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Background: The Mucorales are an important opportunistic fungi that can cause mucormycosis in immunocompromised patients. The fast and precise diagnosis of mucormycosis is very important because, if the diagnosis is not made early enough, dissemination often occurs. It is now well established that molecular methods such as polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) are feasible and reliable tools for the early and accurate diagnosis of mucormycosis agents., Objectives: The present study was conducted to evaluate the validity of PCR-RFLP for the identification of Mucorales and some important Mucor and Lichtheimia species in pure cultures of Zygomycetes., Materials and Methods: Specific sense and anti-sense primers were used to amplify the Mucorales, Mucor, and Lichtheimia DNA. The PCR products were digested by AfIII, XmnI, and AcII restriction enzymes, and the resultant restriction pattern was analyzed., Results: On the basis of the molecular and morphological data, we identified Mucor plumbeus (10.83%), M. circinelloides (9.17%), Lichtheimia corymbifera (9.17%), M. racemosus (5.83%), M. ramosissimus (3.33%), and L. blakesleeana (0.83%)., Conclusions: It seems that PCR-RFLP is a suitable technique for the identification of Mucorales at the species level.

Background and Purpose: Soil is the main habitat of saprophytic and pathogenic fungi. Mucoromycotina constitutes a large group of soil fungi, with certain opportunistic members causing systemic infections in immunocompromised hosts. The majority of human and animal infections are caused by the members of the genera Rhizopus , Mucor , Rhizomucor , Lichtheimia ( Absidia) , Cunninghamella, and Mortierella . Accordingly, in the present study, we aimed to isolate and identify the main genera of the order Mucorales, using molecular assays and morphological features ., Materials and Methods: In total, 340 soil samples were collected from seven public parks throughout the city and sidewalk gardens in 14 municipal districts in Isfahan, Iran. All the samples were cultured on the appropriate media, incubated at 27°C for 2- 4 days, and examined daily for visible fungal growth. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was applied and macroscopic, microscopic, and physiological characteristics were assessed to identify fungal colonies., Results: 400 pure colonies, belonging to the orders Mucorales and Mortierellales, including the genera Lichtheimia , Rhizopus, Rhizomucor, Mucor, Cunninghamella, and Mortierella, were identified . The genus Rhizopus (35.5%) was the most frequent isolate, followed by Mucor (32.25%) and Rhizomucor (27.5%)., Conclusion: The results emphasize the importance of opportunistic fungi in public areas and indicate the risk of exposure for immunocompromised individuals., Competing Interests: There was no conflict of interest in the present study.

A classic example of solid-state topochemical reactions is the ultraviolet-light induced photodimerization of α-trans-cinnamic acid (CA). Here, we report the first observation of an X-ray-induced dimerization of CA and monitor it in situ using nonresonant inelastic X-ray scattering spectroscopy (NRIXS). The time-evolution of the carbon core-electron excitation spectra shows the effects of two X-ray induced reactions: dimerization on a short time-scale and disintegration on a long time-scale. We used spectrum simulations of CA and its dimerization product, α-truxillic acid (TA), to gain insight into the dimerization effects. From the time-resolved spectra, we extracted component spectra and time-dependent weights corresponding to CA and TA. The results suggest that the X-ray induced dimerization proceeds homogeneously in contrast to the dimerization induced by ultraviolet light. We also utilized the ability of NRIXS for direct tomography with chemical-bond contrast to image the spatial progress of the reactions in the sample crystal. Our work paves the way for other time-resolved studies on chemical reactions using inelastic X-ray scattering.

Adsorption geometry of dye molecules can have a substantial impact on the efficiency and functional lifespan of a dye-sensitised solar cell (DSSC) and therefore, its reliable assessment is an important step in engineering more efficient DSSCs. X-ray photoelectron spectroscopy (XPS) of oxygen is empirically proved to be the most efficient technique in distinguishing between the two most occurring adsorption geometries, i.e. monodentate and bidentate. In this computational study, we provide a comprehensive analysis of XPS and X-ray absorption spectroscopy (XAS) of carbon and oxygen for these binding modes in a perylene-sensitised TiO2. We confirm that O 1s XPS has an excellent sensitivity in mode identification. Moreover, we show that adsorption has a great impact on the XPS binding energies and reduces them by ∼4 eV, and using this effect, we extend the XPS usage to study dye desorption in the cell. Finally, our results for XAS indicate that although less sensitive, the spectra from carbon can be used in mode detection.

To accurately estimate muscle forces using electromyogram (EMG) signals, precise EMG amplitude estimation, and a modeling scheme capable of coping with the nonlinearities and dynamics of the EMG-force relationship are needed. In this work, angle-based EMG amplitude calibration and parallel cascade identification (PCI) modeling are combined for EMG-based force estimation in dynamic contractions, including concentric and eccentric contractions of the biceps brachii and triceps brachii muscles. Angle-based calibration has been shown to improve surface EMG (SEMG) based force estimation during isometric contractions through minimization of the effects of joint angle related factors, and PCI modeling captures both the nonlinear and dynamic properties of the process. SEMG data recorded during constant force, constant velocity, and varying force, varying velocity flexion and extension trials are calibrated. The calibration values are obtained at specific elbow joint angles and interpolated to cover a continuous range of joint angles. The calibrated data are used in PCI models to estimate the force induced at the wrist. The experimental results show the effectiveness of the calibration scheme, combined with PCI modeling. For the constant force, constant velocity trials, minimum %RMSE of 8.3% is achieved for concentric contractions, 10.3% for eccentric contractions and 33.3% for fully dynamic contractions. Force estimation accuracy is superior in concentric contractions in comparison to eccentric contractions , which may be indicative of more nonlinearity in the eccentric SEMG-force relationship.

Steviol glycosides (SVglys) and gibberellins are originated from the shared biosynthesis pathway in Stevia (Stevia rebaudiana Bertoni). In this research, two experiments were conducted to study the opposing effects of external gibberellin (GA3) and Daminozide (a gibberellin inhibitor) on Stevia growth and metabolites. Results showed that GA3 significantly increased the stem length and stem dry weight in Stevia. Total soluble sugar content increased while the SVglys biosynthesis was decreased by external GA3 applying in Stevia leaves. In another experiment, the stem length was reduced by Daminozide spraying on Stevia shoots. The Daminozide did not affect the total SVglys content, while in 30 ppm concentration, significantly increased the soluble sugar production in Stevia leaves. Although the gibberellins biosynthesis pathway has previously invigorated in Stevia leaf, the Stevia response to external gibberellins implying on high precision regulation of gibberellins biosynthesis in Stevia and announces that Stevia is able to kept endogenous gibberellins in a low quantity away from SVglys production. Moreover, the assumption that the internal gibberellins were destroyed by Daminozide, lack of Daminozide effects on SVglys production suggests that gibberellins biosynthesis could not act as a competitive factor for SVglys production in Stevia leaves.

