bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Macular Choroidal Thickness on Visual Function in Highly Myopic Eyes
Authors: Parravano Mariacristina , Oddone Francesco , Giorno Paola , Cacciamani Andrea , Abbate Rosa , Caminiti Giulia , Peiretti Enrico , Varano Monica
Published: September 2014

Purpose: To explore the retinal and choroidal thicknesses (RT, CT), as measured using enhanced depth imaging (EDI) optical coherence tomography (OCT, Spectralis) in highly myopic eyes and its relationship with visual function. Materials and Methods: Prospective, case-control, noninterventional clinical study. CT was measured by EDI-OCT in highly myopic eyes (≥6 dpt) without any macular diseases and age-matched control eyes. A complete ophthalmological examination, visual acuity assessment and MP1 microperimetry were obtained. Results: 38 myopic (15 M/23 F, mean age 51 ± 8.9 years) and 21 control eyes (5 M/16 F, mean age 50 ± 5.4 years) were included. The myopic mean refractive error was -13.3 ± 4.9 dpt and axial length 29.2 ± 2.2 mm. The mean best-corrected visual acuity (BCVA) was lower in highly myopic than in control eyes (77.3 ± 9.25 vs. 84.8 ± 0.6 letters, p = 0.0001, respectively) as was the mean retinal sensitivity (MRS; 16.32 ± 2.6 vs. 19.9 ± 0.2 dB, p < 0.0001). While RT was similar between groups (291.5 ± 24.2 vs. 283.6 ± 13.9 µm, p = 0.06, respectively), subfoveal CT was thinner in highly myopic compared to control eyes (114.3 ± 78.5 vs. 272.6 ± 110.2 µm, p < 0.0001). A significant relationship was found between subfoveal CT and MRS (R2 = 0.22; p = 0.003) and BCVA (R2 = 0.13; p = 0.027). Conclusions: Macular function is reduced in highly myopic eyes without any visible macular diseases compared to controls, and a significant proportion of the macular function variability seems to be related to a reduced CT.
Effects of Pumpkin Seed in Men with Lower Urinary Tract Symptoms due to Benign Prostatic Hyperplasia in the One-Year, Randomized, Placebo-Controlled GRANU Study
Authors: Vahlensieck Winfried , Theurer Christoph , Pfitzer Edith , Patz Brigitte , Banik Norbert , Engelmann Udo
Published: September 2014

Introduction: The German Research Activities on Natural Urologicals (GRANU) study was a randomized, partially blinded, placebo-controlled, parallel-group trial that investigated the efficacy of pumpkin seed in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (BPH/LUTS). Subjects and Methods: A total of 1,431 men (50−80 years) with BPH/LUTS were randomly assigned to either pumpkin seed (5 g b.i.d.), capsules with pumpkin seed extract (500 mg b.i.d.) or matching placebo. The primary response criterion was a decrease in International Prostate Symptom Score (IPSS) of ≥5 points from baseline after 12 months. Secondary outcome measures included IPSS-related quality of life, IPSS single items and diary-recorded nocturia. Results: After 12 months, the response rate (intention-to-treat/last-observation-carried-forward approach) did not differ between pumpkin seed extract and placebo. In the case of pumpkin seed (responders: 58.5%), the difference compared with placebo (responders: 47.3%) was descriptively significant. The study products were well tolerated. Overall, in men with BPH, 12 months of treatment with pumpkin seed led to a clinically relevant reduction in IPSS compared with placebo. Conclusion: In order to fully justify a recommendation for the use of pumpkin seed to treat moderate LUTS, these findings need to be substantiated in a confirmatory study or systematic review.
Growth Hormone Dose-Dependent Pubertal Growth: A Randomized Trial in Short Children with Low Growth Hormone Secretion
Authors: Albertsson-Wikland Kerstin , Kriström Berit , Lundberg Elena , Aronson A. Stefan , Gustafsson Jan , Hagenäs Lars , Ivarsson Sten-A. , Jonsson Björn , Ritzén Martin , Tuvemo Torsten , Westgren Ulf , Westphal Otto , Åman Jan
Published: September 2014

Background/Aims: Growth hormone (GH) treatment regimens do not account for the pubertal increase in endogenous GH secretion. This study assessed whether increasing the GH dose and/or frequency of administration improves pubertal height gain and adult height (AH) in children with low GH secretion during stimulation tests, i.e. idiopathic isolated GH deficiency. Methods: A multicenter, randomized, clinical trial (No. 88-177) followed 111 children (96 boys) at study start from onset of puberty to AH who had received GH 33 µg/kg/day for ≥1 year. They were randomized to receive 67 µg/kg/day (GH67) given as one (GH67×1; n = 35) or two daily injections (GH33×2; n = 36), or to remain on a single 33 µg/kg/day dose (GH33×1; n = 40). Growth was assessed as heightSDSgain for prepubertal, pubertal and total periods, as well as AHSDS versus the population and the midparental height. Results: Pubertal heightSDSgain was greater for patients receiving a high dose (GH67, 0.73) than a low dose (GH33×1, 0.41, p < 0.05). AHSDS was greater on GH67 (GH67×1, -0.84; GH33×2, -0.83) than GH33 (-1.25, p < 0.05), and heightSDSgain was greater on GH67 than GH33 (2.04 and 1.56, respectively; p < 0.01). All groups reached their target heightSDS. Conclusion: Pubertal heightSDSgain and AHSDS were dose dependent, with greater growth being observed for the GH67 than the GH33 randomization group; however, there were no differences between the once- and twice-daily GH67 regimens.
Comorbidity between Post-Traumatic Stress Disorder and Borderline Personality Disorder: A Review
Authors: Frías Álvaro , Palma Carol
Published: September 2014

