bluuebunny/crossref_metadata_2025 huggingface dataset:
The use of cannabinoids in chronic pain
Authors: Reynolds Timothy David , Osborn Hannah Louise
Published: July 2013

We present the case of a 56-year-old man who developed chronic pain following the excision of a facial cancer that was poorly controlled despite multiple analgesic medications. Following the starting of nabilone (a synthetic cannabinoid) his pain control was greatly improved and this had a huge impact on his quality of life. We also managed to significantly reduce his doses of opioid analgesia and ketamine. We review the current literature regarding the medicinal use of cannabinoids, with an emphasis on chronic pain, in an attempt to clarify their role and how to select patients who may benefit from this treatment.
Unconventional prosthodontics for the aesthetic rehabilitation of discoloured rotated maxillary central incisor
Authors: Singh Kunwarjeet , Kumar Narendra , Choudhary Nisha , Gupta Nidhi
Published: July 2013

Orthodontics is always the first choice treatment for aesthetic and functional rehabilitation of malaligned teeth but in some exceptionally rare cases, the unwillingness of the patient for orthodontic correction poses a tough challenge to the dentist. In such cases, the only other option for aesthetic restoration is the change in angulation with custom cast post and core followed by the placement of an aesthetic crown.
Sarcoidosis patient: an unexpected reaction to carbonic anhydrase enzyme inhibitor
Authors: Khedr Yahya A H , Khedr Abdulla H
Published: July 2013

Ocular diseases are very common in many of the systemic diseases such as sarcoidosis, and may sometimes be the presenting symptom of the disease. In this case report, we present an unusual reaction of the sarcoid granuloma to carbonic anhydrase enzyme inhibitors (CAIs), which was encountered in a patient with ocular sarcoidosis. This observation was taken after a 2-week interval between a CT scan orbits and an MRI orbits which showed a decrease in size from 4×3×4 cm to 2.5×2.5×2 cm, respectively. We suspected the dorzolamide CAI to have had a significant role in the reduction in size. It is suggested that acidotic changes that occur due to the effect of the carbonic anhydrase inhibitor causes electrolyte imbalance, intracellular as well as extracellular, which lead to the reduction in the size of the granuloma.
Olfactory dysfunction as first presenting symptom of cranial fibrous dysplasia
Authors: Tsakiropoulou Evangelia , Konstantinidis Iordanis , Chatziavramidis Angelos , Constantinidis Jannis
Published: July 2013

Fibrous dysplasia (FD) is a benign bone disorder presenting with a variety of clinical manifestations. This is the first reported case of anosmia as presenting symptom of FD. We present the case of a 72-year-old female patient with a progressive olfactory dysfunction. Clinical examination revealed evidence of chronic rhinosinusitis; therefore the patient was treated with a course of oral corticosteroids. The patient had no improvement in her olfactory ability and imaging studies were ordered. Bony lesions characteristic of craniofacial FD were found, causing obstruction of the central olfactory pathway. This case emphasises the need to conduct further investigations in patients with rhinosinusitis and olfactory dysfunction especially when they present no response to oral steroid treatment.
Chronic hepatitis C therapy: a rare complication revisited
Authors: Yaseen Alsabbagh Mohammed Eyad , Eisa Naseem , Alraiyes Abdul Hamid , Alraies M Chadi
Published: July 2013

The combined regimen of peg-interferon α2a plus ribavirin along with protease inhibitors (boceprevir or telaprevir) is considered as a very portent and effective therapy for hepatitis C infections. However, this combined therapy has been associated with a side effect that can make the course of the disease more complicated. In this case, a 50-year-old man developed insulin-dependent diabetes soon after initiating triple hepatitis C therapy. The treatment had to be stopped and the course of his hepatitis C infection has been challenged with this rare side effect.
Development and evaluation of the Supportive and Palliative Care Indicators Tool (SPICT): a mixed-methods study
Authors: Highet Gill , Crawford Debbie , Murray Scott A , Boyd Kirsty
Published: July 2013

Objective

To refine and evaluate a practical, clinical tool to help multidisciplinary teams in the UK and internationally, to identify patients at risk of deteriorating and dying in all care settings.

Methods

We used a participatory research approach to refine the 2010 Supportive and Palliative Care Indicators Tool (SPICT) and evaluate its use in clinical practice. We conducted an ongoing peer review process for 18 months via an open access webpage, and engaged over 30 clinicians from the UK and internationally in developing an effective tool. Secondly, we carried out a prospective case-finding study in an acute hospital in SE Scotland. Four multidisciplinary teams identified 130 patients with advanced kidney, liver, cardiac or lung disease following an unplanned hospital admission.

Results

The SPICT was refined and updated to consist of readily identifiable, general indicators relevant to patients with any advanced illness, and disease-specific indicators for common advanced conditions. Hospital clinicians used the SPICT to identify patients at risk of deteriorating and dying. Patients who died had significantly more unplanned admissions, persistent symptoms and increased care needs. By 12 months, 62 (48%) of the identified patients had died. 69% of them died in hospital, having spent 22% of their last 6 months there.

