bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonallergic Rhinitis in the Elderly: A Reliable and Safe Therapeutic Approach
Authors: Cantone Elena , Marino Anna , Ferranti Immacolata , Iengo Maurizio
Published: June 2015

Objective: Nonallergic rhinitis (NAR) causes significant functional and emotional impairment, affecting the quality of life (QoL) of elderly patients often suffering from other chronic diseases that require additional therapies to be added to the numerous daily medications. This study aimed to evaluate the effectiveness of crenotherapy with sodium chloride sulfate hyperthermal water rich in mineral salts on the QoL of elderly patients with NAR. Methods: Sixty elderly subjects with NAR were divided into 2 groups. Group I (n = 30) underwent crenotherapy with sodium chloride sulfate hyperthermal water rich in mineral salts, and group II (n = 30) underwent treatment with NaCl 0.9%. At baseline and after treatment, both groups underwent nasal endoscopy, and we determined their Visual Analogue Scale (VAS) scores for rhinorrhea, respiratory obstruction and sneezing. Results: After treatment, the patients in both groups reported having no adverse reactions. Endoscopic and VAS score results were better in group I than in group II. All subjects showed a good degree of tolerability. Conclusions: Our data suggest that crenotherapy improves the QoL in elderly patients with NAR. Crenotherapy can prevent elderly patients with NAR from having to take additional medications, which can often cause relevant adverse reactions and considerable health care costs.
Pre-Sleep and Sleeping Platform Construction Behavior in Captive Orangutans (Pongo spp.): Implications for Ape Health and Welfare
Authors: Samson David R. , Shumaker Rob
Published: June 2015

The nightly construction of a ‘nest' or sleeping platform is a behavior that has been observed in every wild great ape population studied, yet in captivity, few analyses have been performed on sleep related behavior. Here, we report on such behavior in three female and two male captive orangutans (Pongo spp.), in a natural light setting, at the Indianapolis Zoo. Behavioral samples were generated, using infrared cameras for a total of 47 nights (136.25 h), in summer (n = 25) and winter (n = 22) periods. To characterize sleep behaviors, we used all-occurrence sampling to generate platform construction episodes (n = 217). Orangutans used a total of 2.4 (SD = 1.2) techniques and 7.5 (SD = 6.3) actions to construct a sleeping platform; they spent 10.1 min (SD - 9.9 min) making the platform and showed a 77% preference for ground (vs. elevated) sleep sites. Comparisons between summer and winter platform construction showed winter start times (17:12 h) to be significantly earlier and longer in duration than summer start times (17:56 h). Orangutans should be provisioned with seasonally appropriate, high quality materials suitable for construction of sleeping platforms to increase sleep quality and improve animal health and welfare.
Long-Term Exposure to House Dust Mite Leads to the Suppression of Allergic Airway Disease Despite Persistent Lung Inflammation
Authors: Bracken Sonali J. , Adami Alexander J. , Szczepanek Steven M. , Ehsan Mohsin , Natarajan Prabitha , Guernsey Linda A. , Shahriari Neda , Rafti Ektor , Matson Adam P. , Schramm Craig M. , Thrall Roger S.
Published: June 2015

Background: Allergic asthma is a major cause of worldwide morbidity and results from inadequate immune regulation in response to innocuous, environmental antigens. The need exists to understand the mechanisms that promote nonreactivity to human-relevant allergens such as house dust mite (HDM) in order to develop curative therapies for asthma. The aim of our study was to compare the effects of short-, intermediate- and long-term HDM administration in a murine asthma model and determine the ability of long-term HDM exposure to suppress allergic inflammation. Methods: C57BL/6 mice were intranasally instilled with HDM for short-term (2 weeks), intermediate-term (5 weeks) and long-term (11 weeks) periods to induce allergic airway disease (AAD). The severity of AAD was compared across all stages of the model via both immunological and pulmonary parameters. Results: Short- and intermediate-term HDM exposure stimulated the development of AAD that included eosinophilia in the bronchoalveolar lavage fluid (BALF), pronounced airway hyperreactivity (AHR) and evidence of lung inflammation. Long-term HDM exposure promoted the suppression of AAD, with a loss of BALF eosinophilia and AHR despite persistent mononuclear inflammation in the lungs. Suppression of AAD with long-term HDM exposure was associated with an increase in both Foxp3+ regulatory T cells and IL-10-positive alveolar macrophages at the site of inflammation. Conclusions: This model recapitulates the key features of human asthma and may facilitate investigation into the mechanisms that promote immunological tolerance against clinically relevant aeroallergens.
The Contribution of Germinal Mosaicism to Human Aneuploidy
Authors: Ghevaria Harita , SenGupta Sioban , Sarna Urvashi , Sargeant Susannah , Serhal Paul , Delhanty Joy
Published: June 2015

