on carotid and femoral districts, when these vascular districts are differently stressed during sport activity.
Next Generation Mesenchymal Stem Cell (MSC)–Based Cartilage Repair Using Scaffold-Free Tissue Engineered Constructs Generated with Synovial Mesenchymal Stem Cells
Authors: Shimomura Kazunori , Ando Wataru , Moriguchi Yu , Sugita Norihiko , Yasui Yukihiko , Koizumi Kota , Fujie Hiromichi , Hart David A. , Yoshikawa Hideki , Nakamura Norimasa
Published: March 2015

Because of its limited healing capacity, treatments for articular cartilage injuries are still challenging. Since the first report by Brittberg, autologous chondrocyte implantation has been extensively studied. Recently, as an alternative for chondrocyte-based therapy, mesenchymal stem cell–based therapy has received considerable research attention because of the relative ease in handling for tissue harvest, and subsequent cell expansion and differentiation. This review summarizes latest development of stem cell therapies in cartilage repair with special attention to scaffold-free approaches.
Changes in Chondrogenic Progenitor Populations Associated with Aging and Osteoarthritis
Authors: Brady Kyla , Dickinson Sally C. , Hollander Anthony P.
Published: March 2015

Chondrogenic progenitor populations, including mesenchymal stem cells, represent promising cell-based transplantation or tissue engineering therapies for the regeneration of damaged cartilage. Osteoarthritis (OA) predominantly affects the elderly and is a leading cause of disability worldwide. Advancing age is a prominent risk factor that is closely associated with the onset and progression of the disease. Understanding the influence that aging and OA have on chondrogenic progenitor cells is important to determine how these processes affect the cellular mechanisms of the cells and their capacity to differentiate into functional chondrocytes for use in therapeutic applications. Here, we review the effect of age- and OA-related changes on the growth kinetics and differentiation potential of chondrogenic progenitor cell populations. Aging differentially influences the proliferative potential of progenitor cells showing reduced growth rates with increased senescence and apoptotic activity over time, while chondrogenesis appears to be independent of donor age. Cartilage tissue affected by OA shows evidence of progenitor populations with some potential for repair, however reports on the proliferative propensity of mesenchymal stem cells and their chondrogenic potential are contradictory. This is likely attributed to the narrow age ranges of samples assessed and deficits in definitively identifying donors with OA versus healthy patients across a wide scope of advancing ages. Further studies that investigate the mechanistic effects of chondrogenic progenitor populations associated with aging and the progression of OA using clearly defined criteria and age-matched control subject groups are crucial to our understanding of the clinical relevance of these cells for use in cartilage repair therapies.
The Challenge and the Promise of Bone Marrow Cells for Human Cartilage Repair
Authors: Chu Constance R.
Published: March 2015

The cartilage repair potential of bone marrow–derived stem cells has been well described. Harnessing this potential for human articular cartilage repair remains challenging. Accessing bone marrow repair cells through marrow stimulation techniques such as microfracture is readily achieved with generally good but inconsistent results. Animal and human studies show feasibility for ex vivo processing of bone marrow to isolate, concentrate, and culture mesenchymal stem cells. Nevertheless, it has been difficult to show consistent and clinically meaningful improvement using bone marrow cell preparations above what has been achieved with microfracture. Consequently, microfracture continues to be the simplest and most commonly used method to enhance repair of focal articular cartilage defects. Emerging preclinical work in the equine model suggests a role for enhancing marrow-stimulation techniques through the use of natural scaffolds such as autologous platelet enriched fibrin as well as optimization of joint biology through localized gene therapy to support cartilage repair. In contrast to joint replacement where inert materials of known mechanical properties are used, host biology determines the relative success, failure, and durability of cartilage repair. As such, development of personalized strategies to improve the quality and durability of bone marrow cell–based articular cartilage repair represent exciting new areas of inquiry. Continued advances in stem cell biology, scaffold technologies, and methods to delineate and enhance host biology, both systemically and within the joint, hold promise for harnessing the full power of bone marrow cells to facilitate cartilage repair and regeneration.
The role of adipokines in gestational diabetes mellitus
Authors: Al-Badri Marwa R. , Zantout Mira S. , Azar Sami T.
Published: March 2015