Conclusions

The SPICT can support clinical judgment by multidisciplinary teams when identifying patients at risk of deteriorating and dying. It helped identify patients with multiple unmet needs who would benefit from earlier, holistic needs assessment, a review of care goals, and anticipatory care planning.
FOCUSING TESTING BY USING INSPECTION AND PRODUCT METRICS
Authors: ELBERZHAGER FRANK , KREMER STEPHAN , MÜNCH JÜRGEN , ASSMANN DANILO
Published: July 2013

A well-known approach for identifying defect-prone parts of software in order to focus testing is to use different kinds of product metrics such as size or complexity. Although this approach has been evaluated in many contexts, the question remains if there are further opportunities to improve test focusing. One idea is to identify other types of information that may indicate the location of defect-prone software parts. Data from software inspections, in particular, appear to be promising. This kind of data might already lead to software parts that have inherent difficulties or programming challenges, and in consequence might be defect-prone. This article first explains how inspection and product metrics can be used to focus testing activities. Second, we compare selected product and inspection metrics commonly used to predict defect-prone parts (e.g. size and complexity metrics, inspection defect content metrics, and defect density metrics). Based on initial experience from two case studies performed in different environments, the suitability of different metrics for predicting defect-prone parts is illustrated. The studies revealed that inspection defect data seems to be a suitable predictor, and a combination of certain inspection and product metrics led to the best prioritizations in our contexts. In addition, qualitative experience is presented, which substantiates the expected benefit of using inspection results to optimize testing.
MAINTAINABILITY PREDICTORS FOR RELATIONAL DATABASE-DRIVEN SOFTWARE APPLICATIONS: EXTENDED RESULTS FROM A SURVEY
Authors: RIAZ MEHWISH , TEMPERO EWAN , SULAYMAN MUHAMMAD , MENDES EMILIA
Published: July 2013

Software maintainability is a very important quality attribute. Its prediction for relational database-driven software applications can help organizations improve the maintainability of these applications. The research presented herein adopts a survey-based approach where a survey was conducted with 40 software professionals aimed at identifying and ranking the important maintainability predictors for relational database-driven software applications. The survey results were analyzed using frequency analysis. The results suggest that maintainability prediction for relational database-driven applications is not the same as that of traditional software applications in terms of the importance of the predictors used for this purpose. The results also provide a baseline for creating maintainability prediction models for relational database-driven software applications.
RISK MANAGEMENT IN SOFTWARE PRODUCT LINE ENGINEERING: A MAPPING STUDY
Authors: LOBATO LUANNA LOPES , BITTAR THIAGO JABUR , NETO PAULO ANSELMO DA MOTA SILVEIRA , MACHADO IVAN DO CARMO , DE ALMEIDA EDUARDO SANTANA , MEIRA SILVIO ROMERO DE LEMOS
Published: July 2013

Software Product Line (SPL) Engineering focuses on systematic software reuse, which has benefits such as reductions in time-to-market and effort, and improvements in the quality of products. However, establishing a SPL is not a simple matter, and can affect all aspects of the organization, since the approach is complex and involves major investment and considerable risk. These risks can have a negative impact on the expected ROI for an organization, if SPL is not sufficiently managed. This paper presents a mapping study of Risk Management (RM) in SPL Engineering. We analyzed a set of thirty studies in the field. The results points out the need for risk management practices in SPL, due to the little research on RM practices in SPL and the importance of identifying insight on RM in SPL. Most studies simply mention the importance of RM, however the steps for managing risk are not clearly specified. Our findings suggest that greater attention should be given, through the use of industrial case studies and experiments, to improve SPL productivity and ensure its success. This research is a first attempt within the SPL community to identify, classify, and manage risks, and establish mitigation strategies.
SOFTWARE ARCHITECTURE RECOVERY THROUGH SIMILARITY-BASED GRAPH CLUSTERING
Authors: ZHU JIANLIN , HUANG JIN , ZHOU DAICUI , YIN ZHONGBAO , ZHANG GUOPING , HE QIANG
Published: July 2013

Software architecture recovery is to gain the architectural level understanding of a software system while its architecture description does not exist. In recent years, researchers have adopted various software clustering techniques to detect hierarchical structure of software systems. Most graph clustering techniques focus on the connectivity between program elements, but unreasonably ignore the similarity which is also a key measure for finding elements of one module. In this paper we propose a novel hierarchy graph clustering algorithm DGHC, which considers both similarity and connectivity between program elements. During the transformation of program dependence graph edges representing similarity between elements are added. Then similar elements are grouped by density-based approaches. The alternative strategy is adopted to find groups of closely connected and similar elements. Meanwhile we adjust the contribution of connectivity and similarity by a flexible clustering algorithm based on short random walk model, which can obtain more structure information of software to find its multiple layers. Furthermore a new method called Multi-layer Propagation Gap is proposed to suggest stable layers of hierarchy clustering result as multiple layers of software system. Extensive experimental results illustrate the effectiveness and efficiency of DGHC in detecting hierarchy structure of software through comparison with various software clustering methods.
Modelling effect of sericitization of plagioclase on the
40
K/
40
Ar and
40
Ar/
39
Ar chronometers: implication for dating basaltic rocks and mineral deposits
Authors: Verati Chrystèle , Jourdan Fred
Published: July 2013

The
40
Ar/
39
Ar technique is the most commonly used technique to date basaltic rocks. For basaltic rocks older than about 30 Ma, the dating of plagioclase separates is preferred over groundmass as the latter is susceptible to containing cryptic alteration due to fluid circulations, difficult if not impossible to remove during sample preparation. Alteration under such metamorphic conditions progressively forms K-rich sericite after plagioclase. Owing to its transparency, plagioclase allows a distinction to be made optically between partially–completely altered grains and fresh grains. However, practice shows that grains that contain less than about 1% of sericite are hard to identify under the stereomicroscope. Owing to the high K
2
O content (
c.
10 wt%) of sericite, such compromised grains can have dramatic effects on the age determination of plagioclase.