Germinal mosaicism in a parent is considered to be a rare cause of aneuploidy in the offspring. The aim of this study was to assess the incidence of pre-meiotic errors, indicative of germinal mosaicism, leading to aneuploidy compared with those that occur at meiosis I. The material consisted of 126 oocytes, unexposed to sperm, donated by 57 women with an average maternal age of 35. The oocytes were at various stages of maturity and were analysed by array comparative genomic hybridisation. Of these, 102 gave conclusive results, comprising 47 that were immature, at the germinal vesicle (GV) or metaphase I stage (MI); 34 complete metaphase II-first polar body (MII-PB) complexes together with 21 incomplete complexes. Oocytes at the GV or MI stage provide direct evidence of pre-meiotic aneuploidy. Complete MII-PB complexes with the expected reciprocal gains/losses provide information on MI errors; those with non-reciprocal gains have pre-meiotic errors. Overall, 29 oocytes were aneuploid, and the source of the error was known for 21. In 8 (from 7 women) the error was pre-meiotic consisting of 4 MI oocytes and 4 MII-PB complexes with non-reciprocal gains. The remaining 13 were the result of errors at meiosis I. Although pre-meiotic errors occurred in only 10% of informative oocytes, most notable was the fact that for those oocytes where the source of the error was known, 38% were caused by germinal mosaicism compared with 62% that were the outcome of a meiosis I error. None of the women with germinal mosaicism were infertile.
Workload and Quality of Life of Medical Doctors in the Field of Oncology in Germany - a Survey of the Working Group Quality of Life of the AIO for the Study Group of Internal Oncology
Authors: Hipp Matthias , Pilz Lothar , Al-Batran Salah E. , Hautmann Matthias G. , Hofheinz Ralf-Dieter
Published: June 2015

Background: An increasing number of surveys have investigated professional stress and satisfaction among oncologists. Coevally, structural development has changed the oncological working environment. This survey investigated the quality of life and job stress among German oncological physicians. Methods: A 48-item questionnaire, which included the ‘Stress questionnaire of physicians and nurses' (FBAS), was developed by the ‘Quality of life' working group of the Internal oncology study group (AIO), and distributed anonymously at the annual meeting of the AIO working group in 2010. Descriptive statistics as well as univariate and multivariate analysis were performed. Results: 261 oncologists, mostly male (64%), older than 40 years (38%), and medical specialists (78%), took part in the survey. ‘Structural conditions' were identified as causing the highest mean stress levels, followed by ‘professional and private life'. Female participants showed a significantly lower global quality of life than male participants (p = 0.020). ‘Structural conditions' induced more stress among younger oncologists < 50 years old (p < 0.001). Qualification status was influenced by gender (p < 0.001); the multivariate analysis described the dependence of gender (p = 0.0045), working situation (p = 0.0317) and global stress (p = 0.0008). Conclusion: Structural conditions, age younger than 50 years and female gender were identified as stress risk factors among the AIO members, and showed that job stress is present in German oncology. Further research is warranted to develop evidence-based intervention strategies.
Glucagon-Like Peptide-1 Receptor Activation Does Not Affect Re-Endothelialization but Reduces Intimal Hyperplasia via Direct Effects on Smooth Muscle Cells in a Nondiabetic Model of Arterial Injury
Authors: Eriksson Linnea , Saxelin Robert , Röhl Samuel , Roy Joy , Caidahl Kenneth , Nyström Thomas , Hedin Ulf , Razuvaev Anton
Published: June 2015

Diabetic patients have an increased risk of restenosis and late stent thrombosis after angioplasty, i.e. complications that are related to a defective re-endothelialization. Exendin-4, a stable glucagon-like peptide (GLP)-1 receptor agonist, has been suggested to influence the formation of intimal hyperplasia and to increase endothelial cell proliferation in vitro. Thus, the aim of this study was to investigate the mechanisms by which treatment with exendin-4 could influence re-endothelialization and intimal hyperplasia after vascular injury. Methods: Sprague-Dawley rats were subjected to balloon injury of the left common carotid artery and treated for 4 weeks with exendin-4 or vehicle. Intimal hyperplasia and vessel wall elasticity were monitored noninvasively by high-frequency ultrasound, and re-endothelialization was evaluated upon sacrifice using Evans blue dye. Results and Conclusion: Exendin-4 selectively reduced the proliferation of smooth muscle cells (SMCs) and intimal hyperplasia in vivo without affecting the re-endothelialization process, but treatment with exendin-4 improved arterial wall elasticity. Our data also show that exendin-4 significantly decreased the proliferation and increased the apoptosis of SMCs in vitro, effects that appear to be mediated through cAMP signaling and endothelial nitric oxide synthase following GLP-1 receptor activation. Together, these effects of exendin-4 are highly desirable and may lead to an improved outcome for patients undergoing vascular interventions.
Diagnosing Pathological Prognostic Factors in Retinoblastoma: Correlation between Traditional Microscopy and Digital Slides
Authors: Zoroquiain Pablo , Logan Patrick , Bravo-Filho Vasco , Vila Natalia , Jabbour Samir , Orellana Maria Eugenia , Burnier Miguel N.
Published: June 2015

Objective: It was the aim of this study to determine the diagnostic accuracy of high-risk prognostic factors and morphological characteristics of retinoblastomas using digital whole slide images (WSI) generated by a scanner. Methods: Forty-seven H&E sections of glass slides with high-risk morphological features of retinoblastoma were analyzed. Slides were scanned as WSI and reviewed. The results were compared with those obtained after reviewing the slides using a regular microscope as the gold standard. McNemar's test (MT), the percentage of agreement (POA), and sensitivity (S) and specificity (Sp) were evaluated between WSI and conventional microscopy. Results: There were no differences with respect to multicentricity, growth type, rosette formation, choroidal invasion, anterior chamber invasion, extraocular extension, scleral extension, optic nerve invasion, necrosis, or Azzopardi effect between WSI analysis and light microscopy (MT, p = 1.0; POA = 100%; S = 100%, and Sp = 100%). Discordance was found in 1 case where calcification could not be found using WSI (MT, p = 1.00; POA = 97.9%; S = 100%, and Sp = 97.8%). Conclusion: To the best of our knowledge, this is the first report using digital pathology (WSI) to evaluate prognostic factors in eyes containing retinoblastomas. Using WSI, the pathologist was able to detect high-risk morphological features in retinoblastoma. To date, WSI is an important tool, in particular for ophthalmic pathologists examining enucleation and exenteration specimens.
The Relationship between Total Water Intake and Cognitive Control among Prepubertal Children
Authors: Khan N.A. , Raine L.B. , Drollette E.S. , Scudder M.R. , Cohen N.J. , Kramer A.F. , Hillman C.H.
Published: June 2015