Gestational diabetes mellitus (GDM) is a complication of pregnancy that is characterized by impaired glucose tolerance with onset or first recognition during pregnancy. The reported prevalence of GDM varies between 0.6% and 20% of pregnancies depending on screening method, gestational age and the population studied. GDM is characterized by pancreatic β-cell function that is insufficient to meet the body’s insulin needs. Available evidence suggests that β-cell defects in GDM result from the same spectrum of causes that underline hyperglycemia in general, including autoimmune disease, monogenic causes and insulin resistance. Adipokines are proteins secreted from the adipocytes and are believed to have a metabolic influence. Our review suggests that, in GDM, various adipokines, mainly leptin and adiponectin, are dysregulated. These two adipokines might have both prognostic and pathophysiological significance in this disease.
Comparison of vertebroplasty using directional versus straight needle
Authors: Soon Wai Cheong , Mathew Ryan K , Timothy Jake
Published: March 2015

Background

Percutaneous vertebroplasty is a minimally invasive procedure that can be performed to treat pain and immobility associated with vertebral compression fractures. Previous studies have shown that a single injection can achieve adequate fill across the midline of the vertebral body.

Purpose

To compare the radiological outcomes of using a novel steerable needle with using a conventional, straight needle in unipedicular vertebroplasty.

Material and Methods

Data were collected from 19 patients who were operated at our institute between 1 September 2010 and 31 March 2011. Outcomes were measured in terms of radiological evidence of midline crossing of cement. The available pre- and postoperative pain scores and complications were reviewed. Student’s t-test was used to compare mean cement projection across the midline in both groups with P < 0.05 considered to be statistically significant

Results

Mean fill across the midline was significantly greater with the steerable needle (58%) compared with the straight needle (35%) ( P = 0.046). Cement leakage was higher with the steerable needle (44% versus 30%); however no clinical complications were reported in either group.

Conclusion

Percutaneous vertebroplasty using a directional needle is an excellent example of advancement and refinement in spinal surgery without increased clinical risk. Our results indicate that the novel technique can potentially provide better radiological outcomes when compared with a straight needle. A larger, randomized multicenter prospective trial would be valuable in confirming these findings.
Management of primary iliopsoas abscess in an immunocompetent patient followed by streptococcal toxic shock syndrome: A case report
Authors: Hirooka Nobutaka , Edo Naoki , Danbara Hisanori , Nishimura Hiroki , Obuchi Yasuhiro , Tanaka Yuji
Published: March 2015

Objectives:

Clinical diagnosis of iliopsoas abscess can be challenging, as this pathology often presents without obvious focal findings. Iliopsoas abscess should thus be a differential diagnosis for patients presenting with fever of unknown origin.

Patient and methods:

A 62-year-old healthy Japanese man showed primary iliopsoas abscess of Klebsiella pneumoniae complicated by shock after a complete course of treatment for streptococcal toxic shock syndrome. Successful treatment was achieved with culture-driven antibiotic selection and delayed drainage.

Results:

This case demonstrates the importance of identifying the causative microorganisms in iliopsoas abscess to guide therapy. The standard treatments for iliopsoas abscess are antibiotics and drainage of the abscess. Management of this case included successful antibiotic use along with delayed drainage.

Conclusion:

This case report advances the knowledge on the etiology of iliopsoas abscess and sheds light on the need for scientific development of a treatment strategy.
The role of peritoneal ultrafiltration in the treatment of refractory congestive heart failure
Authors: Samoni Sara , Petrucci Ilaria , Fumagalli Giordano , Tattanelli Costanza , Meola Mario , Palmarini Daniela , Donadio Carlo
Published: March 2015

Lesson

This case offers a starting point for a literature review on peritoneal ultrafiltration in refractory heart failure.
Systematic analysis of funding awarded to institutions in the United Kingdom for infectious disease research, 1997–2010
Authors: Head Michael G , Fitchett Joseph R , Moore David AJ , Atun Rifat
Published: March 2015

Summary

Objectives

This study aimed to assess the research investments made to UK institutions for all infectious disease research and identify the direction of spend by institution.

Design

Systematic analysis. Databases and websites were systematically searched for information on relevant studies funded for the period 1997–2010.