Here, we investigate and quantify the effect of sericite on the
40
Ar/
39
Ar age determination of plagioclase using a numerical model with multiple variable parameters. We show that the most influential parameter is the time difference between the crystallization of plagioclase and the sericitization event. We also show that for some continental flood basalts, even 0.1 wt% of sericite can bias the apparent age of a plagioclase separate by several hundred thousand years. The presence of sericite can be identified using a combination of Ca/K ratios, age spectra, and
39
Ar and
37
Ar degassing curves obtained during a conventional
40
Ar/
39
Ar step-heating procedure. When the age of the fresh plagioclase and its Ca/K ratio are known, the percentage of sericitization and the age of the alteration event can be estimated. Ultimately, above approximately 65% of sericitization, the apparent age measured on the altered plagioclase is within ±1% of the age of the alteration event, with implications for accurately dating low-temperature metamorphism and mineral deposit formations.

Supplementary material:

Further details of calculation are available at
www.geolsoc.org.uk/SUP18609
.
40
Ar/
39
Ar geochronology and the diffusion of
39
Ar in phengite–muscovite intergrowths during step-heating experiments
in vacuo
Authors: Forster Marnie A. , Lister Gordon S.
Published: July 2013

Step-heating experiments
in vacuo
are routine when conducting
40
Ar/
39
Ar geochronology, including for white mica. White mica can break down, due to dehydroxylation and delamination, so experiments involving mica are often conducted in relative haste, and not with the care and precision necessary when intending to apply multi-diffusion-domain theory to model the results. Here we show, however, that carefully managed step-heating experiments appear to allow release of argon through solid-state diffusion processes alone. We analysed phengite-muscovite intergrowths in high-pressure metamorphic rocks exhumed in and beneath extensional ductile shear zones during continental extension. Such materials often yield Arrhenius plots in which there is a distinct steepening of slope mid-way through the step-heating sequence. This steepening appears to correspond with steps in which release of argon from phengite components dominate. We analysed the data using a computer program (
eArgon
) and numerically simulated mixing of gas released from multiple diffusion domains. The results suggest that diffusion of
39
Ar in phengitic white mica involves radically different diffusion parameters in comparison with muscovite. If these results extrapolate to nature then
40
Ar/
39
Ar geochronology may allow direct dating of white mica mineral growth during metamorphism.

Supplementary material:

Data files A, B and C are available at
www.geolsoc.org.uk/SUP18619
. Data file A C++ computer code used to infer data for an Arrhenius plot, assuming different diffusion geometries. These methods are excerpted from the
eArgon
computer program used to analyse these data.

Data file B Analytical methods and procedures used in the laboratory for
40
Ar/
39
Ar geochronology performed on the samples reported.

Data file C XML formatted data tables for the step-heating experiments reported in this study, in a form that can be read by the
eArgon
computer program.
Untrained young men have dysfunctional HDL compared with strength-trained men irrespective of body weight status
Authors: Roberts Christian K. , Katiraie Michael , Croymans Daniel M. , Yang Otto O. , Kelesidis Theodoros
Published: July 2013

We examined the impact of strength fitness and body weight on the redox properties of high-density lipoprotein (HDL) and associations with indices of vascular and metabolic health. Ninety young men were categorized into three groups: 1) overweight untrained (OU; n = 30; BMI 30.7 ± 2.1 kg/m2); 2) overweight trained [OT; n = 30; BMI 29.0 ± 1.9; ≥4 d/wk resistance training (RT)]; and 3) lean trained (LT; n = 30; BMI 23.7 ± 1.4; ≥4 d/wk RT). Using a novel assay on the basis of the HDL-mediated rate of oxidation of dihydrorhodamine (DOR), we determined the functional (redox) properties of HDL and examined correlations between DOR and indices of vascular and metabolic health in the cohort. DOR was significantly lower in both trained groups compared with the untrained group (LT, 1.04 ± 0.49; OT, 1.39 ± 0.57; OU, 1.80 ± 0.74; LT vs. OU P < 0.00001; OT vs. OU P = 0.02), however, DOR in the OT group was not significantly different from that of the LT group. DOR was negatively associated with HDL-cholesterol ( R = −0.64), relative strength ( R = −0.42), sex hormone-binding globulin ( R = −0.42), and testosterone ( R = −0.35) (all P ≤ 0.001); whereas DOR was positively associated with triglycerides ( R = 0.39, P = 0.002), oxidized low-density lipoprotein ( R = 0.32), body mass index ( R = 0.43), total mass ( R = 0.35), total fat mass ( R = 0.42), waist circumference ( R = 0.45), and trunk fat mass ( R = 0.42) (all P ≤ 0.001). Chronic RT is associated with improved HDL redox activity. This may contribute to the beneficial effects of RT on reducing cardiovascular disease risk, irrespective of body weight status.
Adult Stature and Risk of Cancer at Different Anatomic Sites in a Cohort of Postmenopausal Women
Authors: Kabat Geoffrey C. , Anderson Matthew L. , Heo Moonseong , Hosgood H. Dean , Kamensky Victor , Bea Jennifer W. , Hou Lifang , Lane Dorothy S. , Wactawski-Wende Jean , Manson JoAnn E. , Rohan Thomas E.
Published: July 2013

Background: Prospective studies in Western and Asian populations suggest that height is a risk factor for various cancers. However, few studies have explored potential confounding or effect modification of the association by other factors.