Background: Traditionally, the presence of post-traumatic stress disorder (PTSD) in subjects diagnosed with borderline personality disorder (BPD) has been the object of scant empirical research. The clarification of issues related to the different areas of study for this comorbidity is not only significant from a theoretical point of view but also relevant for clinical practice. The aim of this review is to describe the main theoretical findings and research conclusions about the comorbidity between PTSD and BPD. Methods: A literature review was carried out via PubMed and PsycINFO for the period between 1990 and September 2013. The descriptors used were ‘post-traumatic stress disorder', ‘borderline personality disorder', ‘PTSD', ‘complex PTSD' and ‘BPD'. Results: Epidemiological studies show that the risk of PTSD among BPD subjects is not regularly higher than in subjects with other personality disorders. Furthermore, there is no conclusive evidence about the main aetiopathogenic mechanism of this comorbidity, either of one disorder being a risk factor for the other one or of common underlying variables. Concerning comparative studies, several studies with PTSD-BPD subjects have found a higher severity of psychopathology and psychosocial impairment than in BPD subjects. With regard to nosological status, the main focus of controversy is the validation of ‘complex PTSD', a clinical entity which may comprise a subgroup of PTSD-BPD subjects. With regard to treatment, there are preliminary evidences for the efficient treatment of psychopathology in both PTSD and BPD. Conclusions: These findings are remarkable for furthering the understanding of the link between PTSD and BPD and their implications for treatment. The results of this review are discussed, including methodological constraints that hinder external validity and consistency of referred findings.
Long-Term Utility and Durability of the Therapeutic Effects of Bimatoprost 0.03% for Eyelash Augmentation in Healthy Asian Subjects
Authors: Kwon Ohsang , Kim Jin Yong , Paik Seung Hwan , Jeon Hye Chan , Jung Ye-Jin , Lee Yoonhee , Baek Ji Hye , Chun Ji Hoon , Lee Won-Soo , Lee Jun Young , Rogers John D. , Halstead Michael , Eun Hee Chul
Published: September 2014

Background: Eyelashes of Asians differ from those of Caucasians in morphology and growth characteristics. Ethnic differences also exist for the tolerability profile of prostaglandin analogues. Objective: To evaluate the long-term utility and durability of bimatoprost 0.03% in eyelash augmentation in Asian females. Methods: One cohort received bimatoprost 0.03% for 36 weeks and another for 20 weeks, with the latter cohort followed for 16 weeks after treatment cessation. The primary endpoint was the percent change in eyelash length at week 20. Secondary measures included percent change in eyelash thickness and darkness, physician's Global Eyelash Assessment and patient satisfaction. Results: At week 20, eyelash length was enhanced in a time-dependent manner, with maximum improvement achieved (19.3%; p < 0.0001). Significant improvements in thickness and darkness were also achieved (22.9%, 6.0%; p < 0.0001). 77.8% of subjects improved by ≥1 grade on Global Eyelash Assessment, with 83.1% satisfied/very satisfied. Improvements were maintained with ongoing treatment to 36 weeks, while these effects were progressively lost with discontinuation. Conclusion: Bimatoprost 0.03% safely enhanced eyelashes in Asian females, maintained with ongoing treatment. Cessation of treatment was associated with progressive loss of effects.
Switch from Intravitreal Ranibizumab to Bevacizumab for the Treatment of Neovascular Age-Related Macular Degeneration: Clinical Comparison
Authors: Pinheiro-Costa João , Freitas-da-Costa Paulo , Falcão Manuel S. , Brandão Elisete M. , Falcão-Reis Fernando , Carneiro Ângela M.
Published: September 2014

Objective: To compare outcomes after switching from intravitreal ranibizumab to bevacizumab in neovascular age-related macular degeneration (AMD). Methods: A retrospective review of 110 eyes treated in a 1+PRN (pro re nata) clinical setting with ranibizumab that were switched to bevacizumab. Patients analyzed had at least 3 ranibizumab injections followed by at least 3 bevacizumab injections. Changes in best-corrected visual acuity (BCVA), retinal thickness and frequency of injections were compared. Results: The mean duration of ranibizumab treatment was 18.1 months, followed by 12.2 months of bevacizumab. Mean injection rates per month were similar (0.54 and 0.56 respectively, p = 0.230). There were no significant differences between BCVA at baseline and at the time of the switch (52.4 and 54.8 letters, p = 0.059). After the switch, there was a statistically significant decrease in BCVA to 51.7 letters (p < 0.001). Conclusion: Switching patients to bevacizumab may have a minor negative effect on the initial gain obtained with ranibizumab; however the degenerative history of wet AMD could explain this small variation in visual acuity.
Laparoscopic Management of Renal Tumors with Macroscopic Level 1 Renal Vein Involvement
Authors: Castillo Octavio , Silva Andrés , Alemán Enrique
Published: September 2014

Objective: To describe our surgical experience and clinical outcome in laparoscopic radical nephrectomy (LRN) for renal cell carcinoma (RCC) with level 1 renal vein tumor thrombus. Patients and Methods: 11 patients with RCC level 1 renal vein tumor thrombus were treated by LRN plus thrombectomy. The mean age was 66.8 years (SD ±11.313); the mean body mass index was 24.76 (SD ±5.091). In all cases, the surgical technique was defined by tumor characteristics and the surgeon's preferences. Results: Surgery was technically successful in all 11 patients. A hand-assisted approach was performed in 3 patients, while pure laparoscopy was used in 8. The mean surgical time was 108.3 min (SD ±28.284); the mean estimated blood loss was 108.33 ml (SD ±106.066); the average hospital stay was 2.8 days (SD ±0.707). There was 1 intraoperative complication (splenic laceration) that was managed laparoscopically. Pathologic examination confirmed RCC in all cases. There were no positive surgical margins. With a mean follow-up of 29 months (27-39), 2 patients had a recurrence. Conclusion: This report provides further evidence of the technical feasibility, safety and oncologic adequacy of the laparoscopic approach in RCC with level 1 renal vein involvement. A longer follow-up and multi-institutional studies are needed to adequately evaluate its potential oncologic benefit.
Diffusion Tensor Imaging, Intracranial Vascular Resistance and Cognition in Middle-Aged Asymptomatic Subjects
Authors: López-Olóriz Jorge , López-Cancio Elena , Arenillas Juan F. , Hernández María , Dorado Laura , Dacosta-Aguayo Rosalía , Barrios Maite , Soriano-Raya Juan José , Miralbell Júlia , Bargalló Núria , Cáceres Cynthia , Torán Pere , Alzamora Maite , Dávalos Antonio , Mataró Maria
Published: September 2014