Setting

UK institutions carrying out infectious disease research.

Participants

None.

Main outcome measures

Twenty academic institutions receiving greatest sum investments across infection are included here, also NHS sites, Sanger Institute, Health Protection Agency and the Medical Research Council. We measured total funding, median award size, disease areas and position of research along the R&D value chain.

Results

Included institutions accounted for £2.1 billion across 5003 studies. Imperial College and University of Oxford received the most investment. Imperial College led the most studies. The Liverpool and London Schools of Tropical Medicine had highest median award size, whereas the NHS sites combined had many smaller studies. Sum NHS funding appears to be declining over time, whilst university income is relatively stable. Several institutions concentrate almost exclusively on pre-clinical research. In some areas, there is clearly a leading institution, e.g. Aberdeen and mycology research or UCL and antimicrobial resistance.

Conclusion

UK institutions carry out research across a wide range of infectious disease areas. This analysis can identify centres of excellence and help inform future resource allocation for research priorities. Institutions can use this analysis for establishing expertise within their groups, identifying external collaborators and informing local research strategy.
A case of Phoma fungal keratitis in a contact lens user
Authors: Kumar Periyasamy , Thomas Shery , Papagiannuli Efrosini , Hardman Susan C , Jenkins David , Prydal Jeremy
Published: March 2015

Lesson

Fungi of the genus Phoma are common plant pathogens and saprophytes and are rarely pathogenic to animals.
Gait Characteristics in Patients With Chronic Obstructive Pulmonary Disease
Authors: Nantsupawat Nopakoon , Lane Paige , Siangpraipunt Ornwadee , Gadwala Swetha , Nugent Kenneth
Published: March 2015

Background: Patients with chronic obstructive pulmonary disease (COPD) have reduced gait speeds and more frequent falls. We analyzed gait characteristics and fall risk in these patients using video recordings and questionnaires to determine if these patients had any quantitative changes in gait characteristics and to determine if screening for fall risk provided useful information. Methods: Patients with COPD who had participated in pulmonary rehabilitation completed a short history falls and the Activities-Specific Balance Confidence Scale questionnaire. They performed the Get Up and Go Test. Their typical gait was video recorded and analyzed with Dartfish software. Results: Fourteen patients completed this study. The mean age was 69.7 ± 6.0 years, and the mean forced expiratory volume in 1 second was 1.01 ± 0.38 L (36.9% ± 15.6% predicted). Three patients had a history of falls without significant injury. The mean Activities-Specific Balance Confidence Scale score was 91.8 ± 14.9, but the scores ranged from 10 to 100. Patients reported decreased balance confidence when “stepping onto or off an escalator while holding onto parcels.” The mean time in the Get Up and Go Test was 11.9 ± 2.0 seconds. Spatiotemporal parameters of gait included mean step length 0.65 ± 0.6 m, mean double support time 0.36 ± 0.05 seconds, mean double support time ratio 30.4% ± 3.1%, average free walking speed 65.3 ± 6.9 m/min, and number of steps per minute 100.4 ± 8.8. The speed was significantly slower and the double support time was significantly longer when compared with normal values. Conclusions: Most patients had good balance confidence scores. Their gait and balance were qualitatively normal using the Tinetti tools for assessment. Therefore, their risk for falls seems low. They had a reduced step length and increased time spent in double support, changes which might represent subtle adaptations to reduced balance.
Use Patterns and Unlabeled Uses of Target-Specific Oral Anticoagulants
Authors: Lin Shin-Yi , Do Lynn V. , Kayser Steve R. , Shin Jaekyu
Published: March 2015