Methods: We examined the association between height measured at enrollment in 144,701 women participating in the Women's Health Initiative and risk of all cancers combined and cancer at 19 specific sites. Over a median follow-up of 12.0 years, 20,928 incident cancers were identified. We used Cox proportional hazards models to estimate HR and 95% confidence intervals (CI) per 10 cm increase in height, with adjustment for established risk factors. We also examined potential effect modification of the association with all cancer and specific cancers.

Results: Height was significantly positively associated with risk of all cancers (HR = 1.13; 95% CI, 1.11–1.16), as well as with cancers of the thyroid, rectum, kidney, endometrium, colorectum, colon, ovary, and breast, and with multiple myeloma and melanoma (range of HRs: 1.13 for breast cancer to 1.29 for multiple myeloma and thyroid cancer). These associations were generally insensitive to adjustment for confounders, and there was little evidence of effect modification.

Conclusions: This study confirms the positive association of height with risk of all cancers and a substantial number of cancer sites.

Impact: Identification of single-nucleotide polymorphisms associated both with height and with increased cancer risk may help elucidate the association. Cancer Epidemiol Biomarkers Prev; 22(8); 1353–63. ©2013 AACR.
Concurrent Radiotherapy and Ipilimumab Immunotherapy for Patients with Melanoma
Authors: Barker Christopher A. , Postow Michael A. , Khan Shaheer A. , Beal Kathryn , Parhar Preeti K. , Yamada Yoshiya , Lee Nancy Y. , Wolchok Jedd D.
Published: July 2013

Ipilimumab and radiotherapy are commonly used to treat unresectable and metastatic melanoma. Results from preclinical studies and case reports suggest a biologic interaction between these two treatments. To understand the clinical implications of the interaction, we carried out a retrospective study reviewing records of patients treated with ipilimumab and radiotherapy for melanoma at our institution between 2005 and 2011. The review included details of treatment, response, adverse events (AE), and overall survival (OS). Twenty-nine patients underwent 33 courses of non-brain radiotherapy between their first and last dose of ipilimumab. Immune-related AEs (ir-AEs) were observed in 43% of patients receiving ipilimumab at 10 mg/kg and in 22% of patients receiving 3 mg/kg; the frequency of ir-AEs was not significantly different compared with previous studies of ipilimumab alone. Radiotherapy-related AEs were significantly more common in patients receiving higher doses of radiation. Palliation of symptoms was reported by 77% of patients after radiotherapy. Median OS was 9 and 39 months in patients receiving radiotherapy during induction and maintenance with ipilimumab, respectively. In this retrospective study, concurrent ipilimumab and radiotherapy was neither associated with higher than expected rates of AEs nor did it abrogate palliative effects of radiotherapy or survival benefits of ipilimumab. Further studies to prospectively explore the efficacy of this therapeutic combination are warranted. Cancer Immunol Res; 1(2); 92–98. ©2013 AACR.
Effect of Conversion from ESA with Shorter Half-Life to CERA Once Monthly for Maintaining Hb Concentration in Pre-Dialysis CKD Patients
Authors: Choi Ji-Young , Yang Chul Woo , Kim Yeong-Hoon , Joo Kwon Wook , Yoo Tae-Hyun , Lee Kang Wook , Lee Sang-Ho , Moon Ju-Young , Shin Sug Kyun , Huh Wooseong , Kim Nam-Ho , Park Sun-Hee , Kim Chan-Duck , Kim Yong-Lim
Published: July 2013

Background: The purpose of this study is to identify whether hemoglobin (Hb) concentrations can be maintained, and to investigate changes in biomarkers, when switching from erythropoietin stimulating agents (ESA) with shorter half-life to once-monthly subcutaneous methoxy polyethylene glycol-epoetin β (CERA) in pre-dialysis chronic kidney disease (CKD) patients. Methods: Pre-dialysis CKD patients (n=191) aged ≥18 years who maintained their Hb level 10-12 g/dL through use of epoetin-α, epoetin-β, or darbepoetin-α were enrolled. Hb levels and CERA dose was assessed prospectively for 24 weeks. Serum biomarkers related to coagulation, endothelial function, and iron metabolism were measured at weeks 0 and 24. Results: Baseline Hb concentration was 10.8±0.6 g/dL Twelve and 24 weeks after conversion, mean Hb levels were 11.9±0.9 and 11.2±0.9 g/dL, respectively. The mean monthly CERA dose required to maintain Hb levels was gradually reduced. Of total 387 dose adjustments, dose increases and decreases occurred in 35 (9.0%) and 352 (91.0%) episodes, respectively. Hb overshoot occurred in 14 (9.7%) patients. P-selectin was significantly decreased, whereas VCAM was significantly increased 24 weeks after conversion (P < 0.05). Serum soluble transferrin receptor E-selectin and prohepcidin levels were similar before and after switching to CERA (P=N-S). Conclusion: Conversion from ESA with shorter half-life to subcutaneous once-monthly CERA in pre-dialysis CKD patients can efficaciously maintain Hb. The CERA dose requirement decreased significantly. The conversion ratio may need to be reduced when switching from ESA with shorter half-life to CERA. CERA may change biomarkers associated with platelet reactivity and endothelial microenvironment.
Use of Placebo Interventions in Primary Care in Poland
Authors: Bąbel Przemysław
Published: July 2013