Background: The contribution of traditional vascular risk factors to cognitive impairment and dementia is well known. However, in order to obtain possible targets for prevention of vascular cognitive impairment (VCI), it may be important to identify other early and noninvasive markers in asymptomatic middle-aged adults. The calculation of middle cerebral artery-pulsatility index (MCA-PI) is an ultrasonologic, noninvasive, validated and easily reproducible technique to assess increased distal resistance to blood flow. This study aims to assess the relationship between MCA-PI, microstructural white matter (WM) integrity and cognition in a middle-aged asymptomatic population. Methods: Ninety-five participants from the Barcelona-Asymptomatic Intracranial Atherosclerosis (AsIA) neuropsychology study were included. Subjects were 50-65 years old, free from dementia and without history of vascular disease. Transcranial color-coded duplex ultrasound examination was performed to assess MCA-PI as a measure of vascular resistance. WM integrity was evaluated by fractional anisotropy (FA) measurements of diffusion tensor images (DTI) acquired on a 3T-MRI. The neuropsychological battery was specifically selected to be sensitive to VCI, and included tests that were grouped into six cognitive domains: executive functioning, attention, verbal fluency, memory, visuospatial skills and psychomotor speed. A multivariate linear regression model adjusted for age, gender, years of education, diabetes and hypertension was performed. Results: MCA-PI was significantly associated with WM disintegration in different tracts (fornix, corticospinal and anterior thalamic), all p < 0.05 uncorrected. Both mean MCA-PI and mean FA of those significant tracts were independently associated with poor performance in attention, psychomotor speed, and visuospatial skills after adjustment for age, gender, years of education, and vascular risk factors (all p < 0.05). MCA-PI was independently associated with lower scores in all cognitive domains, except for visuospatial skills. Conclusions: Our data suggest that MCA-PI may be related to WM disintegration and early vascular cognitive impairment in middle-aged subjects. Although further prospective studies are needed to provide evidence for its validity in longitudinal studies, our results support the proposal of including MCA-PI as part of clinical assessment in order to identify targets for VCI prevention.
The Importance of Continuity in Inhaler Device Choice for Asthma and Chronic Obstructive Pulmonary Disease
Authors: Bjermer Leif
Published: September 2014

Inhaled therapies are central to the treatment of asthma and chronic obstructive pulmonary disease. Physicians consider many factors when selecting the most appropriate inhaler device, including device efficacy and the cost to the health care system. This review aims to discuss the factors that are important when considering inhaler devices and the importance of continuity in the choice of inhaler device. A large number of factors can contribute to therapeutic outcomes with inhalation devices. The inhalation technique is critical to treatment success and differs substantially between inhaler devices. Misuse of an inhaler is common, and thorough training of patients and physicians is important to ensure correct utilization. Patient satisfaction is an important consideration because it is significantly correlated with compliance and better outcomes. Financial pressures contribute to decision making: although selecting the less expensive inhaler device might reduce direct treatment costs, it can have a large impact on disease control and the patient's well-being. Switching may be associated with a poor inhalation technique, reduced disease control and quality of life, increased use of other treatments and health care resources, and a greater chance of unsuccessful treatment. Nonconsensual switches can result in patient discontent, reduced confidence in the medication, and uncertainty regarding the degree of disease control. It is recommended that patients with stable disease remain on their current device. If a switch is considered, the patient should be consulted and the physician should take into account the patient's preference, their ability to correctly use the device, and the availability of the preferred drug in the preferred device.
Comparison of Three Tracheal Intubation Techniques in Thyroid Tumor Patients with a Difficult Airway: A Randomized Controlled Trial
Authors: Liu Ling , Yue Hui , Li Jincheng
Published: September 2014

Objective: To investigate the effectiveness of the Shikani optical stylet (SOS) and GlideScope video laryngoscope (GVL) for tracheal intubation of thyroid tumor patients with a difficult airway. Subjects and Methods: One hundred and twenty thyroid tumor patients with a difficult airway, who were undergoing elective surgery requiring general anesthesia, were enrolled in the study. They were randomly allocated to 3 groups (n = 40 each) who underwent direct laryngoscopy (DL), SOS or GVL. The outcomes recorded were time to intubation, first-attempt success rate, mean artery pressure (MAP), heart rate (HR) and incidence of complications. Results: The mean time to intubation in the SOS group (group S; 42.4 ± 24.1 s) and the GLV group (group G; 29.8 ± 22.3 s) was significantly less than that in the DL group (group D) (68.8 ± 26.6 s). The first-attempt success rate in group S (90.0%) and group G (97.5%) was significantly higher than that in group D (75.0%; all p < 0.05). The HR and MAP at 1 min after intubation were lowest in group S (76.4 ± 9.2 beats/min and 12.9 ± 1.1 kPa), followed by group G (79.9 ± 9.3 beats/min and 13.0 ± 0.9 kPa) and then group D (90.4 ± 8.1 beats/min and 16.6 ± 1.2 kPa). The difference was statistically significant (all p < 0.05). The incidence of lip or mucosal trauma was lowest in group S, followed by group G and then group D. Conclusion: The SOS and the GLV had advantages over the DL in the management of thyroid tumor patients with a difficult airway in terms of a shorter time to intubation, a higher first-attempt success rate and a reduced incidence of complications. Thus, a rational choice of one of these techniques may be better for the perioperative safety of thyroid tumor patients with a difficult airway.
Alterations of Canalicular ATP-Binding Cassette Transporter Expression in Drug-Induced Liver Injury
Authors: Zollner Gernot , Thueringer Andrea , Lackner Carolin , Fickert Peter , Trauner Michael
Published: September 2014