Background: Target-specific oral anticoagulants (TSOAs) have advantages and disadvantages over warfarin, and they differ by indication, dosage adjustment, and drug interactions. Objective: The purpose of this retrospective cohort study is to determine use patterns and unlabeled uses of TSOAs. Methods: From July 1, 2012, to April 30, 2014, orders for warfarin, dabigatran, rivaroxaban, or apixaban in a tertiary medical center were included. Electronic medical records were reviewed to collect information regarding characteristics of the patients receiving these medications. Unlabeled use was defined as an indication or dose not approved by the US Food and Drug Administration. The percentage of orders for each study drug per month and the percentage of orders for each TSOA that contained an unlabeled use were calculated. Results: Of a total of 869 orders, 140 (16.1%) were for TSOAs (13 dabigatran, 97 rivaroxaban, and 30 apixaban orders). Compared with the first 4 months of the study period, the monthly percentage of orders for a TSOA increased by 2.5-fold in the last 4 months. Of the 3 TSOAs, only orders for dabigatran decreased (5.6% in July 2012 vs 0% in April 2014). Of the 140 TSOA orders, 28 (20.0 %) were unlabeled uses (3 unlabeled indications and 25 unlabeled dose), which included 16 unlabeled renally adjusted doses. The percentage of unlabeled uses did not significantly differ by TSOA. Conclusion: The use of TSOAs has increased and unlabeled uses are common. These data provide opportunities for quality improvement in the use of TSOA in clinical practice.
Pharmacy Technicians and Point of Care Testing
Authors: Keller Megan E. , Kelling Sarah E. , Bright David R.
Published: March 2015

Objective: As the practice of pharmacy continues to advance and involve nondispensing pharmacy services, point-of-care testing (POCT) has continued to demonstrate its usefulness as a tool and service in pharmacy. Of particular significance is the ability of POCT to assist clinical practice related to diabetes, cholesterol management, and anticoagulation. POCT can allow for certain laboratory results to be obtained within seconds to minutes, which can help direct care. Many components of POCT programs can involve pharmacy technicians to help enhance practice efficiency. The purpose of this review is to provide an overview of POCT devices commonly used in nondispensing pharmacy services and to describe the roles that pharmacy technicians may have in the POCT process. Data Sources: PubMed (1946-2014) was reviewed for relevant literature using terms such as “pharmacy technician” and “point of care testing.” Additionally, manufacturer information/websites of POCT products were reviewed for approval information and instructions for use. Study Selection and Data Extraction: Articles describing POCT completed in a pharmacy setting and/or roles of pharmacy technicians and related support staff in the POCT process were considered for inclusion. Data Synthesis: Several types of POCT devices for different uses common to the practice of pharmacy are reviewed. Additionally, strategies for collaboration between pharmacy technicians and pharmacists in the execution of a POCT program are described. Conclusion: Pharmacy technicians are well suited to participate in portions of the POCT process, and the involvement of pharmacy technicians may improve POCT efficiency.
Preparation of PEDOT/GO, PEDOT/MnO2, and PEDOT/GO/MnO2 nanocomposites and their application in catalytic degradation of methylene blue
Authors: Zhang Li , Jamal Ruxangul , Zhao Qin , Wang Minchao , Abdiryim Tursun
Published: March 2015

The nanocomposite materials of poly(3,4-ethylenedioxythiophene)/graphene oxide (PEDOT/GO), poly(3,4-ethylenedioxythiophene)/MnO2 (PEDOT/MnO2), and poly(3, 4-ethylenedioxythiophene)/graphene oxide/MnO2 (PEDOT/GO/MnO2) were successfully prepared by facile and template-free solution method. The structure and morphology of nanonanocomposites were characterized by Fourier transform infrared spectroscopy (FTIR), ultraviolet–visible absorption spectra (UV–vis), field emission scanning electron microscope (FESEM), X-ray diffraction (XRD), and energy-dispersive X-ray spectroscopy (EDX), respectively. The catalytic activities of nanocomposites were investigated through the degradation processes of methylene blue (MB) solution under dark, UV light, and nature sunlight irradiation, respectively. The results displayed that nanocomposites were successfully synthesized, and PEDOT/GO had higher conjugation length and doped degree than pure PEDOT. However, the introduction of MnO2 could lead to the reduction of conjugation length and doped degree in PEDOT/MnO2 and PEDOT/GO/MnO2 nanocomposites. The field emission scanning electron microscope (FESEM) analysis also showed that both MnO2 and GO had some effect on the morphology of nanocomposites. The catalytic activities of pure PEDOT and nanocomposites were in the order of PEDOT/GO/MnO2 > PEDOT/MnO2 > PEDOT/GO > pure PEDOT. Besides, the catalytic results also showed that the highest degradation efficiency of MB after 7 h occurred in the PEDOT/GO/MnO2 composite in three irradiation.
Nodular syphilitic scleritis masquerading as an ocular tumor
Authors: Shaikh Sufiyan I , Biswas Jyotirmay , Rishi Pukhraj
Published: March 2015

Background

Scleritis may be the initial or only presenting feature of systemic, autoimmune, or infectious disorders. Corticosteroids are the mainstay of treatment for immune-mediated scleritis. However, steroids could prove detrimental when used to treat infectious scleritis. Hence, infectious causes of scleritis should be ruled out.