Objective: The aim of the study was to investigate the behavior, beliefs and attitudes of Polish primary care physicians concerning the use of placebo interventions. Subjects and Methods: A total of 220 Polish primary care physicians (internists, specialists in family medicine and pediatricians) were asked to participate in a questionnaire survey and 171 agreed to do so. The questionnaire was a self-report of the behavior, beliefs and attitudes of physicians concerning the use of placebo interventions in clinical practice. The percentages are based on the actual number of respondents to each question. Results: Of 169 respondents, 135 (80%) declared that they used or prescribed placebo interventions, with 20/169 (12%) doing so almost every day, 51/169 (30%) once a week and 44/169 (26%) once a month. The most common placebos used were vitamins (86/135, 66%) and homeopathy (73/135, 56%). Among the participants, 114/129 (84%) reported that the placebos were effective, with only 10/129 (8%) considering them rarely effective; 75/139 (54%) of the physicians considered placebo interventions to be effective only in patients with subjective symptoms, 116/139 (73%) indicated that individual traits of patients were decisive factors in the effectiveness of placebo interventions, and 103/159 (65%) thought that the expectations of patients were of importance. A total of 128/170 (75%) respondents thought that the mechanism of placebo effects was purely psychological. Conclusion: The use and prescription of placebo interventions seemed to be very common among Polish primary care physicians studied and they generally had positive attitudes towards their use and effectiveness.
Validation of the Arabic Version of the Early Inflammatory Arthritis Detection Tool
Authors: Al-Jarallah K. , Shehab D. , Moussa M.A.A. , Abraham M.
Published: July 2013

Objective: To evaluate the reliability and validity of the Arabic version of the Early Inflammatory Arthritis Questionnaire (EIAQ-A), a detection tool for screening for early inflammatory arthritis (EIA) in Arabic-speaking populations. Subjects and Methods: A cross-sectional study was conducted among 30 consecutive participants (21 female and 9 male) attending the Internal Medicine Outpatient Clinic at Mubarak Al-Kabeer Hospital. They completed the self-administered EIAQ-A twice within a 2-week period. Their disease activity was evaluated during the visits based on clinical and laboratory variables. Cross-cultural adaptation was performed using forward and backward translations of the original questionnaire. Test-retest reliability of the EIAQ-A was evaluated using the measure of agreement, kappa (κ), between the response of participants in the two interviews. Internal consistency of the EIAQ-A was measured using the Kudar-Richardson-20 coefficient (KR-20), a binary response equivalent to Cronbach's a. External construct validity was assessed by Spearman's rank correlation coefficient (rs) between the score of EIAQ-A and both clinical and laboratory variables of disease activity. Results: The test-retest reliability for EIAQ-A was good (κ = 0.558) for the overall score and between 0.841 and 0.368 for the subscale scores. Internal consistency had an acceptable value of KR-20 = 0.869. The construct validity for EIAQ-A was high for all disease activity variables tested, rs was between 0.727 (swollen joint count) and 0.896 (visual analog scale pain score). Conclusion: The EIAQ-A was a reliable and valid tool for population screening for EIA. Its use may accelerate the early detection of EIA in Arabic-speaking communities.
Increased Total Renin Levels but Not Angiotensin-Converting Enzyme Activity in Obese Patients with Polycystic Ovary Syndrome
Authors: Alphan Ziynet , Berberoglu Zehra , Gorar Suheyla , Candan Zehra , Aktas Aynur , Aral Yalcin , Ademoglu Esranur
Published: July 2013

Objective: To investigate the renin-angiotensin-aldosterone system and angiotensin-converting enzyme (ACE) activity in patients with polycystic ovarian syndrome (PCOS). Subjects and Methods: In this case-control study, 41 obese (PCOS) women and 29 healthy controls, matched for age and body mass index, were enrolled. Anthropometric, metabolic, and hormonal patterns, including plasma aldosterone, plasma renin, and ACE activity, were measured in each subject. Results: Plasma renin levels were significantly higher in PCOS patients (19.7 ± 14.5 µg/ml) compared with controls (12.9 ± 9.0 µg/ml, p < 0.05). ACE activity and aldosterone levels did not significantly differ between both groups (p = 0.15 and p = 0.18, respectively). Analysis of PCOS patients showed a significant correlation of fasting insulin levels with levels of renin (r = 0.305, p < 0.01) and free testosterone (r = 0.384, p = 0.001). Similarly, homeostasis model assessment index was positively correlated with total renin concentrations (r = 0.366, p < 0.01) and free testosterone (r = 0.352, p < 0.01). Conclusion: Obese PCOS women had higher total renin levels, but not ACE activity and aldosterone levels, related to insulin resistance compared with controls.
Attitudes and Behaviour regarding Deep Dentin Caries Removal: A Survey among German Dentists
Authors: Schwendicke F. , Meyer-Lueckel H. , Dörfer C. , Paris S.
Published: July 2013