Aim: To assess and compare the image quality of 4% sorbitol and diluted iodine 2% (positive oral contrast agent) in abdomino-pelvic multi-detector computed tomography., Methods: Two-hundred patients, referred to the Radiology Department of a central educational hospital for multi-detector row abdominal-pelvic computed tomography, were randomly divided into two groups: the first group received 1500 mL of 4% sorbitol solution as a neutral contrast agent, while in the second group 1500 mL of meglumin solution as a positive contrast agent was administered in a one-way randomized prospective study. The results were independently reviewed by two radiologists. Luminal distension and mural thickness and mucosal enhancement were compared between the two groups. Statistical analysis of the results was performed by Statistical Package for the Social Sciences software version 16 and the Mann-Whitney test at a confidence level of 95%., Results: Use of neutral oral contrast agent significantly improved visualization of the small bowel wall thickness and mural appearance in comparison with administration of positive contrast agent (P < 0.01). In patients who received sorbitol, the small bowel showed better distention compared with those who received iodine solution as a positive contrast agent (P < 0.05)., Conclusion: The results of the study demonstrated that oral administration of sorbitol solution allows better luminal distention and visualization of mural features than iodine solution as a positive contrast agent.

Background: Increasing antibiotic resistance of Helicobacter pylori (H. pylori) which is associated with diseases of the upper gastrointestinal tract, has made alternative treatments necessary. This study compares the efficacy of adding N-acetyl cysteine (NAC) to standard regimen for H. pylori eradication., Materials and Methods: We conducted a randomized, open-label trial, comparing the efficacy of 14 days of quadruple therapy with Amoxicillin, Bismuth citrate, Omeprazole, Clarithromycin (group A) versus 14 days of above regimen plus NAC (group B) in adult patients with dyspepsia. Primary objective was H. pylori eradication. Compliance and side effects were determined by questionnaires. Our analysis was by intention-to-treat (ITT) and per-protocol. This study is registered with www.IRCT.ir, number: IRCT201201078634N1., Result: A total of 121 participants aged 21-76 years with a mean age of 44.5 ± 14.1, and 52.9% female, were randomly allocated a treatment: 60 with 14-day standard therapy and 61 with 14-day standard therapy with NAC. The eradication rate in groups A and B with ITT analyses was 49/60 (81.7%; 95% [confidence intervals] CI = 71.6-91.8%) and 50/61 (82%; 95% CI = 72-91.9%), respectively (P = 0.96). In per-protocol analysis, the rate of H. pylori eradication in groups A and B was 45/54 (83.3%; 95% CI = 73.1-93.6%) and 45/53 (84.9%; 95% CI = 74.9-94.9%), respectively (P = 0.82). Minor well tolerated side effects were reported in 15 (34.9%) and 21 (35.6%) patients of groups A and B, respectively, and only one therapy cessation in group A was created., Conclusion: Standard 14-day triple-drug therapy with NAC is not preferable to standard drug regimens for H. pylori infection.

Background: Accurate radiological assessment of the anatomical features of the temporal bone is crucial to prevent damage to vital elements in this area during surgery. Knowing the approximate location of specific temporal bone related landmarks in advance is very important for planning surgery., Objectives: This study compared findings from computed tomography images with those observed directly during ear surgery., Patients and Methods: Patients with various pathologies of the ear who needed surgery were referred to an imaging center for a spiral CT scan of the temporal bone. The following parameters were measured by a radiologist and also later recorded by the surgeon during surgery: 1) The distance between the postero-superior border of the outer ear canal and the sigmoid sinus; 2) The distance between the dome of the lateral semicircular canal and the mastoid cortex; and 3) The distance between the external surface of the incus and the mastoid cortex., Results: Twenty cases were included. In the three measurements performed in this study, only the first parameter (distance between the canal and the sigmoid sinus) was significantly different between the direct measurement made during surgery and that obtained from CT scans. There was no significant difference in the measurements of the distance between the dome of the lateral semicircular canal and the bone cortex, and the distance between the external surface of the incus and the surface of the bone cortex., Conclusions: Our study shows in terms of figures that measurements of features of the temporal bone made from spiral CT scan images and those directly obtained during surgery are similar to an adequate extent.

Background: The morphometric characteristics of the anterior cruciate ligament (ACL) and the femoral intercondylar notch within which it resides have been implicated as risk factors for injuries to this important stabilizer of the knee. Prior research has produced equivocal results with differing methodologies, and consequently, it is unclear how these characteristics affect the injury risk in male and female patients., Hypothesis: The morphometric characteristics of the ACL and femoral intercondylar notch are individually and independently associated with the risk of suffering a noncontact ACL injury, and these relationships are different in male and female patients., Study Design: Case-control study; Level of evidence, 3., Methods: Magnetic resonance imaging scans of the bilateral knees were obtained on 88 case-control pairs (27 male, 61 female) matched for age, sex, and participation on the same sports team. Patients had suffered a grade III, first-time, noncontact ACL tear. The femoral notch width at 4 locations, the thickness of the bony ridge at the anteromedial outlet of the femoral notch, the femoral notch volume, ACL volume, and ACL cross-sectional area were measured., Results: Multivariate analysis of combined data from male and female patients revealed that decreased ACL volume (odds ratio [OR], 0.829), decreased femoral notch width (OR, 0.700), and increased bony ridge thickness at the anteromedial outlet of the femoral notch (OR, 1.614) were significant independent predictors of an ACL injury. Separate analyses of male and female patients indicated that the femoral notch ridge may be more strongly associated with a risk in female patients, while ACL volume is more strongly associated with a risk in male patients. However, statistical analysis performed with an adjustment for body weight strengthened the association between ACL volume and the risk of injuries in female patients., Conclusion: Morphometric features of both the ACL and femoral notch combine to influence the risk of suffering a noncontact ACL injury. When included together in a multivariate model that adjusts for body weight, the effects of the morphometric measurements are similar in male and female patients. If body weight is not taken into consideration, ACL volume is not associated with a risk in female patients., (© 2014 The Author(s).)

Aberrant DNA methylation is a feature of human cancer affecting gene expression and tumor phenotype. Here, we quantified promoter methylation of candidate genes and global methylation in 44 small intestinal-neuroendocrine tumors (SI-NETs) from 33 patients by pyrosequencing. Findings were compared with gene expression, patient outcome and known tumor copy number alterations. Promoter methylation was observed for WIF1, RASSF1A, CTNNB1, CXCL14, NKX2-3, P16, LAMA1, and CDH1. By contrast APC, CDH3, HIC1, P14, SMAD2, and SMAD4 only had low levels of methylation. WIF1 methylation was significantly increased (P = 0.001) and WIF1 expression was reduced in SI-NETs vs. normal references (P = 0.003). WIF1, NKX2-3, and CXCL14 expression was reduced in metastases vs. primary tumors (P<0.02). Low expression of RASSF1A and P16 were associated with poor overall survival (P = 0.045 and P = 0.011, respectively). Global methylation determined by pyrosequencing of LINE1 repeats was reduced in tumors vs. normal references, and was associated with loss in chromosome 18. The tumors fell into three clusters with enrichment of WIF1 methylation and LINE1 hypomethylation in Cluster I and RASSF1A and CTNNB1 methylation and loss in 16q in Cluster II. In Cluster III, these alterations were low-abundant and NKX2-3 methylation was low. Similar analyses in the SI-NET cell lines HC45 and CNDT2 showed methylation for CDH1 and WIF1 and/or P16, CXCL14, NKX2-3, LAMA1, and CTNNB1. Treatment with the demethylating agent 5-azacytidine reduced DNA methylation and increased expression of these genes in vitro. In conclusion, promoter methylation of tumor suppressor genes is associated with suppressed gene expression and DNA copy number alterations in SI-NETs, and may be restored in vitro.