Findings

A 47-year-old male from central India presented with swelling, pain, and redness in the left eye since 2 months. The patient was diagnosed elsewhere as having an extraocular extension of intraocular tumor and advised radiation brachytherapy for the same. Clinical examination revealed nodular scleritis in the left eye. The patient did not have any systemic illness or complaints suggestive of connective tissue disease. Laboratory investigations ruled out the same. However, Venereal Disease Research Laboratory (VDRL) test was positive. Rapid plasma reagin (RPR) test and Treponema pallidum hemagglutination assay (TPHA) were also positive, confirming the diagnosis of syphilis. Ultrabiomicroscopy (UBM) and ultrasound scan of the eye ruled out intraocular tumor. Treatment was initiated with benzathine penicillin 2.4 million units per week for 3 weeks to which the patient responded remarkably well.

Conclusions

Although rare, syphilis can present as nodular scleritis masquerading as ocular tumor. Syphilis must be considered in the list of etiological diagnoses in patients presenting with nodular scleritis, and testing for this disease should be a part of routine investigation in patients with scleritis.
No luck replicating the immune response in twins
Authors: Baxter Alan G , Hodgkin Philip D
Published: March 2015

Recent twin studies highlight the astonishing impact of non-heritable contributions to our immune health and wellbeing. Immunologists, long familiar with heterogeneity generated from within cells, must now grapple with heterogeneity between and within individuals which is present to an extraordinary degree. The capacity to interpret and find patterns in the face of such immune system diversity may be limited when sampling is restricted to blood, necessitating the development of new approaches.
RETRACTED ARTICLE: Matsaev type inequalities on smooth cones
Authors: Pang Sheng , Ychussie Beatriz
Published: March 2015

Our aim in this paper is to obtain Matsaev type inequalities about harmonic functions on smooth cones, which generalize the results obtained by Xu, Yang and Zhao in a half space.
The viscosity technique for the implicit midpoint rule of nonexpansive mappings in Hilbert spaces
Authors: Xu Hong-Kun , Alghamdi Maryam A , Shahzad Naseer
Published: March 2015

The viscosity technique for the implicit midpoint rule of nonexpansive mappings in Hilbert spaces is established. The strong convergence of this technique is proved under certain assumptions imposed on the sequence of parameters. Moreover, it is shown that the limit solves an additional variational inequality. Applications to variational inequalities, hierarchical minimization problems, and nonlinear evolution equations are included.
Finite element/percolation theory modelling of the micromechanical behavior of clayey soils
Authors: Pérez-Rea M Luz , Horta-Rangel Jaime , López-Lara Teresa , Hernández-Zaragoza Juan B , Alcocer Sergio M , Castaño Victor M
Published: March 2015

A hybrid model for soils, which combines percolation theory and finite element method is presented. The internal soil structure is modelled via the finite element method, and percolation networks are used for analyzing its mechanical behaviour. Through a microscopic characterization of elastic properties of soil grains, the model is generated. The effective percolation threshold obtained is lower than that of the network geometric percolation. The effective mechanical properties predicted are successfully compared to published experimental results.
Fixed drug eruption to sitagliptin
Authors: Gupta Mrinal , Gupta Anish
Published: March 2015

Fixed drug eruption is a common adverse effect seen with various drugs notably antibiotics, antiepileptics and non-steroidal anti-inflammatory drugs. Herein we report a case of Sitagliptin induced fixed drug eruption in a 46 year old female who developed circumscribed, erythematous macules all over the body within one week of initiation of Sitagliptin. The lesions resolved with residual hyperpigmentation on cessation of the drug. The diagnosis was confirmed by an oral provocation test which led to a reactivation of the lesions. To the best of our knowledge, this is the first case of fixed drug eruption to Sitagliptin reported in the literature.
Association of hyperglycemia in a general Japanese population with late-night-dinner eating alone, but not breakfast skipping alone
Authors: Nakajima Kei , Suwa Kaname
Published: March 2015