Incomplete removal of deep caries has been shown to reduce the risks of pulp exposure and postoperative pulpal complications. It is therefore of interest whether dentists perform one- or two-step incomplete excavation, and which criteria and methods they use to assess and provide removal of deep caries. This study investigated the attitudes and behaviour of dentists in northern Germany using a new, validated questionnaire. The survey included 2,346 practitioners, 821 (35%) of whom responded. Demographic and sensitivity analysis did not indicate selection bias. 50% of dentists considered only complete excavation, even if pulp exposure was likely. If caries was to be removed incompletely, 77% considered two-step excavation. Hardness was the most important criterion to assess excavation. To treat an exposed pulp, 75% of dentists considered direct capping, 70% refused incomplete excavation fearing caries progression or pulp damage, and 59% reported to prefer more invasive treatment to facilitate restoration longevity. Over 50% recognised an influence of professional regulations on their treatment decisions. There was a moderate correlation between attitudes and behaviour of dentists, with dentists who suspected residual caries to be harmful rejecting incomplete excavation and vice versa. Cluster analysis identified two groups of dentists with opposite attitudes and behaviour, independently from dentist's age or gender. In conclusion, the majority of surveyed dentists was sceptical about leaving caries during excavation and does not practice incomplete caries removal. Therefore, benefits of partial excavation should be highlighted in under- and postgraduate education and regulatory incentives modified to promote minimally invasive techniques.
Hyperdense Posterior Cerebral Artery Sign in a Setting of Spontaneous Vertebral Artery Dissection: A Blessing in Disguise?
Authors: Gokhale Sankalp , Graffagnino Carmelo
Published: July 2013

Objective: To report a case of a hyperdense posterior cerebral artery (PCA) sign in the setting of spontaneous vertebral artery dissection. Clinical Presentation and Intervention: A 28-year-old, previously healthy female presented with rapidly progressive coma. A noncontrast computerized tomographic (CT) scan showed a hyperdense PCA sign, which prompted an urgent arteriogram. She was found to have spontaneous vertebral artery dissection with an occluding thrombus. She underwent intra-arterial thrombolysis with tissue plasminogen activator. Follow-up magnetic resonance imaging showed an area of acute infarction in the medial temporal and occipital regions corresponding to the area supplied by the left PCA. The patient was started on systemic anticoagulation therapy with intravenous heparin. She showed slow and continued recovery but was left with significant neurological deficits that required posthospital discharge to a long-term rehabilitation facility. Conclusion: This case showed that the hyperdense PCA sign on a noncontrast CT scan necessitated an emergent CT angiogram that showed vertebral artery dissection and a devastating vascular occlusion. Hence, we suggest an early intervention that may allow for potential revascularization therapy.
Turning Theory into Practice: The Development of Modern Transdermal Drug Delivery Systems and Future Trends
Authors: Perumal O. , Murthy S.N. , Kalia Y.N.
Published: July 2013

Despite its remarkable barrier function, the skin remains an attractive site for systemic drug delivery given its easy accessibility, large surface area and the possibility to bypass the gastrointestinal tract and the liver and so modify drug absorption kinetics. The pioneering work of Scheuplein, Higuchi and others in the 1960s helped to explain the processes involved in passive percutaneous absorption and led to the development of mathematical models to describe transdermal drug delivery. The intervening years have seen these theories turned to practice and a significant number of transdermal systems are now available including some that employ active drug delivery. This review briefly discusses the evolution of transdermal therapeutic systems over the years and the potential of newer transdermal technologies to deliver hydrophilic drugs and macromolecules through the skin.
Heart Rate Recovery Is Impaired in Patients with Psoriasis
Authors: Sarli Bahadir , Dogan Yasemin , Baktir Ahmet Oguz , Saglam Hayrettin , Arinc Huseyin , Kurtul Serkan , Avci Atıl , Cinar Levent , Akpek Mahmut , Kaya Mehmet G.
Published: July 2013

Objective: The aim of this study was to investigate the relationship between psoriasis and heart rate recovery (HRR) index. Patients and Methods: A total of 50 patients with a diagnosis of psoriasis and 32 healthy volunteers were included in the study. In all patients, a stress test was performed to calculate the HRR index in a manner which aimed to reach the age-specific maximum heart rate. HRR indices were calculated in all patients and controls. Results: HRR (beats/minute) indices after the 1st (HRR1, 26 ± 10 vs. 33 ± 8, p = 0.002), 2nd (44 ± 11 vs. 50 ± 6, p = 0.002), 3rd (51 ± 7 vs. 63 ± 8, p < 0.001), 4th (54 ± 7 vs. 65 ± 8, p < 0.001) and 5th (57 ± 8 vs. 70 ± 10, p < 0.001) minutes of the recovery period were significantly lower in the psoriasis group compared to healthy controls. In addition, HRR1 was significantly correlated with duration of psoriasis (r = 0.541, p < 0.001) and psoriasis area and severity index score (r = 0.511, p < 0.001). Conclusion: HRR was lower in patients with psoriasis. Given the prognostic value of this test, patients with psoriasis might be at risk for future cardiovascular events and cardiovascular mortality.
Passive and Iontophoretic Transport through the Skin Polar Pathway
Authors: Li S.K. , Peck K.D.
Published: July 2013