Background: Cognitive control (also known as executive function) encompasses mental processes that underlie goal-directed behavior, and it enables us to adjust our behavior according to changing environmental demands. Previous research among children has demonstrated that aerobic fitness and obesity have contrasting and selective effects on cognitive control. However, the relationship between water intake and childhood cognitive control remains inadequately studied. This study investigated the relationship between total water intake and cognitive control among prepubertal children (8-9-year olds). Methods: Children between 8 and 9 years of age (n = 63) performed a modified flanker task to assess cognitive control related to inhibition (ability to resist distractions and maintain focus). Diet was measured using 3-day food records. Total water was defined as water consumed from drinking water, beverages, and food. Results: A comparison of task performance across the median intake of total water revealed that children above the median exhibited shorter reaction times across multiple conditions of the flanker task, requiring variable amounts of cognitive control. Further, after adjustment of age, IQ, socioeconomic status, weight status, and aerobic fitness level, the proportion of intake comprised of water (%TW) was negatively correlated with reaction time interference, that is, the ability to maintain task performance when task conditions demanded greater inhibition. Conclusions: These results indicate an association between water intake and cognitive control using a task that modulates inhibition. Specifically, higher water intake correlated with greater ability to maintain task performance when inhibitory demands are increased. Future work is needed to determine the mechanism by which water influences cognitive control among children.
Clinical Relevance of Cluster Analysis in Phenotyping Allergic Rhinitis in a Real-Life Study
Authors: Bousquet Philippe Jean , Devillier Philippe , Tadmouri Abir , Mesbah Kamal , Demoly Pascal , Bousquet Jean
Published: June 2015

Background: Disease stratification, using phenotypic characterization performed either by hypothesis- or data-driven methods, was developed to improve clinical decisions. However, cluster analysis has not been used for allergic rhinitis. Objective: To define clusters in allergic rhinitis and to compare them with ARIA (Allergic Rhinitis and Its Impact on Asthma), a hypothesis-driven approach. Methods: A French observational prospective multicenter study (EVEIL: Echelle visuelle analogique dans la rhinite allergique) was carried out on 990 patients consulting general practitioners for allergic rhinitis and treated as per clinical practice. In this study, changes in symptom scores, visual analogue scales and quality of life were measured at baseline and after 14 days of treatment. A post hoc analysis was performed to identify clusters of patients with allergic rhinitis - using Ward's hierarchical method - and to define their clinical relevance at baseline and after 14 days of treatment. The cluster approach was compared to the ARIA approach. Results: Patients were clustered into 4 phenotypes which partly followed the ARIA classes. These phenotypes differed in their disease severity including symptoms and quality of life. Physicians in real-life practice prescribed medication regardless of the phenotype and severity, with the exception of patients with ocular symptoms. Prescribed treatments were comparable in hypothesis- and data-driven analyses. The prevalence of uncontrolled patients during treatment was similar in the 4 clusters, but was significantly different according to the ARIA classes. Conclusion: Cluster analysis using demographic and clinical parameters only does not appear to add relevant information for disease stratification in allergic rhinitis.
Radical Improvement of Signs and Symptoms in Systemic Lupus Erythematosus when Treated with Hemodiafiltration with Endogenous Reinfusion Dialysis
Authors: Solano Francesco Giuseppe , Bellei Elisa , Cuoghi Aurora , Caiazzo Marialuisa , Bruni Francesco
Published: June 2015

Lupus nephritis is one of the most serious complications of systemic lupus erythematosus (SLE). In the kidney, immune complexes and autoantibodies activate mesangial cells that secrete cytokines that can further amplify inflammatory processes. We present the case of a 42-year-old woman with lupus nephritis accompanied by periods of exacerbation of SLE, with necrotic-like skin lesions, psoriatic arthritis without skin psoriasis, purpura of the lower limb, petechial rash, joint pain, fever, eyelid edema with bilateral conjunctival hyperemia and itching. The patient underwent a dialytic treatment of hemodiafiltration with endogenous reinfusion. The technique uses the super-high-flux membrane Synclear 02 (SUPRA treatment) coupled with an adsorbent cartridge that has affinity for many toxins and mediators. Fever and joint pain were immediately reduced after treatment and, subsequently, there was a notable reduction of the skin damage. Prednisone and immunosuppressive drugs were gradually reduced until complete suspension. High-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometer was performed for identification of proteins captured by a resin bed during a dialysis session of the patient. This technique identified several biomarkers of kidney injuries, uremic toxins, fragments of immunoglobulins, antigens involved in antiphospholipid syndrome and a new marker (α-defensin) that correlated significantly with disease activity. The removal of these different proteins could possibly provide an explanation of the improvement in the patient's symptoms and the normalization of her SLE. SUPRA coupled with an adsorption may be a promising new technique for the treatment of lupus nephritis.
A Ten-Year Longitudinal Study of Caries among Patients Aged 14-72 Years in Norway
Authors: Dobloug Andreas , Grytten Jostein
Published: June 2015