The unhealthy habit of late-night-dinner eating (LNDE) is often observed in adults. Since LNDE can lead to breakfast skipping (BS) the next morning, we examined the associations of LNDE and BS with hyperglycemia (HbA1c ≥ 5.7% and/or pharmacotherapy for diabetes), separately and in combination, in 61,364 apparently healthy Japanese adults aged 30–70 years. Although LNDE alone was significantly associated with hyperglycemia, even after adjustment for body mass index, BS alone was not. Our results indicate that hyperglycemia in the general Japanese population is associated with LNDE alone, but not BS alone.
Adaptation of Pseudomonas sp. AKS2 in biofilm on low-density polyethylene surface: an effective strategy for efficient survival and polymer degradation
Authors: Tribedi Prosun , Gupta Anirban Das , Sil Alok K
Published: March 2015

Background

Pseudomonas sp. AKS2 can efficiently degrade low-density polyethylene (LDPE). It has been shown that this degradation of LDPE by AKS2 is correlated to its ability to form biofilm on the polymer surface. However, the underlying mechanism of this biofilm-mediated degradation remains unclear. Since bioremediation potential of an organism is related to its adaptability in a given environment, we hypothesized that AKS2 cells undergo successful adaptation in biofilm on LDPE, which leads to higher level of LDPE degradation. To verify this, the current study investigated a number of parameters of AKS2 cells in biofilm that are known to be involved in adaptation process.

Results

Successful adaptation always develops a viable microbial population. So we examined the viability of AKS2 cells in biofilm. We observed the presence of viable population in the biofilm. To gain an insight, the growth of AKS2 cells in biofilm on LDPE at different time points was examined. Results showed a better reproductive competence and more colonization for AKS2 biofilm cells than planktonic cells, indicating the increased fitness of AKS2 biofilm cells than their planktonic counterpart. Towards understanding fitness, we determined the hydrolytic activity, different carbon source utilization potentials, functional diversity and homogeneity of AKS2 biofilm cells. Results showed increased hydrolytic activity (approximately 31%), higher metabolic potential, higher functional diversity (approximately 27%) and homogeneity for biofilm-harvested cells than planktonic cells. We also examined cellular surface hydrophobicity, which is important for cellular attachment to LDPE surface. Consistent with the above results, the cell surface hydrophobicity of biofilm-harvested AKS2 cells was found to be higher (approximately 26%) compared to that of their planktonic counterpart. All these results demonstrated the occurrence of physiological as well as structural adaptations of AKS2 cells in biofilm on LDPE surface that resulted in better attachment, better utilization of polymer and better growth of AKS2 cells, leading to the development of a stable colony on LDPE surface.

Conclusions

The present study shows that AKS2 cells in biofilm on LDPE surface undergo successful adaptation that leads to enhanced LDPE degradation, and thus, it helps us to understand the underlying mechanism of biofilm-mediated polymer degradation process by AKS2 cells.
Moisture management behaviour of modified polyester wool fabrics
Authors: Kumar Pawan , Sinha Sujit Kumar , Ghosh Subrata
Published: March 2015

To support the thermo regularity system of human body in completely changed environment and physical activity the functional clothing must create a stable microclimate next to the skin. The present study deals with the moisture transport and moisture management behaviour of polyester wool yarn and knitted fabric treated with two types of enzyme viz; alkaline protease enzyme and acidic protease enzyme. The prime object of this study was to enhance the moisture transport and moisture management properties of yarn and fabric for use in active wear. The results reveal superior wicking behaviour by alkaline protease enzyme treatment, while superior moisture vapour permeability with acidic protease enzyme treatment. Moisture management properties of alkaline protease enzyme treated fabric gives better result, ranging its grade from very good to excellent with higher absorption rate, one way transport capacity and spreading speed. Analysis of variance (ANOVA) was applied to test statistical significance level of all effects.
New dog and new tricks: evolving roles for IL-33 in type 2 immunity
Authors: Lott Jeremy M , Sumpter Tina L , Turnquist Hēth R
Published: March 2015