Candida albicans, the most prevalent human fungal pathogen, is generally diploid. However, 50% of isolates that are resistant to fluconazole (FLC), the most widely used antifungal, are aneuploid and some aneuploidies can confer FLC resistance. To ask if FLC exposure causes or only selects for aneuploidy, we analyzed diploid strains during exposure to FLC using flow cytometry and epifluorescence microscopy. FLC exposure caused a consistent deviation from normal cell cycle regulation: nuclear and spindle cycles initiated prior to bud emergence, leading to "trimeras," three connected cells composed of a mother, daughter, and granddaughter bud. Initially binucleate, trimeras underwent coordinated nuclear division yielding four daughter nuclei, two of which underwent mitotic collapse to form a tetraploid cell with extra spindle components. In subsequent cell cycles, the abnormal number of spindles resulted in unequal DNA segregation and viable aneuploid progeny. The process of aneuploid formation in C. albicans is highly reminiscent of early stages in human tumorigenesis in that aneuploidy arises through a tetraploid intermediate and subsequent unequal DNA segregation driven by multiple spindles coupled with a subsequent selective advantage conferred by at least some aneuploidies during growth under stress. Finally, trimera formation was detected in response to other azole antifungals, in related Candida species, and in an in vivo model for Candida infection, suggesting that aneuploids arise due to azole treatment of several pathogenic yeasts and that this can occur during the infection process., Competing Interests: The authors have declared that no competing interests exist.

The early detection of developmental disorders is key to child outcome, allowing interventions to be initiated which promote development and improve prognosis. Research on autism spectrum disorder (ASD) suggests that behavioral signs can be observed late in the first year of life. Many of these studies involve extensive frame-by-frame video observation and analysis of a child's natural behavior. Although nonintrusive, these methods are extremely time-intensive and require a high level of observer training; thus, they are burdensome for clinical and large population research purposes. This work is a first milestone in a long-term project on non-invasive early observation of children in order to aid in risk detection and research of neurodevelopmental disorders. We focus on providing low-cost computer vision tools to measure and identify ASD behavioral signs based on components of the Autism Observation Scale for Infants (AOSI). In particular, we develop algorithms to measure responses to general ASD risk assessment tasks and activities outlined by the AOSI which assess visual attention by tracking facial features. We show results, including comparisons with expert and nonexpert clinicians, which demonstrate that the proposed computer vision tools can capture critical behavioral observations and potentially augment the clinician's behavioral observations obtained from real in-clinic assessments.

Background: Small intestinal neuroendocrine tumors (SI-NETs) are typically slow-growing tumors that have metastasized already at the time of diagnosis. The purpose of the present study was to further refine and define regions of recurrent copy number (CN) alterations (CNA) in SI-NETs., Methods: Genome-wide CNAs was determined by applying array CGH (a-CGH) on SI-NETs including 18 primary tumors and 12 metastases. Quantitative PCR analysis (qPCR) was used to confirm CNAs detected by a-CGH as well as to detect CNAs in an extended panel of SI-NETs. Unsupervised hierarchical clustering was used to detect tumor groups with similar patterns of chromosomal alterations based on recurrent regions of CN loss or gain. The log rank test was used to calculate overall survival. Mann-Whitney U test or Fisher's exact test were used to evaluate associations between tumor groups and recurrent CNAs or clinical parameters., Results: The most frequent abnormality was loss of chromosome 18 observed in 70% of the cases. CN losses were also frequently found of chromosomes 11 (23%), 16 (20%), and 9 (20%), with regions of recurrent CN loss identified in 11q23.1-qter, 16q12.2-qter, 9pter-p13.2 and 9p13.1-11.2. Gains were most frequently detected in chromosomes 14 (43%), 20 (37%), 4 (27%), and 5 (23%) with recurrent regions of CN gain located to 14q11.2, 14q32.2-32.31, 20pter-p11.21, 20q11.1-11.21, 20q12-qter, 4 and 5. qPCR analysis confirmed most CNAs detected by a-CGH as well as revealed CNAs in an extended panel of SI-NETs. Unsupervised hierarchical clustering of recurrent regions of CNAs revealed two separate tumor groups and 5 chromosomal clusters. Loss of chromosomes 18, 16 and 11 and gain of chromosome 20 were found in both tumor groups. Tumor group II was enriched for alterations in chromosome cluster-d, including gain of chromosomes 4, 5, 7, 14 and gain of 20 in chromosome cluster-b. Gain in 20pter-p11.21 was associated with short survival. Statistically significant differences were observed between primary tumors and metastases for loss of 16q and gain of 7., Conclusion: Our results revealed recurrent CNAs in several candidate regions with a potential role in SI-NET development. Distinct genetic alterations and pathways are involved in tumorigenesis of SI-NETs.

Objective: To study long-term subjective benefit of patients with sensorineural hearing loss and chronic external otitis who use active middle ear implants., Design: Single-subject repeated measures in a preintervention and postintervention design with multiple postintervention measurements (questionnaires)., Setting: Tertiary academic center., Patients: Moderate-to-severe sensorineural hearing loss (n = 56) with severe chronic external otitis who use the Vibrant Soundbridge (VSB) or Otologics MET middle ear implant systems., Main Outcome Measure: Changes in hearing disability and handicap as evaluated using the Abbreviated Profile of Hearing Aid Benefit (APHAB), the Nijmegen Cochlear Implant Questionnaire (NCIQ), and the Glasgow Benefit Inventory (GBI)., Results: Data of 33 patients (mean postoperative duration of 7.5 yr) were available. No difference in subjective results was found between the VSB and Otologics MET patient groups. Total percentage of nonuse was 13%. Long-term APHAB results show a significant decrease in disability for 43% of the patients compared with 54% at 1-year postoperative. NCIQ results show a significant benefit for all subdomains with a negative trend over time. The GBI results show a significant long-term increase in quality of life with positive scores for 82% of the assessed patients., Conclusion: Long-term postoperative patient satisfaction and quality of life results show a significant difference compared with preoperative measurements, with conventional hearing aids. A negative trend over time is found on all questionnaires, which might reflect patient aging (increase of hearing loss) or habituation to a situation with fewer concerns regarding a patient's external otitis.