There are few longitudinal studies in which the development of caries over a long period of time has been studied for different age groups. Such studies are important because they can provide information to assess future needs for dental care and the implications if the development of caries is different for patients in different age groups. We describe changes in caries during the period 2003-2012 for several birth cohorts in Norway, using longitudinal data collected annually for each individual during a period of 10 years. The data set included patients born during the period 1940-1989 who received regular dental care in the public dental services in the county of Hedmark - altogether 7,519 patients. Information about caries was obtained from the electronic patient records. Nearly 90% of the patients had no caries for at least 5 years during the 10-year study period, and nearly 50% had no caries for at least 8 years. This pattern was similar for all birth cohorts. The mean number of carious teeth per patient decreased from 2003 to 2012. This decrease was particularly large at the end of the period and among the oldest birth cohorts, i.e. those born in the periods 1940-1949 and 1950-1959. Our findings indicate that the need for restorative treatment is reducing, particularly in the older age groups. Fewer dentists and more dental hygienists may be needed in the future to provide routine follow-up and care.
Improving the Measurement of Cognitive Ability in Geriatric Patients
Authors: Lebedeva Elena , Gallant Serge , Tsai Cheng-En , Koski Lisa
Published: June 2015

Background/Aims: No single tool is available in geriatric clinical settings to quantitatively measure global cognitive ability at different stages ranging from normal functioning to severe impairment. We developed an adaptive test to measure cognitive ability in geriatric populations (Geriatric Rapid Adaptive Cognitive Estimate, GRACE); however, the test failed to discriminate between high-functioning individuals. This study aimed to estimate the extent to which adding more difficult items to the GRACE would improve measurement precision in the upper range of cognitive ability. Methods: The original data used to develop the GRACE was merged with newly collected data of patients who presented at local geriatric clinics. The Rasch analysis was used to estimate the difficulty level of the newly added items and evaluate whether the psychometric properties of the GRACE were improved. Results: One newly added item (Sequencing 5) had a higher difficulty level than all of the previous items in the GRACE. The rest of the new items were located in the high difficulty range. Conclusion: The psychometric properties of our adaptive screening tool were improved, and we were able to distinguish between individuals who had higher levels of cognitive functioning.
Fetal Erythroblastosis May Be an Indicator of Neonatal Transient Hyperinsulinism
Authors: Mizumoto Hiroshi , Iki Yoichi , Yamashita Sumie , Kawai Masahiko , Katayama Toshiro , Hata Daisuke
Published: June 2015

Background: Small for gestational age and birth asphyxia are associated with neonatal transient hyperinsulinism (THI). Some newborns with THI showed marked erythroblastosis on admission to our neonatal intensive care unit. Objective: This study was designed to test our hypothesis that fetal erythroblastosis may be a risk factor for developing THI. Methods: The records of all babies admitted to our neonatal intensive care unit within 24 h of birth between January 2010 and May 2014, and who were born after 34 weeks of gestation, were retrospectively reviewed. Hyperinsulinism was diagnosed as hypoglycemia concomitant with high serum insulin in babies requiring >6 mg/kg/min intravenous glucose and THI as hyperinsulinism without maternal diabetes or genetic disorders. The following three possible risk factors for THI were evaluated: (1) birth weight z-score, (2) 1-min Apgar score and (3) absolute nucleated red blood cell (aNRBC) count on admission. Results: Of 705 infants, 8 were diagnosed with THI. Multivariate logistic regression analysis revealed that the aNRBC count was the most significant risk factor for THI. The median aNRBC count was 181/µl (interquartile range 0-538/µl), and 8 of 71 infants (11.3%) having an aNRBC count >1,413/µl (90th percentile in this study) had THI. The aNRBC counts in the 8 cases with THI were significantly higher than those in the 5 cases with hyperinsulinism caused by maternal diabetes or genetic disorders. Conclusions: This study showed that the aNRBC count was strongly associated with subsequent THI. Fetal erythroblastosis, characterized by chronic fetal hypoxia, may be an indicator of perinatal stress sufficient to cause THI.
The Effect of Ptosis on Cataract Surgical Planning
Authors: Kuo Irene C.
Published: June 2015

Purpose: To describe a patient complaining of ‘ghosting' and ‘shadowing' after bilateral, sequential cataract extraction with toric intraocular lens (IOL) implantation who was found to have significant eyelid ptosis. Methods: The following is a case report. Results: The patient's complaints arose a few weeks after surgery. By the second postoperative month, the patient's keratometry had changed compared to preoperative measurements. Because of significant ptosis, the patient underwent upper eyelid surgery. Four months later, he was found to have less corneal astigmatism than had been measured prior to cataract surgery. Following 2 stable examinations, a Prevue lens based on Hartmann-Shack wavefront aberrometry was made for each eye, which the patient said significantly improved his quality of vision. Wavefront-guided photorefractive keratectomy (PRK) was performed 6 months after cataract surgery. One year after PRK, the patient's symptoms had disappeared, his uncorrected visual acuity was 20/20 in the right eye and 20/15 in the left, and he was satisfied with his quality of vision. Conclusions: Bilateral toric IOLs were implanted in this patient based on measurements of corneal astigmatism that changed after cataract surgery and changed further after ptosis repair. This case demonstrates the importance of evaluating eyelid position in cataract surgical planning as ptosis can contribute significantly to corneal astigmatism. Patient education is important in the setting of higher expectations from purchase of premium lens implants.
Vitamin D Status and Adiposity in Pediatric Malabsorption Syndromes
Authors: Nwosu Benjamin Udoka , Maranda Louise
Published: June 2015