Background: Drug-induced liver injury (DILI) is a major clinical problem and its pathogenesis is poorly understood. The association of DILI with polymorphisms in hepatobiliary transport systems suggests a role for transport proteins in the pathogenesis of DILI. Aim: To investigate expression and tissue distribution of hepatobiliary transport systems in DILI. Methods: Expression of the canalicular bile salt export pump BSEP (ABCC11), phospholipid flippase MDR3 (ABCB4) and bilirubin export pump MRP2 (ABCC2) was assessed immunohistochemically in liver biopsies from 23 patients with DILI. Results: Of 12 patients with cholestatic DILI (mostly due to antibiotics), 8 displayed a marked reduction of MRP2, MDR3 and BSEP expression. Transporter staining was normal in 4 patients with cholestatic DILI. In 11 patients with necroinflammatory hepatocellular injury (most frequently caused by NSAIDs), transporter staining was normal in areas where hepatocyte morphology was preserved. Due to hepatocyte necrosis and the reduction of the hepatocyte number, overall transporter expression was reduced without a reduction in transporter expression at the single hepatocyte level. Conclusions: Canalicular ABC transporter expression is profoundly disturbed in most cases of cholestatic DILI. Drug-induced hepatitis does not lead to repression of transporter expression but to hepatocyte drop-outs with a numerical loss of bile canaliculi.
Analysis of Correlations between Patient-Oriented SCORAD (PO-SCORAD) and Other Assessment Scores of Atopic Dermatitis Severity and Quality of Life
Authors: Coutanceau Christine , Stalder Jean-François
Published: September 2014

Objective: Self-assessment scores such as the Patient-Oriented Scoring of Atopic Dermatitis (PO-SCORAD) index being recommended by public health authorities for chronic disease management, we aimed at analysing correlations between PO-SCORAD and physician and patient assessment scores of atopic dermatitis (AD) severity and quality of life. Methods: We perfomed an observational study conducted in 12 European countries in 4,222 atopic patients aged ≥1 month and prescribed Exomega® emollient cream. AD severity was measured by the SCORAD index, PO-SCORAD, Patient-Oriented Eczema Measure (POEM) and Self-Administered Eczema Area and Severity Index (SA-EASI) scales, and patient and family quality of life by the Dermatology Life Quality Index (DLQI) and Dermatitis Family Questionnaire Impact (DFQI) scales, respectively. Their correlations were analysed. Results: PO-SCORAD was the only self-assessment score to be highly correlated with the SCORAD index and POEM (r ≥ 0.70). It was also the best correlated with the DLQI (r = 0.67) and DFQI (r = 0.56). After a 5-week treatment, SCORAD index and PO-SCORAD severity scores had decreased significantly by 60 and 56% (p < 0.0001), and quality of life had improved. Conclusion: PO-SCORAD is better correlated with quality of life scales than other self-assessment scores.
Correlation of Ultrasound Estimated with Dye-Determined or Directly Measured Amniotic Fluid Volume Revisited
Authors: Magann Everett F. , Ounpraseuth Songthip , Chauhan Suneet P. , Ranganathan Anaanth S. , Dajani Nafisa K. , Bergstrom Jennifer , Morrison John C.
Published: September 2014

Background/Aims: To examine the relationship of the amniotic fluid index (AFI) and single deepest pocket (SDP) with an AFV as modelled by Brace or Magann. Methods: AFI and SDP were evaluated for their correlation with an actual AFV using the Spearman correlation coefficient. Results: 482 AFI and 468 SDP pregnancies were evaluated. There was a significant association between the AFI and SDP and an actual AFV (p < 0.0001). The AFI range of 5.1-20 was better correlated than 5.1-24 for normal AFVs Brace (κ = 0.175) and Magann (κ = 0.356) versus 5.1-24 (κ = 0.150 and κ = 0.319), respectively. The agreement level t for the AFI (κ = 0.175) and SDP (κ = 0.126) using Brace was slight and for the AFI (κ = 0.356) and SDP (κ = 0.295) using Magann was fair. Conclusions: Both the AFI and SDP were correlated with actual AFV using both models. AFI of 5.1-20 better categorizes normal volumes. Although the Magann model correlates AFI/SDP and AFV better, the superiority is minimal.
Effects of Daily Consumption of Synbiotic Bread on Insulin Metabolism and Serum High-Sensitivity C-Reactive Protein among Diabetic Patients: A Double-Blind, Randomized, Controlled Clinical Trial
Authors: Tajadadi-Ebrahimi Maryam , Bahmani Fereashteh , Shakeri Hossein , Hadaegh Haleh , Hijijafari Mohammad , Abedi Fatemeh , Asemi Zatollah
Published: September 2014