Epigenetic mechanisms involved in primary hyperparathyroidism are poorly understood as studies are limited. In order to understand the role of aberrant DNA promoter methylation in the pathogenesis of parathyroid tumors, we have quantified the CpG island promoter methylation density of several candidate genes including APC (promoter 1A and 1B), β-catenin (CTNNB1), CASR, CDC73/HRPT2, MEN1, P16 (CDKN2A), PAX1, RASSF1A, SFRP1 and VDR in 72 parathyroid tumors and 3 normal parathyroid references using bisulfite pyrosequencing. Global methylation levels were assessed for LINE-1. We also compared methylation levels with gene expression levels measured by qRT-PCR for genes showing frequent hypermethylation. The adenomas displayed frequent hypermethylation of APC 1A (37/66; 56%), RASSF1A (34/66; 52%) and β-catenin (19/66; 29%). One of the three atypical adenomas was hypermethylated for APC 1A. The three carcinomas were hypermethylated for RASSF1A and SFRP1, and the latter was only observed in this subtype. The global methylation density was similar in tumors (mean 70%) and parathyroid reference samples (mean 70%). In general, hypermethylated genes had reduced expression in the parathyroid adenomas using qRT-PCR. Among the adenomas, methylation of APC 1A correlated with adenoma weight (r = 0.306, p < 0.05). Furthermore, the methylation status of RASSF1A correlated with each of APC 1A (r = 0.289, p < 0.05) and β-catenin (r = 0.315, p < 0.01). Our findings suggest a role for aberrant DNA promoter methylation of APC 1A, β-catenin and RASSF1A in a subset of parathyroid tumors.

In this paper, a calibration method to compensate for changes in SEMG amplitude with joint angle is introduced. Calibration factors were derived from constant amplitude surface electromyogram (SEMG) recordings from the biceps brachii (during elbow flexion) and the triceps brachii (during elbow extension) across seven elbow joint angles. SEMG data were then recorded from the elbow flexors (biceps brachii and brachioradialis) and extensors (triceps brachii) during isometric, constant force flexion and extension contractions at the same joint angles. The resulting force at the wrist was measured. The fast orthogonal search method was used to find a mapping between the system inputs - estimated SEMG amplitudes and joint angle - and the system output - measured force, for both calibrated and non-calibrated SEMG data. Models developed with calibrated data yielded a statistically significant improvement in force estimation compared to models developed with non-calibrated data, suggesting that the calibration method can compensate for changes in the SEMG-force relationship with changing joint angle. It was also found that the number of non-linear, joint angle-dependent terms used in the SEMG-force model was reduced with calibration. Additionally, initial inter-session analysis performed for four subjects suggests that calibration values can be used for subsequent recording sessions, and different output force levels., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Acute pancreatitis is the most common serious complication of endoscopic retrograde cholangiopancreatography (ERCP) that can occasionally be fatal. Multiple drugs have been examined for the prevention of this side effect, with generally uncertain results. This study is an effort to prevent this complication by the use of oral N-acetyl cysteine (NAC)., Methods: A total of 100 patients who were candidates for ERCP were divided randomly into two groups. In the NAC (N) group, patients received 1200 mg NAC with 150 cc water orally 2 h before ERCP. In the placebo (P) group, 150 cc water was prescribed as a placebo. We measured serum amylase and lipase levels before and 24 h after ERCP. The prevalence of pancreatitis and duration of admission in each group were determined and compared., Results: In group N there were 5 (10%) cases of pancreatitis, whereas in group P there were 14 (28%) cases, which was significant (risk reduction ratio: 2.8; p=0.02).The average admission time was 1.16±0.55 days in group N and 1.18±0.44 days in group P, which was not significant., Conclusion: There were significant differences in the prevalence of acute pancreatitis between the two groups. In addition, the number of need to treat (NNT) consisted of five cases for NAC. With regards to the above results and the safety profile of NAC, it could be used as a therapeutic agent for the prevention of post-ERCP pancreatitis. We recommend that the results of this study be verified by additional clinical trials.

Background: Cardiovascular operations are associated with an inherent bleeding tendency that sometimes leads to severe bleeding and transfusion requirement. Pharmacological intervention to minimize post-bypass bleeding and blood product transfusions has received increasing attention from both medical and economic viewpoints., Methods: This double-blind, randomized, placebo-controlled clinical trial recruited three groups of patients (each group consisting of 50 patients) undergoing on-pump coronary artery bypass graft surgery (CABG) and blindly randomized them to receive either low aprotinin, tranexamic acid, or placebo. The results were, subsequently, evaluated and compared between the groups. All the patients were operated on by one surgeon and the same surgery team., Results: THE FOLLOWING VARIABLES WERE SIMILAR BETWEEN THE GROUPS, AND THERE WAS NO STATISTICALLY SIGNIFICANT DIFFERENCE BETWEEN THE GROUPS IN TERMS OF THESE VARIABLES: age (p value = 0.308), sex (p value = 0.973), hyperlipidemia (p value = 0.720), hypertension (p value = 0.786), smoking (p value = 0.72), and diabetes (p value = 0.960). The amounts of drainage from chest tubes were less in the aprotinin and tranexamic acid groups than the amount in the placebo group; the difference was statistically important (p value < 0.001). There was no statistically significant difference with respect to need for reoperation for bleeding between the three groups (p value = 0.998). Complications following surgery in the three groups were statistically the same and not significantly different. All the complications (myocardial infarction, pericardial effusion, neurological complication and renal complication) had a good course, and all the patients were discharged from the hospital uneventfully. There was no mortality in any group., Conclusion: Low-dose aprotinin and tranexamic acid can significantly reduce blood loss and transfusion requirement in CABG without importantly increasing mortality and morbidity.

In this study, we genetically characterized parathyroid adenomas with large glandular weights, for which independent observations suggest pronounced clinical manifestations. Large parathyroid adenomas (LPTAs) were defined as the 5% largest sporadic parathyroid adenomas identified among the 590 cases operated in our institution during 2005-2009. The LPTA group showed a higher relative number of male cases and significantly higher levels of total plasma and ionized serum calcium (P<0.001). Further analysis of 21 LPTAs revealed low MIB1 proliferation index (0.1-1.5%), MEN1 mutations in five cases, and one HRPT2 (CDC73) mutation. Total or partial loss of parafibromin expression was observed in ten tumors, two of which also showed loss of APC expression. Using array CGH, we demonstrated recurrent copy number alterations most frequently involving loss in 1p (29%), gain in 5 (38%), and loss in 11q (33%). Totally, 21 minimal overlapping regions were defined for losses in 1p, 7q, 9p, 11, and 15q and gains in 3q, 5, 7p, 8p, 16q, 17p, and 19q. In addition, 12 tumors showed gross alterations of entire or almost entire chromosomes most frequently gain of 5 and loss of chromosome 11. While gain of 5 was the most frequent alteration observed in LPTAs, it was only detected in a small proportion (4/58 cases, 7%) of parathyroid adenomas. A significant positive correlation was observed between parathyroid hormone level and total copy number gain (r=0.48, P=0.031). These results support that LPTAs represent a group of patients with pronounced parathyroid hyperfunction and associated with specific genomic features.

Context: Injuries to the anterior cruciate ligament (ACL) are immediately disabling and are associated with long-term consequences, such as posttraumatic osteoarthritis. It is important to have a comprehensive understanding of all possible risk factors for ACL injury to identify individuals who are at risk for future injuries and to provide an appropriate level of counseling and programs for prevention., Objective: This review, part 2 of a 2-part series, highlights what is known and still unknown regarding hormonal, genetic, cognitive function, previous injury, and extrinsic risk factors for ACL injury., Data Sources: Studies were identified from MEDLINE (1951-March 2011) using the MeSH terms anterior cruciate ligament, knee injury, and risk factors. The bibliographies of relevant articles and reviews were cross-referenced to complete the search., Study Selection: Prognostic case-control and prospective cohort study designs to evaluate risk factors for ACL injury were included in this review., Results: A total of 50 case-control and prospective cohort articles were included in parts 1 and 2. Twenty-one focused on hormonal, genetic, cognitive function, previous injury, and extrinsic risk factors., Conclusions: Several risk factors are associated with increased risk of suffering ACL injury-such as female sex, prior reconstruction of the ACL, and familial predisposition. These risk factors most likely act in combination with the anatomic factors reviewed in part 1 of this series to influence the risk of suffering ACL injury.