The purpose of the present article is to briefly recount the contributions of Prof. William I. Higuchi to the area of skin transport. These contributions include developing fundamental knowledge of the barrier properties of the stratum corneum, mechanisms of skin transport, concentration gradient across skin in topical drug applications that target the viable epidermal layer, and permeation enhancement by chemical and electrical means. The complex and changeable nature of the skin barrier makes it difficult to assess and characterize the critical parameters that influence skin permeation. The systematic and mechanistic approaches taken by Dr. Higuchi in studying these parameters provided fundamental knowledge in this area and had a measured and lasting influence upon this field of study. This article specifically reviews the validation and characterization of the polar permeation pathway, the mechanistic model of skin transport, the influence of the dermis on the target skin concentration concept, and iontophoretic transport across the polar pathway of skin including the effects of electroosmosis and electropermeabilization.
Richard Guy and His Collaborators: ‘Crackling' the Skin Code
Authors: Delgado-Charro M.B.
Published: July 2013

This paper aims to summarize the contributions of Richard Guy and collaborators to the skin field. Major contributions have been areas such as the modelling of skin absorption, use of spectroscopic techniques (Fourier transform infrared spectroscopy, attenuated total reflectance Fourier transform infrared spectroscopy and impedance spectroscopy) to characterize the skin barrier and the effects of enhancing techniques on the membrane, dermatopharmacokinetics and assessment of topical bio-availability, iontophoresis and reverse iontophoresis, and use of imaging techniques to elucidate pathways of penetration and the skin disposition of nanoparticles. The field of topical and transdermal drug delivery has benefitted incalculably from the extensive work of Guy and his group: their findings about mechanisms of drug delivery and permeation enhancement, and the development of methodologies which are now accepted as gold standards by skin scientists.
Engineering Approaches to Transdermal Drug Delivery: A Tribute to Contributions of Prof. Robert Langer
Authors: Mitragotri S.
Published: July 2013

Transdermal drug delivery continues to provide an advantageous route of drug administration over injections. While the number of drugs delivered by passive transdermal patches has increased over the years, no macromolecule is currently delivered by the transdermal route. Substantial research efforts have been dedicated by a large number of researchers representing varied disciplines including biology, chemistry, pharmaceutics and engineering to understand, model and overcome the skin's barrier properties. This article focuses on engineering contributions to the field of transdermal drug delivery. The article pays tribute to Prof. Robert Langer, who pioneered the engineering approach towards transdermal drug delivery. Over a period spanning nearly 25 years since his first publication in the field of transdermal drug delivery, Bob Langer has deeply impacted the field by quantitative analysis and innovative engineering. At the same time, he has inspired several generations of engineers by collaborations and mentorship. His scientific insights, innovative technologies, translational efforts and dedicated mentorship have transformed the field.
Current Understanding of Skin Biology Pertinent to Skin Penetration: Skin Biochemistry
Authors: Wertz P.W.
Published: July 2013

The purpose of this review is to summarize some of the biochemical or chemical findings that have contributed most significantly to our current understanding of the permeability barrier of the skin. This literature survey covers the period from the 1970s up to the present. This seems appropriate since earlier progress was comprehensively covered in a 1978 review by Bob Scheuplein entitled ‘Permeability of the skin: a review of major concepts' and in the earlier review by Scheuplein and Blank entitled ‘Permeability of the skin'. Both of these review articles are still being cited, and the earlier one has been cited more than 800 times. Overlap with material covered in these earlier publications will be minimized. The overall significance of findings from some of the most recent years may not yet be determined. The emphasis will be placed on the determination of the composition and structures of the epidermal lipids, especially those of the stratum corneum, key enzymes in the biosynthesis of these lipids and some of the physical chemical properties of these lipids as revealed by X-ray diffraction, infrared spectroscopy and other physical methods.
Cytogenetic Nomenclature: Changes in the ISCN 2013 Compared to the 2009 Edition
Authors: Simons A. , Shaffer L.G. , Hastings R.J.
Published: July 2013

The latest edition of the International System for Human Cytogenetic Nomenclature, ISCN 2013, has recently been published following a thorough revision of the 2009 issue and the incorporation of suggestions from the community by the current standing committee. This review will highlight the multiple nomenclature changes in the respective chapters of the 2013 version compared to the previous version of the ISCN published in 2009. These highlights are meant as a guide for the cytogeneticist to assist in the transition in the use of this updated nomenclature for describing cytogenetic and molecular cytogenetic findings in both clinical and research reports.
Attenuation of Ischemia/Reperfusion-Induced Ovarian Damage in Rats: Does Edaravone Offer Protection?
Authors: Ergenoglu Mete , Erbaş Oytun , Akdemir Ali , Yeniel Ahmet Özgür , Yildirim Nuri , Oltulu Fatih , Aktuğ Hüseyin , Taskiran Dilek
Published: July 2013