Background: This study was conducted to evaluate the effects of daily consumption of synbiotic bread on the metabolic status of patients with type 2 diabetes mellitus. Methods: This randomized, double-blind, controlled clinical trial was performed in 81 diabetic patients. The subjects were randomly assigned to consumption of synbiotic (n = 27), probiotic (n = 27), or control bread (n = 27) for 8 weeks 3 times a day in a 40-gram package. The synbiotic bread contained Lactobacillus sporogenes (1 × 108 CFU) and 0.07 g inulin per 1 g. The probiotic bread contained L. sporogenes (1 × 108 CFU per 1 g). Fasting blood samples were taken at baseline and after an 8-week intervention for quantification of related factors. Results: Consumption of the synbiotic bread resulted in a significant reduction in serum insulin levels (-3.2 ± 5.4 vs. -0.3 ± 3.4 and 0.6 ± 4.7 µIU/ml, respectively, p = 0.007), homeostatic model assessment for insulin resistance scores (-1.5 ± 2.7 vs. -0.2 ± 1.6 and 0.4 ± 3.5, respectively, p = 0.03), and homeostatic model assessment-β-cell function (-7.2 ± 16.3 vs. -0.7 ± 10.8 and 0.7 ± 8.2, respectively, p = 0.04) compared to the probiotic and control breads. We did not find any significant effect of synbiotic bread consumption on fasting plasma glucose, the quantitative insulin sensitivity check index, or serum hs-CRP levels compared to other breads. Conclusion: Consumption of the synbiotic bread among diabetic patients had beneficial effects on insulin metabolism.
Genomic Characteristics and Changes of Avian Infectious Bronchitis Virus Strain CK/CH/LDL/97I after Serial Passages in Chicken Embryos
Authors: Zhao Fei , Han Zongxi , Zhang Tingting , Shao Yuhao , Kong Xiangang , Ma Huijie , Liu Shengwang
Published: September 2014

Background: We previously attenuated the infectious bronchitis virus (IBV) strain CK/CH/LDL/97I and found that it can convey protection against the homologous pathogenic virus. Objective: To compare the full-length genome sequences of the Chinese IBV strain CK/CH/LDL/97I and its embryo-passaged, attenuated level to identify sequence substitutions responsible for the attenuation and define markers of attenuation. Methods: The full-length genomes of CK/CH/LDL/97I P5 and P115 were amplified and sequenced. The sequences were assembled and compared using the MEGALIGN program (DNAStar) and a phylogenetic tree was constructed using MEGA4 software. Results: The CK/CH/LDL/97I virus population contained subpopulations with a mixture of genetic mutants. Changes were observed in nsp4, nsp9, nsp11/12, nsp14, nsp15, nsp16, and ORF3a, but these did not result in amino acid substitutions or did not show functional variations. Amino acid substitutions occurred in the remaining genes between P5 and P115; most were found in the S region, and some of the nucleotide mutations resulted in amino acid substitutions. Among the 9 nsps in the ORF1 region, nsp3 contained the most nucleotide substitutions. Conclusions: Sequence variations in different genes, especially the S gene and nsp3, in the genomes of CK/CH/LDL/97I viruses might contribute to differences in viral replication, pathogenicity, antigenicity, immunogenicity, and tissue tropism.
Aberrant Soluble Epoxide Hydrolase and Oxylipin Levels in a Porcine Arteriovenous Graft Stenosis Model
Authors: Terry Christi M. , Carlson Mary L. , He Yuxia , Ulu Arzu , Morisseau Christophe , Blumenthal Donald K. , Hammock Bruce D. , Cheung Alfred K.
Published: September 2014

Synthetic arteriovenous grafts (AVGs) used for hemodialysis frequently fail due to the development of neointimal hyperplasia (NH) at the vein-graft anastomosis. Inflammation and smooth-muscle cell (SMC) and myofibroblast proliferation and migration likely play an important role in the pathogenesis of NH. Epoxyeicosatrienoic acids (EETs), the products of the catabolism of arachidonic acid by cytochrome P450 enzymes, possess anti-inflammatory, antiproliferative, antimigratory and vasodilatory properties that should reduce NH. The degradation of vasculoprotective EETs is catalyzed by the enzyme, soluble epoxide hydrolase (sEH). sEH upregulation may thus contribute to NH development by the enhanced removal of vasculoprotective EETs. In this study, sEH, cytochrome P450 and EETs were examined after AVG placement in a porcine model to explore their potential roles in AVG stenosis. Increased sEH protein expression, decreased P450 epoxygenase activity and dysregulation of 5 oxylipin mediators were observed in the graft-venous anastomotic tissues when compared to control veins. Pharmacological inhibitors of sEH decreased the growth factor-induced migration of SMCs and fibroblasts, although they had no significant effect on the proliferation of these cells. These results provide insights on epoxide biology in vascular disorders and a rationale for the development of novel pharmacotherapeutic strategies to prevent AVG failure due to NH and stenosis.
Effects of High-Frequency Bio-Oxidative Ozone Therapy in Temporomandibular Disorder-Related Pain
Authors: Doğan Mansur , Özdemir Doğan Derya , Düger Cevdet , Özdemir Kol İclal , Akpınar Aysun , Mutaf Burcu , Akar Türker
Published: September 2014

Objective: It was the aim of this study to compare the efficacy of ozone therapy and drug treatment in patients with painful temporomandibular joint (TMJ) disorder (TMD). Subjects and Methods: A total of 63 patients with TMD were enrolled; 33 were treated with bio-oxidative therapy and 30 with a ketoprofen tablet thiocolchicoside capsule 2 × 1 for 7 days. Maximum voluntary interincisal mouth opening (MMO) was measured in millimeters using a scale and recorded during the pre- and posttreatment periods. The patients evaluated their subjective pain using a visual analogue scale (VAS). Data were analyzed using the Mann-Whitney U test, the Kolmogorov-Smirnov test, and the independent t test. Results: The mean MMO of the group that received ozone therapy during the pretreatment period was 46.51 ± 8.2 mm, and it immediately increased to 48.78 ± 7.5 mm after 1 week of ozone therapy, which was statistically significant (p = 0.04). For those who received medication, the mean MMO during the pretreatment period was 46.30 mm, and at the end of 1 week it was 46.9 mm. In the ozone group, 29% of patients showed a gradual decrease in their VAS pain scores compared to pretreatment values (6.3 ± 2.1 to 3.0 ± 2.2). In the medication group, 24% of patients showed a significant decrease in VAS pain scores during the follow-up period (6.9 ± 1.4 to 5.0 ± 1.5). Conclusion: This study showed that bio-oxidative therapy was a more effective treatment than medication therapy for relieving TMJ pain.
Regression of Solid Tumors by Induction of MazF, a Bacterial mRNA Endoribonuclease
Authors: Shimazu Tsutomu , Mirochnitchenko Oleg , Phadtare Sangita , Inouye Masayori
Published: September 2014