Bone-patellar tendon-bone (BPTB) graft is a popular choice for ACL reconstruction. These grafts are subjected to cyclic loading during the activities of daily living. Significant knee laxity is observed in reconstructed knee shortly after reconstruction. The source of this laxity is not clear. The change in the tensile properties of the graft due to cyclic loading can be one of the reasons for the change in knee laxity. Twenty patellar tendons from fresh frozen cadaver knees were cyclically loaded at a stress amplitude equivalent to 33% of the failure strength of the contralateral patellar tendon for 5000 cycles at 1.4Hz. They were then tested in tension to failure. Failure properties and the low load properties such as toe-region modulus were calculated. The results were compared with those of contralateral patellar tendons that were not subjected to cyclic loading before testing to failure. Fatigue loading did not alter the failure and low load properties with the exception of failure strain which decreased by about 10% (P<.05). Cyclically loaded patellar tendons with higher tissue mass density possess higher strength, modulus of elasticity, toughness, and transition stress (P<.05). The results indicate that there is no significant change in graft properties because of cyclic loading with the above load magnitude. The change in knee laxity observed after reconstruction, hence, is not because of change in graft properties due to moderate cyclic loading. Other factors, such as plastic deformation (yielding) of the graft, might play a role in increased knee laxity after reconstruction., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Mutations in the hyperparathyroidism type 2 (HRPT2/CDC73) gene and alterations in the parafibromin protein have been established in the majority of parathyroid carcinomas and in subsets of parathyroid adenomas. While it is known that CDC73-mutated parathyroid tumors display specific gene expression changes compared to CDC73 wild-type cases, the molecular cytogenetic profile in CDC73-mutated cases compared to unselected adenomas (with an expected very low frequency of CDC73 mutations) remains unknown. For this purpose, nine parathyroid tumors with established CDC73 gene inactivating mutations (three carcinomas, one atypical adenoma and five adenomas) were analyzed for copy number alterations and loss of heterozygosity using array-comparative genomic hybridization (a-CGH) and single nucleotide polymorphism (SNP) microarrays, respectively. Furthermore, CDC73 gene promoter methylation levels were assessed using bisulfite Pyrosequencing. The panel included seven tumors with single mutation and three with double mutations of the CDC73 gene. The carcinomas displayed copy number alterations in agreement with previous studies, whereas the CDC73-mutated adenomas did not display the same pattern of alterations at loci frequently deleted in unselected parathyroid tumors. Furthermore, gross losses of chromosomal material at 1p and 13 were significantly (p = 0.012) associated with parathyroid carcinomas as opposed to adenomas. Quantitative PCR-based copy number loss regarding CDC73 was observed in three adenomas, while all the carcinomas were diploid or showed copy number gain for CDC73 gene. Hypermethylation of the CDC73 gene promoter was not observed. Our data could suggest that CDC73-mutated parathyroid adenomas exhibit a partly unique cytogenetic profile in addition to that of carcinomas and unselected adenomas. Furthermore, CDC73-mutated carcinomas displayed losses at 1p and 13 which are not seen in CDC73-mutated adenomas, making these regions of interest for further studies regarding malignant properties in tumors from CDC73-mutated cases. However, due to the small sample size, validation of the results in a larger cohort is warranted.

A modification method based on integrated contact pressure and surface electromyogram (SEMG) recordings over the biceps brachii muscle is presented. Multi-site sEMGs are modified by pressure signals recorded at the same locations for isometric contractions. The resulting pressure times SEMG signals are significantly more correlated to the force induced at the wrist (FW), yielding SEMG-force models with superior performance in force estimation. A sensor patch, combining six SEMG and six contact pressure sensors was designed and built. SEMG, and contact pressure data over the biceps brachii and induced wrist force data were collected from 5 subjects. Polynomial fitting was used to find a mapping between biceps SEMG and wrist force. Comparison between evaluation values from models trained with modified and non-modified SEMG signals revealed a statistically significant superiority of models trained with the modified SEMG.

Background: The benefit of prophylactic combination therapy using crystalloid and colloid preload with ephedrine has not been cleared to prevent maternal hypotension after spinal anesthesia at cesarean delivery. This study evaluated the efficacy of three combinational methods to prevent hypotension following spinal anesthesia., Materials and Methods: In this prospective double blind trial, 150 candidates of elective cesarean delivery under spinal anesthesia were randomly allocated to three treatment groups; 1---Ringer's Lactate (RL) solution (15 ml/kg) plus Hemaxel (7 ml/kg) preload, 2---RL solution (15 ml/kg) preload plus ephedrine (15 mg, IV, bolus), 3---Hemaxel (7 ml/kg) preload plus ephedrine (15 mg, IV, bolus). Maternal hemodynamic changes during 60 min after spinal injection, nausea/vomiting, and neonatal condition were compared among the groups., Results: The cumulative incidence of hypotension was 44%, 40%, and 46% in groups 1 to 3, respectively. There were not significant differences in supplementary ephedrine requirement among groups which received or among groups which did not receive prophylactic ephedrine. Groups were not different in the incidence of hypertension and nausea or vomiting. There were no significant differences among groups in Apgar scores at 1 or 5 min and umbilical artery PH., Conclusion: Combination of preventive methods decreased the occurrence of hypotension following spinal anesthesia to an acceptable level. Overall, the most effective method was a combination of crystalloid preload with ephedrine.

Context: Injuries to the anterior cruciate ligament (ACL) of the knee are immediately debilitating and can cause long-term consequences, including the early onset of osteoarthritis. It is important to have a comprehensive understanding of all possible risk factors for ACL injury to identify individuals who are at risk for future injuries and to provide an appropriate level of counseling and programs for prevention., Objective: This review, part 1 of a 2-part series, highlights what is known and still unknown regarding anatomic and neuromuscular risk factors for injury to the ACL from the current peer-reviewed literature., Data Sources: Studies were identified from MEDLINE (1951-March 2011) using the MeSH terms anterior cruciate ligament, knee injury, and risk factors. The bibliographies of relevant articles and reviews were cross-referenced to complete the search., Study Selection: Prognostic studies that utilized the case-control and prospective cohort study designs to evaluate risk factors for ACL injury were included in this review., Results: A total of 50 case-control and prospective cohort articles were included in the review, and 30 of these studies focused on neuromuscular and anatomic risk factors., Conclusions: Several anatomic and neuromuscular risk factors are associated with increased risk of suffering ACL injury-such as female sex and specific measures of bony geometry of the knee joint, including decreased intercondylar femoral notch size, decreased depth of concavity of the medial tibial plateau, increased slope of the tibial plateaus, and increased anterior-posterior knee laxity. These risk factors most likely act in combination to influence the risk of ACL injury; however, multivariate risk models that consider all the aforementioned risk factors in combination have not been established to explore this interaction.