Aim: The aim of this study was to investigate whether prophylactic treatment with edaravone prevents ischemia/reperfusion (I/R)-induced ovarian damage during pneumoperitoneum in an experimental rat model. Methods: Twenty-eight female Sprague Dawley rats were allocated randomly to 4 groups. The sham group (group 1) was only subjected to catheter insertion, not to pneumoperitoneum. Group 2 received a 1 mg/kg dose of 0.9% sodium chloride by the intraperitoneal route for 10 min before pneumoperitoneum. Groups 3 and 4 received 6 and 12 mg/kg edaravone, respectively, by the intraperitoneal route for 10 min before pneumoperitoneum. After 60 min of pneumoperitoneum, the gas was deflated. Immediately after the reperfusion period, both ovaries were excised for histological scoring, caspase-3 immunohistochemistry and biochemical evaluation including glutathione (GSH) and malondialdehyde (MDA) levels. Also, total antioxidant capacity (TAC) was measured in plasma samples to evaluate the antioxidant effect of edaravone. Results: Ovarian sections in the saline group revealed higher scores for follicular degeneration and edema (p < 0.0001) when compared with the sham group. Administration of different doses of edaravone in rats significantly prevented degenerative changes in the ovary (p < 0.0001). Caspase-3 expression was only detected in the ovarian surface epithelium in all groups, and there was a significant difference between the treatment groups and the saline group (p < 0.0001). Treatment of rats with edaravone reduced caspase-3 expression in a dose-dependent manner. Moreover, biochemical measurements of oxidative stress markers (MDA, GSH and TAC) revealed that prophylactic edaravone treatment attenuated oxidative stress induced by I/R injury. Conclusion: These results indicate that prophylactic treatment with edaravone prevents I/R-induced ovarian damage during pneumoperitoneum in an experimental rat model.
Annette Bunge: Developing the Principles in Percutaneous Absorption Using Chemical Engineering Principles
Authors: Stinchcomb A.L.
Published: July 2013

Annette Bunge and her research group have had the central theme of mathematically modeling the dermal absorption process. Most of the research focus has been on estimating dermal absorption for the purpose of risk assessment, for exposure scenarios in the environment and in the occupational setting. Her work is the basis for the United States Environmental Protection Agency's estimations for dermal absorption from contaminated water. It is also the basis of the dermal absorption estimates used in determining if chemicals should be assigned a ‘skin notation' for potential systemic toxicity following occupational skin exposure. The work is truly translational in that it started with mathematical theory, is validated with preclinical and human experiments, and then is used in guidelines to protect human health. Her valued research has also extended into the topical drug bioavailability and bioequivalence assessment field.
Intravitreal Injection of Dexamethasone Implant in Serous Macular Detachment Associated with Waldenström's Disease
Authors: Fenicia Vito , Balestrieri Marco , Perdicchi Andrea , Maraone Giorgia , Recupero Santi Maria
Published: July 2013

Purpose: To evaluate the efficacy of one intravitreal injection of dexamethasone (Ozurdex®; Allergan, Inc., Irvine, Calif., USA) in serous macular detachment (SMD) of one eye, associated with bilateral central retinal vein occlusion (CRVO) in a patient affected by Waldenström's macroglobulinemia (WM). Patients and Methods: A female patient, affected by WM, complained of a progressive decrease in visual acuity, mainly in the left eye (LE). SMD in the LE associated with bilateral CRVO was diagnosed. One intravitreal injection of dexamethasone was administered in the LE and the patient was tested 1, 2, and 6 months after the injection. Results: 1, 2, and 6 months after the injection, the spectral domain optical coherence tomography (SD-OCT) showed a progressive slight reduction of foveal thickness that was not related to any improvement of visual function. Conclusions: Treatment with dexamethasone (Ozurdex) induced a progressive slight reduction of SMD but no improvement of visual acuity, and it is possible that this is related to the condition of hematic hyperviscosity that is present in WM.
Serum Fibroblast Growth Factor-21 Levels Are Associated With Carotid Atherosclerosis Independent of Established Cardiovascular Risk Factors
Authors: Chow Wing Sun , Xu Aimin , Woo Yu Cho , Tso Annette W.K. , Cheung Stephen C.W. , Fong Carol H.Y. , Tse Hung Fat , Chau Ming Tak , Cheung Bernard M.Y. , Lam Karen S.L.
Published: July 2013

Objective—

Serum levels of fibroblast growth factor-21 (FGF21), a metabolic hormone, have been shown to be elevated in subjects with adverse lipid profiles, obesity, metabolic syndrome, impaired glucose tolerance, type 2 diabetes mellitus, and hypertension. Recently, elevated serum FGF21 levels have also been reported in subjects with coronary heart disease or carotid artery plaques. However, whether serum FGF21 is independently associated with atherosclerotic diseases remains unclear. In this study, we examined the relationship between serum FGF21 levels and carotid intima-media thickness (IMT) in a large cohort of Southern Chinese subjects.

Approach and Results—

The cohort consisted of 670 subjects who underwent carotid IMT measurement. Serum FGF21 levels were measured with an ELISA kit. Serum FGF21 levels positively correlated with carotid IMT in women (
r
=0.32;
P
<0.001), but not in men (
r
=0.06;
P
=0.305). On multiple linear regression analysis, elevated serum FGF21 level in women was an independent risk factor for increased carotid IMT (
P
=0.039), together with age (
P
<0.001) and hypertension (
P
=0.011), in a model comprising also waist circumference, smoking history, serum creatinine, high sensitive C-reactive protein, dysglycemia, and dyslipidemia (adjusted
R
2
=35.8%;
P
<0.001). Elevated serum FGF21 levels were also a significant independent risk factor of carotid IMT on multiple stepwise regression analysis (
P
=0.01).

Conclusions—

The present study is the first demonstration that elevated serum FGF21 levels are associated with carotid atherosclerosis in humans, independent of established risk factors including adverse lipid profiles and C-reactive protein. The role of FGF21 as a biomarker or therapeutic target of atherosclerotic diseases warrants further investigation.