MazF from Escherichia coli is an endoribonuclease that specifically cleaves mRNAs at ACA sequences. Its induction in mammalian cells has been shown to cause programmed cell death. Here we explored if a bacterial MazF-MazE toxin-antitoxin system can be used for gene therapy. For this, we first constructed a tetracycline-inducible MazF expression system in human embryonic kidney cells (T-Rex 293-mazF). Solid tumors were formed by injecting T-Rex 293-mazF cells into nude mice. All 8 mice injected with the cells developed solid tumors, which regressed upon induction of MazF. In 4 mice, tumors completely regressed, while in the remaining 4 mice, tumors reappeared after apparent significant regression, which was found to be due to the lack of presence of functional MazF. Notably, the MazF-mediated regression of the tumors was counteracted by the expression of its cognate antitoxin MazE. These results indicate that a bacterial MazF-MazE toxin-antitoxin system may have potential to be used as a therapeutic tool.
Increased Prevalence of Testicular Adrenal Rest Tumours during Adolescence in Congenital Adrenal Hyperplasia
Authors: Claahsen-van der Grinten Hedi L. , Dehzad Farhang , Kamphuis-van Ulzen Karin , de Korte Chris L.
Published: September 2014

Testicular adrenal rest tumours (TART) are one of the most important causes of infertility in adult male patients with congenital adrenal hyperplasia (CAH). These benign tumours are already detected in children, but screening of TART is not routinely performed. Objective: To define retrospectively the prevalence of TART in 41 paediatric male CAH patients aged 0-19 years regularly followed by high-frequency (Fcentral 12-MHz) ultrasound techniques. Results: Above the age of 10 years, there was a clear increase in the prevalence of TART: 10-12 years, 28% (2 of 7 patients), 13-14 years, 50% (4/8), and 15-16 years, 75% (3/4). Above the age of 16 years, TART were detected in 100% of the patients (7/7). The tumours were not detectable by palpation. Conclusion: TART is already present in childhood with an increasing prevalence after onset of puberty. We recommend regular ultrasound from the onset of puberty in all boys with classic CAH.
In vitro and in vivo Activity of the Dimer of PMAP-36 Expressed in Pichia pastoris
Authors: Wang Liang , Zhang Hao , Jia Zhiqiang , Ma Qingquan , Dong Na , Shan Anshan
Published: September 2014

The antimicrobial peptide PMAP-36 exists as a homodimer stabilized by an intermolecular disulfide bridge. The dimer of PMAP-36 exhibits a potent and rapid microbicidal activity against a wide spectrum of microorganisms. The gene encoding the antiparallel dimer (PMAP-36)2 was designed and codon-optimized according to bias of Pichia pastoris. The gene was then expressed in the P. pastoris strain GS115. The concentration of the recombinant product reached 106 mg/l. In vitro activity assays indicated that the recombinant peptide showed antimicrobial activities against Gram-positive and Gram-negative bacteria but did not cause hemolysis of chicken erythrocytes. Subsequently, 120 7-day-old male Arbor Acres broilers were used to evaluate the in vivo activities of the peptide. A prophylactic dose of ciprofloxacin lactate was supplemented as the control. The results showed that recombinant (PMAP-36)2 significantly increased the serum IgM content of the birds (p < 0.05). The recombinant peptide significantly increased the amounts of Bifidobacterium and decreased the amount of Escherichia coli cells in the ceca of the experimental birds (p < 0.05). The results obtained in the present study indicate that the recombinant (PMAP-36)2 has a potent in vitro and in vivo activity and can be used as an alternative to antibiotic treatment.
Resistant Palmoplantar Lesions in Patients of Psoriasis: Evaluation of the Causes and Comparison of the Frequency of Delayed-Type Hypersensitivity in Patients without Palm and Sole Lesions
Authors: Al-Mutairi Nawaf , Abdalla Tarek O. , Nour Tarek M.
Published: September 2014

Objective: To examine the reasons for resistance to treatment in cases of palmoplantar psoriasis, and also to compare the frequency of delayed-type hypersensitivity to common sensitizers with those cases of psoriasis without palmoplantar involvement. Subjects and Methods: One hundred and three patients with resistant palmoplantar psoriasis were examined for a possible drug reaction, fungal infection or contact allergy. Patch testing was done for another 100 patients with psoriasis vulgaris without palm and sole involvement. χ2, Fischer's exact test, Mann-Whitney U test and logistical regression analysis were done using SPSS 15.0. Results: Of the 103 patients with resistant palmoplantar lesions, 26 (25.24%) had a positive patch test to at least one of the tested allergens, 6 (5.8%) had psoriasiform spongiotic dermatitis on biopsy, 5 (4.8%) reported exacerbation after starting biologic therapy and 3 (2.9%) were potassium hydroxide positive in the sole lesions. In comparison, of the 100 patients with no palm or sole lesions, 11 (11%) had a positive patch test to at least one of the allergens. There was a direct relationship between the increase in the prevalence of dermatitis and the duration of psoriasis. There was no correlation between the clinical type of psoriasis and patch-test positivity. Conclusion: Secondary fungal infection, allergic contact dermatitis to topical agents or common allergens, or at times an unusual reaction to the antipsoriatic therapeutic agents sometimes led to treatment failure in patients with psoriasis vulgaris with palmoplantar lesions. Also, psoriasis patients with palm and sole lesions tended to have higher rates of contact hypersensitivity than patients without lesions on their palms and soles.
Screening of Alternative Drugs to the Tumor Suppressor miR-375 in Esophageal Squamous Cell Carcinoma Using the Connectivity Map
Authors: Isozaki Yuka , Hoshino Isamu , Akutsu Yasunori , Hanari Naoyuki , Mori Mikito , Nishimori Takanori , Murakami Kentaro , Akanuma Naoki , Toyozumi Takeshi , Takahashi Masahiko , Suito Hiroshi , Takeshita Nobuyoshi , Maruyama Tetsuro , Suzuki Akane , Nakayama Toshinori , Matsubara Hisahiro
Published: September 2014