Background: Various methods have been applied to prevent maternal hypotension after spinal anesthesia for cesarean delivery. We compared the efficacy of three combinational methods in this regard in the current study., Methods: In this randomized comparative trial, 150 candidates of elective cesarean delivery under spinal anesthesia were assigned to three groups: crystalloid preload and leg bandage, colloid preload and leg bandage, and ephedrine and leg bandage. Maternal hemodynamic changes during 60 minutes after spinal injection and neonatal condition were compared among the groups., Results: The cumulative incidence of hypotension was 54%, 64%, and 36% in groups 1 to 3, respectively (p = 0.018). Spinal injection to hypotension interval was similar among the groups (p = 0.828). Heart rate in group 3 was significantly lower at the most time measures after anesthesia compared with the other two groups (p < 0.05 to <0.001). Regarding neonatal outcomes, the interval between the birth and the first breath was longer and the Apgar score at minute 1 was lower in group 3 compared with the other groups (p < 0.001 and 0.038, respectively) but it was not clinically important. Umbilical cord blood pH was similar among the three groups (p = 0.248)., Conclusions: Among the three studied methods, administration of ephedrine plus bandage of the lower extremities was the most effective one in reducing the incidence of post-spinal hypotension. The groups were not clinically different concerning the effect of treatment on newborn health.

Exposure of MOLT4 human T-cell leukemia cells to 6-Mercaptopurine (6-MP) and 6-Thioguanine (6-TG) resulted in acquired resistance associated with attenuated expression of the genes encoding concentrative nucleoside transporter 3 (CNT3) and equilibrative nucleoside transporter 2 (ENT2). To identify other alterations at the RNA and DNA levels associated with 6-MP- and 6-TG resistance, we compared here the patterns of gene expression and DNA copy number profiles of resistant sublines to those of the parental wild-type cells. The mRNA levels for two nucleoside transporters were down-regulated in both of the thiopurine-resistant sublines. Moreover, both of these cell lines expressed genes encoding the enzymes of purine nucleotide composition and synthesis, including adenylate kinase 3-like 1 and guanosine monophosphate synthetase at significantly lower levels than wild-type cells. In addition, expression of the mRNA for a specialized DNA polymerase, human terminal transferase encoded by the terminal deoxynucleotidyl transferase (DNTT) gene, was 122- and 93-fold higher in 6-TG- and 6-MP-resistant cells, respectively. The varying responses to 6-MP- and 6-TG observed here may help identify novel cellular targets and modalities of resistance to thiopurines, as well as indicating new potential approaches to individualization therapy with these drugs., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Anterior cruciate ligament (ACL) injury continues to be at the forefront of sports injury concerns because of its impact on quality of life and joint health prognosis. One strategy is to reduce the occurrence of this injury by identifying at-risk subjects based on key putative risk factors. The purpose of our study was to develop models that predict the structural properties of a subject's ACL based on the combination of known risk factors. We hypothesized that the structural properties of the ACL can be predicted using a multi-linear regression model based on significant covariates that are associated with increased risk of injury, including age, sex, body size, and ACL size. We also hypothesized that ACL size is a significant contributor to the model. The developed models had predictive capabilities for the structural properties of the ACL: load at failure (R2 = 0.914), elongation at failure (R2 = 0.872), energy at failure (R2 = 0.913), and linear stiffness (R2 = 0.756). Furthermore, sex, age, body mass, BMI, and height were contributors (p < 0.05) to all predicted structural properties. ACL minimal area was a contributor to elongation, energy at failure, and linear stiffness (p < 0.05), but not to load at failure. ACL volume was also a contributor to elongation and energy at failure (p < 0.05), but not to linear stiffness and load at failure models. ACL length was not a significant contributor to any structural property. The clinical significance of this research is its potential, after continued development and refinement of the model, for application to prognostic studies that are designed to identify individuals at increased risk for injury to the ligament., (Copyright © 2011 Orthopaedic Research Society.)

Anterior cruciate ligament (ACL) rupture is a common and traumatic injury. Although, identifying the mechanism of ACL injury has received considerable research attention, there are still many unanswered questions. One proposed mechanism asserts that the ACL is injured due to an aggressive quadriceps muscle contraction. However, recently it has been questioned if the magnitude of quadriceps force needed to tear the ACL is physiologically realistic under the conditions where injury occurs during landing (e.g. near full knee extension and within 50ms after impact). To answer this question, a simple simulation model was developed to examine the upper bounds of quadriceps force that can be developed under these conditions. The model included force-length, and force-velocity properties as well as activation dynamics. Model parameters were chosen to provide a high estimate for possible quadriceps force in a young healthy man. The effects of varying quadriceps pre-activation levels were also examined. When using realistic pre-activation levels, the simulated quadriceps force was less than half of what has been shown to cause ACL injury. Even when using maximum pre-activation, the quadriceps force still did not reach close to the level shown to cause injury. Therefore, we conclude that quadriceps force alone seems to be an unlikely mechanism for ACL injury., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

A total of 55 consecutive patients who experienced perioperative myocardial infarction (MI) after coronary artery bypass grafting were studied using multislice computed tomography (MSCT) angiography to evaluate for graft patency. The MSCT detected acute graft occlusion in 23% grafts. Of the 55 patients, 40% patients had occluded grafts and perioperative MI in the area of the grafted vessels; remaining 60% had patent grafts with infarction in the area of the grafted vessels. Compared with the patients with patent grafts, those with occluded grafts had a higher blood sugar level. In addition, graft occlusion was higher in grafts with severe distal disease. Among the patients with patent grafts, luminal stenosis of the native vessels supplying the infarcted myocardium was higher than that in the native vessels supplying the non-infarcted myocardium. In conclusion, MSCT is feasible for the assessment of graft patency in the setting of perioperative MI. Graft occlusion is detected in less than half of the cases and usually occurs in the grafts with severe distal involvement and the patients with uncontrolled hyperglycemia. In patients with patent grafts, the severity of luminal stenosis of the native grafted vessel is the main predisposing factor for perioperative MI.

Background: Picropodophyllin (PPP) is a promising novel anti-neoplastic agent that efficiently kills tumor cells in vitro and causes tumor regression and increased survival in vivo. We have previously reported that PPP treatment induced moderate tolerance in two out of 10 cell lines only, and here report the acquired genomic and expression alterations associated with PPP selection over 1.5 years of treatment., Methodology/principal Findings: Copy number alterations monitored using metaphase and array-based comparative genomic hybridization analyses revealed largely overlapping alterations in parental and maximally tolerant cells. Gain/amplification of the MYC and PVT1 loci in 8q24.21 were verified on the chromosome level. Abnormalities observed in connection to PPP treatment included regular gains and losses, as well as homozygous losses in 10q24.1-q24.2 and 12p12.3-p13.2 in one of the lines and amplification at 5q11.2 in the other. Abnormalities observed in both tolerant derivatives include amplification/gain of 5q11.2, gain of 11q12.1-q14.3 and gain of 13q33.3-qter. Using Nexus software analysis we combined the array-CGH data with data from gene expression profilings and identified genes that were altered in both inputs. A subset of genes identified as downregulated (ALDH1A3, ANXA1, TLR4 and RAB5A) or upregulated (COX6A1, NFIX, ME1, MAPK and TAP2) were validated by siRNA in the tolerant or parental cells to alter sensitivity to PPP and confirmed to alter sensitivity to PPP in further cell lines., Conclusions: Long-term PPP selection lead to altered gene expression in PPP tolerant cells with increase as well as decrease of genes involved in cell death such as PTEN and BCL2. In addition, acquired genomic copy number alterations were observed that were often reflected by altered mRNA expression levels for genes in the same regions.