Background: The combined effects of nutrient malabsorption and adiposity on vitamin D status are unclear in pediatric malabsorption syndromes. Aim: To determine the relationship between adiposity and serum 25-hydroxyvitamin D (25(OH)D) in malabsorption disorders. Methods: Prepubertal children of ages 3-12 with either lactose intolerance (LI) (n = 38, age 8.61 ± 3.08, male/female 19/19), or celiac disease (CD) (n = 24) were compared to healthy controls (n = 49, age 7.95 ± 2.64, male/female 28/21). A separate cohort of combined prepubertal and pubertal subjects with inflammatory bowel disease (IBD) (n = 59, age 16.4 ± 2.2, male/female 31/27) were also compared to healthy controls (n = 116, male/female 49/67, age 14.6 ± 4.4). Vitamin D deficiency was defined as 25(OH)D of <50 nmol/l, overweight as body mass index (BMI) of ≥85th but <95th percentile, and obesity as BMI ≥95th percentile. Results: Among the controls, 25(OH)D was significantly higher in the normal-weight prepubertal controls vs. the overweight/obese controls (p = 0.001), and similarly so for the combined cohort of prepubertal and pubertal controls (p = 0.031). In contrast, there was no significant difference in 25(OH)D concentration between the normal-weight vs. overweight/obese patients with LI (p = 0.335), CD (p = 0.387), and IBD (p = 0.883). Conclusion: There is no association between adiposity and serum 25(OH)D in pediatric malabsorption syndromes.
The Co-Expression of Kallikrein 5 and Kallikrein 7 Associates with Poor Survival in Non-HPV Oral Squamous-Cell Carcinoma
Authors: Leusink Frank K.J. , van Diest P.J. , Frank M.H. , Broekhuizen R. , Braunius W. , van Hooff S.R. , Willems Stefan M. , Koole R.
Published: June 2015

Objective: Oral squamous-cell carcinoma (OSCC) still has a poor prognosis. Lymph node metastasis (LNM) is a major determinant of treatment decisions and prognosis. Serine protease inhibitor Kazal-type 5 (SPINK5) is the inhibitor of kallikrein 5 (KLK5) and KLK7. SPINK5, KLK5 and KLK7 are three of the genes of a recently validated LNM-predicting gene expression profile in OSCC. This study evaluates their clinicopathological role and value as biomarkers in OSCC. Methods: Eighty-three patients with primary OSCC, treated surgically between 1996 and 2000, were included. Gene expression data were acquired from a previously reported study. Human papillomavirus (HPV) status was determined by an algorithm for HPV-16. Protein expression for KLK5, KLK7 and SPINK5 was semi-quantitatively determined in all 83 tumours by immunohistochemistry. All expression data were correlated with clinicopathological parameters. Results: Concurrent loss of KLK5 and KLK7 correlates with worse disease-specific and overall survival (DSS and OS). Multivariate analysis proved that co-expression is an independent prognostic factor for DSS (p = 0.029) and OS (p = 0.001). Conclusion: This report demonstrates that concurrent loss of KLK5 and KLK7 associates with a poor clinical outcome in OSCC and could therefore serve as prognostic marker in this disease.
A New Three-Dimensional Template for the Fabrication and Localization of an Autogenous Cartilage Framework during Microtia Reconstruction
Authors: Chen Keguang , Fu Yaoyao , Yang Lin , Dai Peidong , Zhang Tianyu
Published: June 2015

Aims: To assist with the accurate fabrication and localization of a costal cartilage framework for auricular reconstruction, three-dimensional (3D) digital and solid templates including the auricle and guide plate were made for microtia patients. Methods: The computed tomography data of 60 patients with microtia were included. The 3D digital template of the auricle and guide plate on the healthy side was shaped using MIMICS software with graphic image processing and 3D reconstruction technology. The 3D digital template on the affected side was produced by mirror technique and made into a solid template for clinical application. Results: All 60 patients had a good result of the location and the appearance of the constructed auricle. The time of operation was decreased by an average of half an hour. An individualized 3D solid model of the reconstructed auricular template on the affected side was successfully produced and used in auricular reconstruction. Conclusions: The new 3D template of the auricle and guide plate may be a major contribution to the engraving, assembling and localization of the microtia auricle in auricular reconstruction.
Facial Onset Sensory and Motor Neuronopathy: Further Evidence for a TDP-43 Proteinopathy
Authors: Ziso Besa , Williams Tim L. , Walters R. Jon L. , Jaiser Stephan R. , Attems Johannes , Wieshmann Udo C. , Larner A.J. , Jacob Anu
Published: June 2015

Three patients with the clinical and investigation features of facial onset sensory and motor neuronopathy (FOSMN) syndrome are presented, one of whom came to a post-mortem examination. This showed TDP-43-positive inclusions in the bulbar and spinal motor neurones as well as in the trigeminal nerve nuclei, consistent with a neurodegenerative pathogenesis. These data support the idea that at least some FOSMN cases fall within the spectrum of the TDP-43 proteinopathies, and represent a focal form of this pathology.
DD Genotype of ACE I/D Polymorphism Might Confer Protection against Dental Caries in Polish Children
Authors: Olszowski Tomasz , Adler Grażyna , Janiszewska-Olszowska Joanna , Safranow Krzysztof , Chlubek Dariusz
Published: June 2015