Objective: The aim of this study was to identify alternative compounds to the tumor suppressor miR-375 using the connectivity map (CMAP) and to validate the antitumor effects of the identified drugs in esophageal squamous cell carcinoma (ESCC). Methods: Gene profiling of miR-375-treated TE2 and T.Tn cells was applied in order to search the CMAP database. Among the compounds identified using the CMAP, we focused on 8 drugs [(-)-epigallocatechin-3-gallate, metformin, rosiglitazone among others], excluding 2 drugs among the top 10 compounds. We evaluated whether these compounds possess tumor-suppressive functions in ESCC. Results: A cytotoxicity assay showed that the sensitivity of TE2 and T.Tn cells treated with the 8 compounds was evaluated based on IC50 values of 42.9 µM to 3.8 mM. A cell cycle analysis revealed that the percentage of TE2 and T.Tn cells incubated with 6 compounds in the G0/G1 phase or the G2/M phase increased by approximately 40-80%. A TUNEL assay showed that the percentages of apoptotic cells treated with almost all compounds were significantly increased (p < 0.05) compared with the control cells. Conclusion: The CMAP database is a useful tool for identifying compounds affecting the same molecular pathways, particularly products that are difficult to apply via practical approaches, such as microRNAs.
Rethinking the Role of Immunoglobulin E and Its High-Affinity Receptor: New Insights into Allergy and Beyond
Authors: Dema Barbara , Suzuki Ryo , Rivera Juan
Published: September 2014

Immunoglobulin E (IgE) and its high-affinity receptor (FcεRI) are well-known participants in the allergic response. The interaction of allergens with FcεRI-bound IgE antibodies is an essential step in mast cell/basophil activation and the subsequent release of allergic mediators. It is known that the affinity of the interaction between an IgE antibody and an allergen may differ, raising the question of whether FcεRI can decipher these differences. If so, do the cellular and physiological outcomes vary? Are the molecular mechanisms initiated by FcεRI similarly under low- or high-affinity interactions? Could the resulting inflammatory response differ? Recent discoveries summarized herein are beginning to shed new light on these important questions. What we have learned from them is that IgE and FcεRI form a complex regulatory network influencing the inflammatory response in allergy and beyond.
A Ten-Year Retrospective Analysis of the Distribution, Use and Phenotypic Characteristics of the LAD2 Human Mast Cell Line
Authors: Kirshenbaum Arnold S. , Petrik Amy , Walsh Rosemary , Kirby Tara L. , Vepa Sury , Wangsa Danny , Ried Thomas , Metcalfe Dean D.
Published: September 2014

Background: In 2003, this laboratory published an account of the human mast cell line LAD2 (Laboratory of Allergic Diseases 2) that expressed FcεRI, responded to recombinant human stem cell factor (rhSCF) and resembled CD34+-derived human mast cells. LAD2 cells have now been distributed worldwide. To study the impact of this transfer, we analyzed the number of investigators receiving LAD2 cells and resulting publications. Methods: Records maintained in our laboratory, the Technology Transfer and Intellectual Property Office and Office of Technology Transfer, were reviewed for material transfer agreements (MTAs) and licensing agreements (LAs). Journals and impact factors were obtained from PubMed.gov by cross-referencing LAD2 and human mast cells from 2003 through November 2013. Results: Over 300 MTAs and 40 LAs were approved. LAD2 cells were shipped to over 30 countries. More than 80 papers have been published in journals with impact factors from 1.31 to 13.21. Intended uses include the study of receptors, degranulation, and cell signaling. LAD2 cells continue to express described markers and have consistent FcεR1-mediated degranulation. Conclusions: Success of the LAD2 line reflects the demand for a human mast cell line in research, the uniqueness of this cell line, and that it continues to exhibit minimal variation from its original description. We hope that the awareness of the impact of this cell line on mast cell research will encourage others to develop and distribute other similar cell lines with additional characteristics so as to address the limitations of depending on the study of cultured human mast cells from tissues.
Gaps in Meeting Nutrient Needs in Healthy Toddlers
Authors: Decsi Tamás , Lohner Szimonetta
Published: September 2014