Background: Increase in intraocular pressure (IOP) following tracheal intubation during general anesthesia can be troublesome. We compared the influence of two muscle relaxants, cisatracurium and atracurium, on IOP in patients undergoing general anesthesia., Methods: This randomized, double-blind, comparative trial was conducted on 90 candidates for elective non-ophthalmic surgery under general anesthesia. Patients were 18 to 60 years old with the American Society of Anesthesiologists (ASA) class of I or II. Anesthesia was induced with fentanyl (1.5 mg/kg) and sodium thiopental (5 mg/kg). Patients received atracurium (0.5 mg/kg) or cisatracurium (0.15 mg/kg) two minutes prior to tracheal intubation. IOP, systolic (SBP) and diastolic blood pressure (DBP), and heart rate (HR) were measured at baseline (before medication), after medication (before intubation), and 2, 5, and 10 minutes after intubation., Results: In both groups IOP decreased after administration of muscle relaxants (-3.3 ± 3.6 mmHg), then increased 2 minutes after intubation (5.5 ± 4.4 mmHg), but decreased 5 (-3.3 ± 3.3 mmHg) and 10 (-0.5 ± 2.6 mmHg) minutes after intubation. IOP and SBP were significantly higher in the atracurium compared with the cisatracurium group after 2 (p < 0.001 and 0.002, respectively), 5 (p < 0.001 and 0.012, respectively), and 10 (p = 0.02 and 0.048, respectively) minutes after intubation., Conclusions: Compared with atracurium, administration of cisatracurium can better prevent the increase of IOP following tracheal intubation in general anesthesia. The observed difference might be related to different effects on hemodynamic variables. Application of these results in patients under ophthalmic surgery is warranted.

Considering that an athlete performs at-risk sports activities countless times throughout the course of his or her career prior to the instance of anterior cruciate ligament (ACL) injury, one may conclude that non-contact ACL injury is a rare event. Nevertheless, the overall number of non-contact ACL injuries, both in the US and worldwide, remains alarming due to the growing number of recreational and professional athletes participating in high-risk activities. To date, numerous non-contact ACL injury mechanisms have been proposed, but none provides a detailed picture of sequence of events leading to injury and the exact cause of this injury remains elusive. In this perspective article, we propose a new conception of non-contact ACL injury mechanism that comprehensively integrates risk factors inside and outside the knee joint. The proposed mechanism is robust in the sense that it is biomechanically justifiable and addresses a number of confounding issues related to ACL injury., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

A calibration method is proposed to compensate for the changes in the surface electromyogram (SEMG) amplitude level of the biceps brachii at different joint angles due to the movement of the muscle bulk under the EMG electrodes for a constant force level. To this end, an experiment was designed, and SEMG and force measurements were collected from 5 subjects. The fast orthogonal search (FOS) method was used to find a mapping between SEMG from the biceps and force recorded at the wrist. Comparison between evaluation values from models trained with calibrated and non-calibrated SEMG signals revealed a statistically significant superiority of models trained with the calibrated SEMG.

We hypothesize that application of an unopposed quadriceps force coupled with an impulsive ground reaction force may induce anterior cruciate ligament (ACL) injury. This situation is similar to landing from a jump if only the quadriceps muscle is active; an unlikely but presumably dangerous circumstance. The purpose of this study was to test our hypothesis using in vitro simulation of jump landing. A jump-landing simulator was utilized. Nine cadaveric knees were tested at an initial flexion angle of 20 degrees . Each ACL was instrumented with a differential variable reluctance transducer (DVRT). Quadriceps pre-activation forces (QPFs) ranging from 25N to 700N were applied to each knee, followed by an impulsive ground reaction force produced by a carriage-mounted drop weight (7kg) that impulsively drove the ankle upward. ACL strain was monitored before landing due to application of QPF (pre-activation strain) and at landing due to application of the ground reaction force (landing strain). No ACLs were injured. Pre-activation strains exhibited a positive correlation with QPF (r=0.674, p<0.001) while landing strains showed a negative correlation (r=-0.235, p=0.032). Total ACL strain (pre-activation+landing strain) showed no correlation with QPF (r=0.023, p=0.428). Our findings indicate that elevated QPF increases pre-activation strain but reduces the landing strain and is therefore protective post-landing. Overall, there is a complete lack of correlation between "total" ACL strain and QPF suggesting that the total strain in the ACL is independent of the QPF under the simulated conditions.

Background: The geometry of the tibial plateau has been largely ignored as a source of possible risk factors for anterior cruciate ligament injury. Discovering the anterior cruciate ligament injury risk factors associated with the tibial plateau may lead to delineation of the existing sex-based disparity in anterior cruciate ligament injuries and help develop strategies for the prevention of anterior cruciate ligament injuries regardless of gender., Hypothesis: Individuals with a shallower medial tibial depth of concavity, while having increased posteriorly directed slope of their tibial plateau, are at increased risk of suffering an anterior cruciate ligament injury compared with those with decreased posterior slope and increased medial tibial depth. Furthermore, these relationships are different between men and women., Study Design: Case-control study (prevalence); Level of evidence, 3., Methods: The medial, lateral, and coronal tibial plateau slopes as well as the medial tibial depth of concavity in 55 uninjured controls (33 women and 22 men) and 49 anterior cruciate ligament-injured cases (27 women and 22 men) were measured using magnetic resonance images. First, a preliminary t test was performed to establish any existing differences between groups. Next, a logistic regression model was developed to determine the probability of anterior cruciate ligament injury in an individual based on the measured covariates., Results: The female anterior cruciate ligament-injured cases had increased lateral tibial slope (P = .03) and shallower medial tibial depth (P = .0003) compared with the uninjured controls, while male cases had increased lateral and medial tibial slope (P = .02) and shallower medial tibial depth (P = .0004) compared with controls. The logistic regression analysis and odds ratio estimates showed that medial tibial depth is an important risk factor (odds ratio = 3.03 per 1 mm decrease in its value), followed by lateral tibial slope (odds ratio = 1.17 per 1 degrees increase in its value) in all participants. The medial tibial slope (odds ratio = 1.18 per 1 degrees increase in its value) was a risk factor only in men., Conclusion: A combination of increased posterior-directed tibial plateau slope and shallow medial tibial plateau depth could be a major risk factor in anterior cruciate ligament injury susceptibility regardless of gender. Different injury risk models may be needed for men and women as other key risk factors are identified.

Parallel cascade identification (PCI) is used as a dynamic estimation tool to map surface electromyography recordings from upper-arm muscles to the elbow-induced force at the wrist. PCI mapping is composed of parallel connection of a cascade of linear dynamic and nonlinear static blocks. Experimental comparison between PCI and previously published orthogonalization scheme has shown superior force prediction by PCI. The improved performance is attributed to the structural capability of PCI in capturing nonlinear dynamic effects in the generated force.