The aim of the study was to examine the frequencies of the genotypes and alleles of ACE insertion/deletion (I/D) polymorphism and their association with dental caries in a sample of Polish children. The study subjects were 120 children with dental caries experience (cases) and 41 caries-free individuals (controls). The genotyping was performed using polymerase chain reaction. The genotype distributions of ACE I/D polymorphism were not statistically different between carious and control children. However, we found a borderline overrepresentation of the II + ID genotypes versus the DD genotype in the carious compared to the control group (69.2% and 51.2%, respectively, p = 0.057). Logistic regression analysis adjusted for age and sex revealed that I allele carriage was a significant predictor of dental caries susceptibility (OR = 2.14, 95% CI = 1.02-4.49, p = 0.041). In conclusion, the DD genotype of ACE I/D polymorphism might be protective against dental caries in Polish children.
Inhibition of Glutathione S-Transferase by Ethacrynic Acid Augments Ischemia-Reperfusion Damage and Apoptosis and Attenuates the Positive Effect of Ischemic Postconditioning in a Bilateral Acute Hindlimb Ischemia Rat Model
Authors: Nagy Tibor , Kovács Viktória , Hardi Péter , Veres Tünde Gyöngyvér , Takács Ildikó , Jancsó Gábor , Sinay László , Fazekas Gábor , Pintér Örs , Arató Endre
Published: June 2015

Aims: We studied the effects of the inhibition of the endogene antioxidant glutathione-S-transferase (GST) by ethacrynic acid (EA) on ischemia-reperfusion (IR) injury and postconditioning (PC) in the lower extremities. We aimed to examine the oxidative stress parameters (OSP), inflammatory response and activation of proapoptotic signaling proteins (PSP) after revascularization surgery. Methods: Sixty Wistar rats were divided into 6 groups: control, IR, PC, EA-control, IR and administration of EA (IR/EA) and PC and administration of EA (PC/EA). The IR, PC, IR/EA and PC/EA groups underwent 60 min of infrarenal aortic cross-clamping. After that, PC was performed in the PC and PC/EA groups. In 3 of the groups, the animals were treated with EA (EA-control, IR/EA and PC/EA groups) as well. The ischemia was followed by 120 min of reperfusion. Blood samples and biopsy specimens were collected from the quadriceps muscle. Plasma malondialdehyde, reduced glutathione, thiol/sulfhydryl group levels, TNF-α and IL-6 concentrations and superoxide-dismutase enzyme activity were measured. Results: The levels of the OSP and the inflammatory proteins were higher in the EA-administered groups. The ratio of phosphorylated PSP was higher in the EA-administered groups and the protective effect of PC did not develop. Conclusions: Inhibition of GST by EA augmented the IR damage. GST inhibition was associated with a different activation of the mitogen-activated protein kinases and the PSP, regulating these pathways in the process of apoptosis and PC.
Vivid Mental Imagery of Biomechanically Impossible Movements Elicited by Cortical Electrostimulation of the Central Region in an Awake Patient
Authors: Gayoso García Sonia , Herbet Guillaume , Duffau Hugues
Published: June 2015

Background: The perception we have of our own body, called ‘body image,' is crucial for self-awareness. Here, we evoked reproducible mental imagery of a postural illusion by intrasurgical electrostimulation of the central cortex. Case Report: A 24-year-old patient experienced seizures involving vivid mental imagery of biomechanically impossible movements of the upper limb. A right precentral low-grade glioma was diagnosed. Awake surgery with intraoperative electrostimulation sensorimotor mapping was performed. Remarkably, the same mental representations of biomechanically impossible movements of the left upper limb were repeatedly elicited during stimulation of the central cortex. These eloquent areas were preserved, even though the precentral part of the knob of the hand was removed. After a transient monoplegia, the patient recovered and resumed a normal life which included playing the guitar. Conclusion: These mental experiences of a postural illusion generated by intraoperative stimulation could be related to neuroplasticity mechanisms induced by the slow growth of low-grade glioma within the knob of the hand. Such a functional reorganization may explain why this area was removed without permanent deficits. This perception of biomechanically impossible movements during surgery might be due to a transient disruption by stimulating the frontoparietal network involved in the coding of the body image.
Prone Position Is Useful in Thoracoscopic Enucleation of Esophageal Leiomyoma
Authors: Maki Kenji , Takeno Shinsuke , Nimura Satoshi , Yamana Ippei , Shimaoka Hideki , Hashimoto Tatsuya , Shibata Ryousuke , Shiwaku Hironari , Yamashita Kanefumi , Yamashita Yuichi
Published: June 2015

A 36-year-old man was admitted to our institute due to the diagnosis of esophageal submucosal tumor detected by a periodical upper gastrointestinal endoscopic examination without any complaint. Thoracoscopic enucleation of the lesion with the preoperative clinical diagnosis of esophageal leiomyoma was performed under general anesthesia in the prone position. After immunohistochemical examination, the pathological diagnosis was leiomyoma. There was no remarkable event during the postoperative hospital stay, and the patient was discharged on the 12th day after surgery. This case report suggests that the prone position might be superior to the left lateral decubitus position in thoracoscopic enucleation of esophageal leiomyoma.
Daclatasvir, Simeprevir and Ribavirin as a Promising Interferon-Free Triple Regimen for HCV Recurrence after Liver Transplant
Authors: Herzer Kerstin , Papadopoulos-Köhn Angela , Walker Andreas , Achterfeld Anne , Paul Andreas , Canbay Ali , Timm Jörg , Gerken Guido
Published: June 2015