IL-33 is a more recently identified member of the IL-1 cytokine family, expressed in the nucleus of epithelial cells and released into the extracellular space following tissue damage. The impact of IL-33 as a regulator of the adaptive immune response has been studied extensively, with an understood role for IL-33 in the effector functions of CD4+ Th2 cells. IL-33, however, is now being shown to initiate the Th2-polarizing function of DCs, and stimulate the secretion of the type 2-associated cytokines, IL-4, IL-5, and IL-13, from tissue-resident innate-immune cells, especially ILCs and MCs. IL-33 also initiates and perpetuates local inflammatory responses through the recruitment and activation of type 2- and inflammatory-associated effectors, such as eosinophils, basophils, and neutrophils. As such, IL-33 drives and amplifies type 2-dependent immunity, as well as type 2-dependent tissue destruction and inflammation. It is also becoming apparent that IL-33 supports the reparative capacity of macrophage and ILCs, but these functions may also contribute to chronic fibrotic diseases. Herein, we review new developments in the understanding of IL-33 as it functions in Th2 cells and type 2 immunity. This includes a discussion of our evolving understanding of how IL-33 directly and indirectly promotes type 2 immune responses through action on innate cells in immunity and the pathogenesis of atopic and fibrotic diseases.
Circulating Tumor Cell Biomarker Panel As an Individual-Level Surrogate for Survival in Metastatic Castration-Resistant Prostate Cancer
Authors: Scher Howard I. , Heller Glenn , Molina Arturo , Attard Gerhardt , Danila Daniel C. , Jia Xiaoyu , Peng Weimin , Sandhu Shahneen K. , Olmos David , Riisnaes Ruth , McCormack Robert , Burzykowski Tomasz , Kheoh Thian , Fleisher Martin , Buyse Marc , de Bono Johann S.
Published: March 2015

Purpose

Trials in castration-resistant prostate cancer (CRPC) need new clinical end points that are valid surrogates for survival. We evaluated circulating tumor cell (CTC) enumeration as a surrogate outcome measure.

Patients and Methods

Examining CTCs alone and in combination with other biomarkers as a surrogate for overall survival was a secondary objective of COU-AA-301, a multinational, randomized, double-blind phase III trial of abiraterone acetate plus prednisone versus prednisone alone in patients with metastatic CRPC previously treated with docetaxel. The biomarkers were measured at baseline and 4, 8, and 12 weeks, with 12 weeks being the primary measure of interest. The Prentice criteria were applied to test candidate biomarkers as surrogates for overall survival at the individual-patient level.

Results

A biomarker panel using CTC count and lactate dehydrogenase (LDH) level was shown to satisfy the four Prentice criteria for individual-level surrogacy. Twelve-week surrogate biomarker data were available for 711 patients. The abiraterone acetate plus prednisone and prednisone-alone groups demonstrated a significant survival difference (P = .034); surrogate distribution at 12 weeks differed by treatment (P < .001); the discriminatory power of the surrogate to predict mortality was high (weighted c-index, 0.81); and adding the surrogate to the model eliminated the treatment effect on survival. Overall, 2-year survival of patients with CTCs < 5 (low risk) versus patients with CTCs ≥ 5 cells/7.5 mL of blood and LDH > 250 U/L (high risk) at 12 weeks was 46% and 2%, respectively.

Conclusion

A biomarker panel containing CTC number and LDH level was shown to be a surrogate for survival at the individual-patient level in this trial of abiraterone acetate plus prednisone versus prednisone alone for patients with metastatic CRPC. Additional trials are ongoing to validate the findings.
Human Epidermal Growth Factor Receptor 2 (HER2) –Specific Chimeric Antigen Receptor–Modified T Cells for the Immunotherapy of HER2-Positive Sarcoma
Authors: Ahmed Nabil , Brawley Vita S. , Hegde Meenakshi , Robertson Catherine , Ghazi Alexia , Gerken Claudia , Liu Enli , Dakhova Olga , Ashoori Aidin , Corder Amanda , Gray Tara , Wu Meng-Fen , Liu Hao , Hicks John , Rainusso Nino , Dotti Gianpietro , Mei Zhuyong , Grilley Bambi , Gee Adrian , Rooney Cliona M. , Brenner Malcolm K. , Heslop Helen E. , Wels Winfried S. , Wang Lisa L. , Anderson Peter , Gottschalk Stephen
Published: March 2015

Purpose

The outcome for patients with metastatic or recurrent sarcoma remains poor. Adoptive therapy with tumor-directed T cells is an attractive therapeutic option but has never been evaluated in sarcoma.