Fluorescence properties of ochratoxin A (OTA) solutions depend on the pH, solvent polarity and can be influenced by the presence of cyclodextrins (CDs). In this work, the effect of b-cyclodextrin (b-CD) and heptakis-2,6-dimethyl-o-b-cyclodextrin (ome-CD), on fluorescence properties of OTA in aqueous solutions has been investigated by means of steady-state fluorescence at different pHs (range 2-10). Binding constants of OTA/CDs inclusion complexes have been determined by applying by non-linear regression analysis. A 1:1 stoichiometry of OTA/CDs complexes has been observed at all tested pHs. The use of ome-CD generally resulted in the greatest fluorescence intensity. The effects of solvent and pH on the positions of lambdamax (excitation) and lambdamax (emission) of OTA was determined. Correlations between the excitation and emission wavelength of OTA (monoanion and dianionic forms) and the solvent parameters were analysed with Lippert-Mataga plots. Results show that the peak position is affected mainly by specific and non-specific types of interactions between the solvent and solute. The fluorescence quenching of OTA by chloroform (aprotic) and water (protic) were studied in methanol as solvent at room temperature. The quenching was found to be appreciable and a non-linear curve with downward curvature was obtained in the Stern-Volmer (SV) plot for the water in the concentration range studied. The quenching efficiency is related to hydrogen bond-donating capacity of the quencher molecule. It was inferred that non-linearity can be attributed to fractional accessibility of fluorophore to quencher. The quenching constant was calculated from the modified SV equation.

In vitro treatment of human T-cell leukemia cells with 7-hydroxymethotrexate, the major metabolite of methotrexate resulted in acquired resistance as a result of the complete loss of folypolyglutamate synthetase (FPGS) activity. This was in contradistinction to the major modality of antifolate resistance of impaired drug transport in leukemia cells exposed to methotrexate. To identify the genes associated with methotrexate and 7-hydroxymethotrexate resistance, we herein explored the patterns of genome-wide expression profiles in these antifolte-resistant leukemia sublines. mRNA levels of the reduced folate carrier, the primary influx transporter of folates and antifolates, were down-regulated more than two-fold in methotrexate-resistant cells. The dramatic loss of FPGS activity in 7-hydroxymethotrexate-resistant cells was associated with alterations in the expression of various genes aimed at preserving reduced folates and/or enhancing purine nucleotide biosynthesis, e.g. methylene tetrahydrofolate reductase, glycinamide ribonucleotide formyltransferase, adenosine deaminase, cystathionine beta synthase, as well as the ATP-dependent folate exporters BCRP/ABCG2 and MRP1/ABCC1. The observed changes in gene expression were generally not paralleled by acquired DNA copy numbers alterations, suggesting transcriptional regulatory mechanisms. Interestingly, gene expression of DNA/RNA metabolism and transport genes were more profoundly altered in methotrexate-resistant subline, whereas in 7-hydroxymethotrexate-resistant cells, the most profoundly affected groups of genes were those encoding for proteins involved in metabolism and cellular proliferation. Thus, the present investigation provides evidence that 7-hydroxymethotrexate induces gene expression alterations and an antifolate resistance modality that are distinct from its parent drug methotrexate.

Background: Many microorganisms in midgut of mosquito challenge with their host and also other pathogens present in midgut. The aim of this study was presence of non-pathogens microorganisms like fungal flora which may be crucial on interaction between vectors and pathogens., Methods: Different populations of Anopheles stephensi were reared in insectary and objected to determine fungal flora in their midguts. The midgut paunch of mosquito adults and larvae as well as breading water and larval food samples transferred on Subaru-dextrose agar, in order to detect the environment fungus., Results: Although four fungi, Aspergillus, Rhizopus, Geotrichum and Sacharomyces were found in the food and water, but only Aspiragilus observed in the midgut of larvae. No fungus was found in the midgut of adults. This is the first report on fungal flora in the midgut of the adults and larvae of An. stephensi and possible stadial transmission of fungi from immature stages to adults., Conclusion: The midgut environment of adults is not compatible for survivorship of fungi but the larval midgut may contain few fungi as a host or even pathogen.

Aim: To determine the prevalence of celiac disease (CD) in children with idiopathic short stature (ISS) and the diagnostic value of immunoglobulin (Ig) A G antigliadin antibodies (AGA) and transglutaminase (TTG) antibodies for CD., Methods: A total of 104 children (49 male, 55 female) with ISS without a specific etiology were studied. Extensive endocrine investigations had shown no abnormalities in any subject. Anthropometric parameters and IgA AGA and IgA TTG antibodies were evaluated in this study group. These antibodies were measured by enzyme-linked immunosorbent assay. All patients were referred for an endoscopic intestinal biopsy. The biopsy samples were classified according to revised Marsh criteria (UEGW 2001)., Results: We detected positive IgA TTG antibodies in 36 and IgA AGA in 35 of these patients. Thirty one IgA TTG antibody positive and 28 IgA AGA positive subjects showed histological abnormalities compatible with celiac disease (33.6%). Sensitivity, specificity, positive predictive value (PPV) and negative predictive value for IgA AGA were found to be 80%, 88.4%, 77.8% and 89.7%, respectively. Sensitivity, specificity and PPV for IgA TTG antibodies were 88.6%, 94.2% and 88.6%, respectively., Conclusion: We conclude that the prevalence of celiac disease is high in patients with ISS and it is important to test all children with ISS for celiac disease by measuring serologic markers and performing an intestinal biopsy.

Background: The geometry of the tibial plateau is complex and asymmetric. Previous research has characterized subject-to-subject differences in the tibial plateau geometry in the sagittal plane on the basis of a single parameter, the posterior slope. We hypothesized that (1) there are large subject-to-subject variations in terms of slopes, the depth of concavity of the medial plateau, and the extent of convexity of the lateral plateau; (2) medial tibial slope and lateral tibial slope are different within subjects; (3) there are sex-based differences in the slopes as well as concavities and convexities of the tibial plateau; and (4) age is not associated with any of the measured parameters., Methods: The medial, lateral, and coronal slopes and the depth of the osseous portion of the tibial plateau were measured with use of sagittal and coronal magnetic resonance images that were made for thirty-three female and twenty-two male subjects, and differences between the sexes with respect to these four parameters were assessed. Within-subject differences between the medial and lateral tibial slopes also were assessed. Correlation tests were performed to examine the existence of a linear relationship between various slopes as well as between slopes and subject age., Results: The range of subject-to-subject variations in the tibial slopes was substantive for males and females. However, the mean medial and lateral tibial slopes in female subjects were greater than those in male subjects (p < 0.05). In contrast, the mean coronal tibial slope in female subjects was less than that in male subjects (p < 0.05). The correlation between medial and lateral tibial slopes was poor. The within-subject difference between medial and lateral tibial slopes was significant (p < 0.05). No difference in medial tibial plateau depth was found between the sexes. The subchondral bone on the lateral part of the tibia, within the articulation region, was mostly flat. Age was not associated with the observed results., Conclusions: The geometry of the osseous portion of the tibial plateau is more robustly explained by three slopes and the depth of the medial tibial condyle.