Background: Recurrent hepatitis C infection after liver transplantation (LT) is associated with lower rates of graft and patient survival. Methods: Here we describe the first use of daclatasvir, simeprevir, and ribavirin (RBV) as an all-oral triple regimen administered to 6 liver transplant recipients with recurrent hepatitis C, one with GT 1a and 5 with GT 1b. All patients were treated for 24 weeks. Trough levels of immunosuppression, laboratory measures, and potential adverse effects were closely monitored. Results: For all patients, viral load became undetectable between treatment weeks 4 and 12. One patient experienced a viral breakthrough at the 10th week of treatment; this was associated with the selection of resistance-associated variants (D168Y in NS3 and ΔP32 in NS5A). For the other 5 patients, end-of-treatment response and for 4 patients SVR24 was achieved. Viremia recurred in one patient 4 weeks after the end of treatment, which was again associated with the selection of resistance-associated variants (D168V in NS3 and ΔP32 in NS5A). Clinical measures of liver function improved substantially for all patients. Adverse events were few and limited to moderate anemia caused by RBV. Importantly, adjustments to the immunosuppressant dosage were not required. Conclusions: The described regimen appears to be safe and effective for liver transplant patients and will be a promising treatment regimen for post-LT patients.
Mortality and Longevity after a Spinal Cord Injury: Systematic Review and Meta-Analysis
Authors: Chamberlain Jonviea D. , Meier Sonja , Mader Luzius , von Groote Per M. , Brinkhof Martin W.G.
Published: June 2015

Background/Aims: Mortality and longevity studies of spinal cord injury (SCI) are essential for informing healthcare systems and policies. This review evaluates the current evidence among people with SCIs worldwide in relation to the WHO region and country income level; demographic and lesion characteristics; and in comparison with the general population. Methods: A systematic review of relevant databases for original studies. Pooled estimates were derived using random effects meta-analysis, restricted to traumatic SCI. Results: Seventy-four studies were included. In-hospital mortality varied, with pooled estimates of 24.1% (95% confidence interval (CI) 14.1-38.0), 7.6% (95% CI 6.3-9.0), 7.0% (95% CI 1.5-27.4), and 2.1% (95% CI 0.9-5.0) in the WHO regions of Africa, the Americas, Europe and Western Pacific. The combined estimate for low- and middle-income countries was nearly three times higher than for high-income countries. Pooled estimates of first-year survival were 86.5% (95% CI 75.3-93.1), 95.6% (95% CI 81.0-99.1), and 94.0% (95% CI 93.3-94.6) in the Americas, Europe and Western Pacific. Pooled estimates of standardized mortality ratios in tetraplegics were 2.53 (2.00-3.21) and 2.07 (1.47-2.92) in paraplegics. Conclusion: This study found substantial variation in mortality and longevity within the SCI population, compared to the general population, and between WHO regions and country income level. Improved standardization and quality of reporting is needed to improve inferences regarding the extent to which mortality outcomes following an SCI are related to healthcare systems, services and policies.
Effect of EphA7 Silencing on Proliferation, Invasion and Apoptosis in Human Laryngeal Cancer Cell Lines Hep-2 and AMC-HN-8
Authors: Xiang Cheng , Lv Yuanjing , Wei Yanjie , Wei Jing , Miao Susheng , Mao Xionghui , Gu Xin , Song Kaibin , Jia Shenshan
Published: June 2015

Aims: This study aimed to investigate the expression of EphA7 in human laryngeal squamous cell carcinoma (LSCC) tissues and disclose the potential roles and molecular mechanisms of EphA7 in LSCC. Methods: In the present study, we examined EphA7 expression and its function and mechanism in LSCC. EphA7 expression levels were investigated by quantitative real-time PCR (qRT-PCR), western blotting, and immunohistochemistry in a panel of 35 LSCC patient cases. To investigate the potential mechanism of EphA7 in human laryngeal cancer, we employed EphA7 siRNA to knockdown EphA7 expression in LSCC cell line Hep-2 and AMC-HN-8. Subsequently, MTT, TUNEL, qRT-PCR, and western blotting were performed to disclose the roles of EphA7 on proliferation, invasion and migration, and apoptosis in LSCC cell line Hep-2 and AMC-HN-8. Results: Depletion of EphA7 remarkably inhibited the proliferation and invasion of Hep-2 and AMC-HN-8 cells in comparison to control and EphA7 siRNA negative control (NC)-transfected cells. TUNEL staining assay demonstrated that, compared with the control group, the rate of apoptosis in the EphA7 siRNA group was significantly increased. In addition, knockdown of EphA7 in Hep-2 or AMC-HN-8 cells markedly decreased the expression of EphA7 and PTEN, which could contribute to apoptosis. However, the bpV(phen), a PTEN inhibitor, could attenuate anti-proliferation and pro-apoptotic effects of EphA7 siRNA in Hep-2 and AMC-HN-8 cells. Conclusion: Up-regulation of EphA7 was observed in human LSCC samples and down-regulation of EphA7 effectively suppressed laryngeal carcinoma cell growth and promoted its apoptosis. Thus, EphA7 has a critical role in modulating cell growth and apoptosis, which serves as a potential therapeutic target in human LSCC.
Cigarette Smoke Modulates NOD1 Signal Pathway and Human ß Defensins Expression in Human Oral Mucosa
Authors: Qian Ya-jie , Wang Xiang , Gao Ya-fan , Duan Ning , Huang Xiao-feng , Sun Fang-fang , Han Xiao-dong , Wang Wen-mei
Published: June 2015