Background: Among the potentially critical nutrients for toddlers, vitamin D, iron and long-chain polyunsaturated fatty acids (LC-PUFA) have recently gained special attention. A high prevalence of vitamin D deficiency was reported worldwide, affecting also small children. Iron deficiency and iron deficiency anaemia was described to be outstanding among children and prevalent in toddlers. The results of the few available studies investigating LC-PUFA intake in toddlers indicate that docosahexaenoic acid (DHA) intake in this age group fails to agree with current nutritional recommendations. Key Messages: Supplementation of toddlers with vitamin D in form of drops or tablets is already part of feeding recommendations in the majority of European countries. It is the responsibility of practitioners to work on the effective implementation of these recommendations in practice. Untoward nutritional habits, but also other factors such as socioeconomic background, are predictors of iron deficiency. Toddlers should receive iron-rich complementary foods. The consumption of fish should be encouraged already with complementary feeding to improve the DHA supply to infants and toddlers. In Hungary, DHA levels in breast milk are spectacularly lower than median DHA levels usually reported in the literature; therefore, more awareness of the importance of DHA intake during pregnancy should be created. Conclusion: There is a need to address potentially critical nutrients for toddlers and young children in Europe, such as vitamin D, iron and n-3 PUFA.
National Registries of Rare Diseases in Europe: An Overview of the Current Situation and Experiences
Authors: Taruscio Domenica , Vittozzi Luciano , Choquet Remy , Heimdal Ketil , Iskrov Georgi , Kodra Yllka , Landais Paul , Posada Manuel , Stefanov Rumen , Steinmueller Christiane , Swinnen Elfriede , Van Oyen Herman
Published: September 2014

The European Union (EU) policy for healthcare requires the establishment of a system of European Reference Networks, union-wide information databases, and registries for rare diseases (RDs) based on shared criteria. In pursuing its goals, the ‘Building Consensus and Synergies for the EU Registration of RD Patients in Europe' (EPIRARE) project convened a meeting with experts of the competent health authorities to discuss the role of national institutional RD patient registries in supporting EU patient registration and the room for international cooperation. With this aim, this paper comparatively analyses the current situation of national institutional RD registries in the EU.
Male Horse Meiosis: Metaphase I Chromosome Configuration and Chiasmata Distribution
Authors: Al-Jaru Ayman , Goodwin William , Skidmore Julian , Raudsepp Terje , Khazanehdari Kamal
Published: September 2014

Chromosome configurations and chiasma frequency during the metaphase I stage of spermatogenesis in the male horse are characterized in this work. The genome-wide frequency and distribution of chiasmata was detected as 49.45 ± 2.07 for 14 fertile stallions. All X and Y chromosomes shared a single chiasma at their pseudoautosomal region, while 1-4 chiasmata were observed in autosomal chromosomes. The chiasma frequency and distribution were further studied for 8 different bivalents identified by FISH in 5 fertile stallions. Genetic length was calculated from chiasmata data for the whole genome as well as for these 8 chromosomes. The findings complement the genetic linkage data and provide insight into the genetic basis of spermatogenesis in normal stallions.
Alteration of ZnT5-Mediated Zinc Import into the Early Secretory Pathway Affects the Secretion of Growth Hormone from Rat Pituitary Cells
Authors: Petkovic Vibor , Miletta Maria Consolata , Eblé Andrée , Flück Christa E. , Mullis Primus-E.
Published: September 2014

Background: Aggregation of growth hormone (GH) required for its proper storage in granules is facilitated by zinc (Zn2+) transported by specific zinc transporters in and out of the regulated secretory pathway. Slc30a5 (ZnT5) was reported to have the highest gene expression among all zinc transporters in primary mouse pituitary cells while ZnT5-null mice presented with abnormal bone development and impaired growth compared to wild-type counterparts. Methods: In vitro studies performed in GH3 cells, a rat pituitary cell line that endogenously produces rat GH (rGH), included analysis of: cytoplasmic Zn2+ pool changes after altering rSlc30a5 expression (luciferase assay), rZnT5 association with different compartments of the regulated secretory pathway (confocal microscopy), and the rGH secretion after rSlc30a5 knock-down (Western blot). Results: Confocal microscopy demonstrated high co-localization of rZnT5 with ER and Golgi (early secretory pathway) while siRNA-mediated knock-down of rSlc30a5 gene expression led to a significant reduction in rGH secretion. Furthermore, altered expression of rSlc30a5 (knock-down/overexpression) evoked changes in the cytoplasmic Zn2+ pool indicating its important role in mediating Zn2+ influx into intracellular compartments of the regulated secretory pathway. Conclusion: Taken together, these results suggest that ZnT5 might play an important role in regulated GH secretion that is much greater than previously anticipated.
Enhanced Autophagy by Everolimus Contributes to the Antirestenotic Mechanisms in Vascular Smooth Muscle Cells
Authors: Tang Bo , Dong Xuesong , Wei Zheng , Qiao Haiquan , Jiang Hongchi , Liu Bing , Sun Xueying
Published: September 2014

Objective: The present study aims to investigate the underlying mechanisms accounting for the activities of everolimus to inhibit the growth of vascular smooth muscle cells (VSMCs), which contributes to restenosis. Methods: Primary VSMCs were cultured in media containing smooth muscle growth supplements and incubated with testing agents. Cell proliferation, cell cycle distribution, apoptosis and autophagy, and the key molecules involved, were examined. Results: Everolimus inhibited the proliferation of VSMCs by inhibiting the activation of ribosomal protein S6 kinase and phosphorylation of eukaryotic translation initiation factor 4E-binding protein 1, and downregulating proliferating cellular nuclear antigen. Everolimus induced cell cycle arrest at the G1 phase by downregulating cyclin D1 and upregulating p27, and increased apoptosis by downregulating Bcl-2, upregulating Bad and activating capsase-3 and poly ADP ribose polymerase. Everolimus enhanced autophagy by increasing the conversion of microtubule-associated protein 1 light chain 3 (LC3)-I to LC3-II, and upregulating Beclin 1. Specific autophagy inhibitors, 3-methyladenine and bafilomycin A1, significantly attenuated the inhibition of cell proliferation, the increased apoptosis and the altered expression of the above key proteins induced by everolimus. Conclusions: Enhanced autophagy by everolimus contributes to its antirestenotic activity and its abilities to inhibit cell proliferation and to induce apoptosis of VSMCs.