Patients and Methods

We conducted a phase I/II clinical study in which patients with recurrent/refractory human epidermal growth factor receptor 2 (HER2) –positive sarcoma received escalating doses (1 × 104/m2to 1 × 108/m2) of T cells expressing an HER2-specific chimeric antigen receptor with a CD28.ζ signaling domain (HER2-CAR T cells).

Results

We enrolled 19 patients with HER2-positive tumors (16 osteosarcomas, one Ewing sarcoma, one primitive neuroectodermal tumor, and one desmoplastic small round cell tumor). HER2-CAR T-cell infusions were well tolerated with no dose-limiting toxicity. At dose level 3 (1 × 105/m2) and above, we detected HER2-CAR T cells 3 hours after infusion by quantitative polymerase chain reaction in 14 of 16 patients. HER2-CAR T cells persisted for at least 6 weeks in seven of the nine evaluable patients who received greater than 1 × 106/m2HER2-CAR T cells (P = .005). HER2-CAR T cells were detected at tumor sites of two of two patients examined. Of 17 evaluable patients, four had stable disease for 12 weeks to 14 months. Three of these patients had their tumor removed, with one showing ≥ 90% necrosis. The median overall survival of all 19 infused patients was 10.3 months (range, 5.1 to 29.1 months).

Conclusion

This first evaluation of the safety and efficacy of HER2-CAR T cells in patients with cancer shows the cells can persist for 6 weeks without evident toxicities, setting the stage for studies that combine HER2-CAR T cells with other immunomodulatory approaches to enhance their expansion and persistence.
Survival, Durable Response, and Long-Term Safety in Patients With Previously Treated Advanced Renal Cell Carcinoma Receiving Nivolumab
Authors: McDermott David F. , Drake Charles G. , Sznol Mario , Choueiri Toni K. , Powderly John D. , Smith David C. , Brahmer Julie R. , Carvajal Richard D. , Hammers Hans J. , Puzanov Igor , Hodi F. Stephen , Kluger Harriet M. , Topalian Suzanne L. , Pardoll Drew M. , Wigginton Jon M. , Kollia Georgia D. , Gupta Ashok , McDonald Dan , Sankar Vindira , Sosman Jeffrey A. , Atkins Michael B.
Published: March 2015

Purpose

Blockade of the programmed death-1 inhibitory cell-surface molecule on immune cells using the fully human immunoglobulin G4 antibody nivolumab mediates tumor regression in a portion of patients with advanced treatment-refractory solid tumors. We report clinical activity, survival, and long-term safety in patients with advanced renal cell carcinoma (RCC) treated with nivolumab in a phase I study with expansion cohorts.

Patients and Methods

A total of 34 patients with previously treated advanced RCC, enrolled between 2008 and 2012, received intravenous nivolumab (1 or 10 mg/kg) in an outpatient setting once every two weeks for up to 96 weeks and were observed for survival and duration of response after treatment discontinuation.

Results

Ten patients (29%) achieved objective responses (according to RECIST [version 1.0]), with median response duration of 12.9 months; nine additional patients (27%) demonstrated stable disease lasting > 24 weeks. Three of five patients who stopped treatment while in response continued to respond for ≥ 45 weeks. Median overall survival in all patients (71% with two to five prior systemic therapies) was 22.4 months; 1-, 2-, and 3-year survival rates were 71%, 48%, and 44%, respectively. Grade 3 to 4 treatment-related adverse events occurred in 18% of patients; all were reversible.

Conclusion

Patients with advanced treatment-refractory RCC treated with nivolumab demonstrated durable responses that in some responders persisted after drug discontinuation. Overall survival is encouraging, and toxicities were generally manageable. Ongoing randomized clinical trials will further assess the impact of nivolumab on overall survival in patients with advanced RCC.