Background/Aims: Nucleotide binding oligomerization domain 1 (NOD1) signal pathway and human ß defensins (hBDs) play crucial roles in innate immune. Cigarette smoke has been confirmed to dampen innate immune in some human tissues, such as oral mucosa. The aim of this study was to evaluate potential effects of smoking on NOD1 signaling and hBDs expression in oral mucosa. Methods: Tissue specimens of normal oral mucosa were collected from donors undergoing routine surgical treatment. All 20 participants were classified equally as two groups: non-smokers and smokers. By using Western blotting and immunohistochemistry, we investigated differential expression of crucial molecules in NOD1 signal pathway, hBD-1, -2, and -3 in oral mucosa tissues between non-smokers and smokers. Immortalized human oral mucosal epithelial (Leuk-1) cells were treated with various concentrations of cigarette smoke extract (CSE) for 24h. Western blotting and immunofluorescence assays were performed to study CSE-induced alteration of protein expression. Leuk-1 cells were treated with 4% CSE, iE-DAP (NOD1 agonist), CSE + iE-DAP, BAY 11-7082 (NF-κB inhibitor), 4% CSE + BAY 11-7082, respectively. Real-time PCR and ELISA were performed to detect the mRNA levels and secretion of hBD-1, -2, and -3, respectively. Results: The levels of NOD1, NF-κB, hBD-1 and hBD-3 significantly reduced in oral mucosa tissues of smokers compared with non-smokers. The levels of RIP2 (receptor-interacting protein 2), phospho-NF-κB (P-NF-κB) and hBD-2 remarkably enhanced in oral mucosal tissues of smokers. CSE treatment suppressed NOD1 and NF-κB expression and activated RIP2 and P-NF-κB expression in Leuk-1 cells. The mRNA and secretory levels of hBD-1 and -3 were down-regulated by CSE, while the mRNA and secretory level of hBD-2 were up-regulated by CSE. The iE-DAP or BAY 11-7082 treatment reversed the regulatory effects of CSE on levels of hBDs. Conclusion: The present study indicated that cigarette smoke could potentially modulate the expression of crucial molecules of NOD1 signal pathway and hBDs in human oral mucosal epithelium. NOD1 signal pathway could play an important role in the regulatory effects of CSE on hBDs levels in oral mucosal epithelial cells.
Low Expression of miR-448 Induces EMT and Promotes Invasion by Regulating ROCK2 in Hepatocellular Carcinoma
Authors: Zhu Huaqiang , Zhou Xu , Ma Chaoqun , Chang Hong , Li Hongguang , Liu Fangfeng , Lu Jun
Published: June 2015

Background/Aims: miR-448 has been reported to exhibit abnormal expression in hepatocellular carcinoma (HCC), however, the essential role of miR-448 in HCC progression is still unclear. Methods: real-time PCR was used to detect the expression of miRNAs and candidate genes in HCC samples (n=117). miR-448 mimics and inhibitor were tansfected in human HCC cells. The transwell assay was used to examine the cell invasive ability. The regulation mechanism was confirmed by luciferase reporter assay. The markers of EMT were detected by using Western blot. Results: miR-448 was decreased in HCC samples and associated with HCC development. Inhibition of miR-448 significantly promoted cell invasion, while the effect of miR-448 up-regulation was reverse. miR-448 could regulate ROCK2 in hepatocellular carcinoma. Knockdown of ROCK2 expression partially reversed the effect of miR-448 inhibitor. Abnormal expression of miR-448 could regulate the markers of epithelial-mesenchymal transition (EMT). Conclusions: miR-448 may contribute to the progression of HCC via regulating ROCK2 expression.
Hydrogen Suppresses Hypoxia/Reoxygenation-Induced Cell Death in Hippocampal Neurons Through Reducing Oxidative Stress
Authors: Wei Rong , Zhang Rufang , Xie Yewei , Shen Li , Chen Fang
Published: June 2015

Background & Aims: Deep hypothermic circulatory arrest (DHCA) is a cerebral protection technique that has been used in the operations involving the aortic arch and brain aneurysm for decades. We previous showed that DHCA treated rats developed a significant oxidative stress and apoptosis in neurons. We here intend to investigate the protective the effect of hydrogen against oxidative stress-induced cell injury and the involved mechanisms using an in vitro experimental model of hypoxia/reoxygenation (H/R) on HT-22 cells. Methods: The model of H/R was established using an airtight culture container and the anaeropack. Measurement of mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) production was used H2DCFDA and JC-1 staining. Western blot was used for the quantification of Akt, p-Akt, Bcl-2, Bax and cleaved caspase-3 proteins. The microRNA (miRNA) profile in hippocampal neurons from rat model of DHCA was determined by miRNA deep sequencing. Results: The elevation of ROS and reduction of MMP were significantly induced by the treatment with hypoxia for 18 h followed by reoxygenation for 6 h. Hydrogen treatment significantly reduced H/R-caused cell death. The levels of p-Akt (Ser 473) and Bcl-2 were significantly increased while Bax and cleaved caspase-3 were decreased by hydrogen treatment on the model of H/R. The expression of miR-200 family was significantly elevated in model of DHCA and H/R. Hydrogen administration inhibited the H/R-induced expression of miR-200 family in HT-22 cells. In addition, inhibition of miR-200 family suppressed H/R-caused cell death through reducing ROS production. Conclusions: These results suggest that H/R causes oxidative stress-induced cell death and that the hydrogen protects against H/R-induced cell death in HT22 cells, in part, due to reducing expression of miR-200 family.