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23260577 | Automated parallel synthesis of 5'-triphosphate oligonucleotides and preparation of chemically modified 5'-triphosphate small interfering RNA. | A fully automated chemical method for the parallel and high-throughput solid-phase synthesis of 5'-triphosphate and 5'-diphosphate oligonucleotides is described. The desired full-length oligonucleotides were first constructed using standard automated DNA/RNA solid-phase synthesis procedures. Then, on the same column and instrument, efficient implementation of an uninterrupted sequential cycle afforded the corresponding unmodified or chemically modified 5'-triphosphates and 5'-diphosphates. The method was readily translated into a scalable and high-throughput synthesis protocol compatible with the current DNA/RNA synthesizers yielding a large variety of unique 5'-polyphosphorylated oligonucleotides. Using this approach, we accomplished the synthesis of chemically modified 5'-triphosphate oligonucleotides that were annealed to form small-interfering RNAs (ppp-siRNAs), a potentially interesting class of novel RNAi therapeutic tools. The attachment of the 5'-triphosphate group to the passenger strand of a siRNA construct did not induce a significant improvement in the in vitro RNAi-mediated gene silencing activity nor a strong specific in vitro RIG-I activation. The reported method will enable the screening of many chemically modified ppp-siRNAs, resulting in a novel bi-functional RNAi therapeutic platform. |
23260575 | West Nile virus infection among humans, Texas, USA, 2002-2011. | We conducted an epidemiologic analysis to document West Nile virus infections among humans in Texas, USA, during 2002-2011. West Nile virus has become endemic to Texas; the number of reported cases increased every 3 years. Risk for infection was greatest in rural northwestern Texas, where Culex tarsalis mosquitoes are the predominant mosquito species. |
23260573 | [An ANCA negative limited form of granulomatosis with polyangiitis (Wegener's granulomatosis) affecting the cavernous sinus]. | Granulomatosis with polyangeitis (Wegener's granulomatosis) (GPA) is a granulomatous vasculitis associated with antineutrophil cytoplasmic antibodies (ANCA). Affected organs usually include upper and lower respiratory tracts, and kidneys. Limited forms of GPA may affect the central nervous system (vasculitis, hypertrophic pachymeningitis, encephalitis), a location in which diagnosis is often uneasy. We report a 74-year-old woman who presented with a limited form of GPA affecting the cavernous sinus. Diagnosis was considered in view of a retrospectively suggestive clinical presentation, compatible cerebral MRI and temporal artery biopsy, despite the absence of ANCA. It was supported by a favourable outcome with cyclophosphamide administration. GPA presenting as a cavernous sinus syndrome is rare. Three co-existing pathogenic mechanisms may be involved in GPA affecting the central nervous system: contiguous invasion from nasal or orbitary granulomatous sites, vasculitis, or primary intra-cerebral granulomatous inflammation. Lack of biopsy evidence of affected tissues and ANCA negativity should not delay diagnosis and appropriate therapeutic management in central nervous system GPA. |
23260572 | Ex utero intrapartum treatment procedure for management of congenital high airway obstruction syndrome in a vertex/breech twin gestation. | Congenital high airway obstruction syndrome (CHAOS) is one indication for the ex utero intrapartum treatment (EXIT), which is used to secure the fetal airway, while fetal oxygenation is maintained by uteroplacental circulation. We report a successful EXIT procedure in a twin gestation in which one child had CHAOS while the other was a healthy child without any congenital abnormalities. After version of Twin B to allow for delivery of Twin A, Twin B underwent airway evaluation and tracheostomy for laryngeal atresia prior to delivery. |
23260571 | Computational estimation of fluid mechanical benefits from a fluid deflector at the distal end of artificial vascular grafts. | Intimal hyperplasia at the distal anastomosis is considered to be an important determinant for arterial and arteriovenous graft failure. The connection between unhealthy hemodynamics and intimal hyperplasia motivates the use of computational fluid dynamics modeling to search for improved graft design. However, studies on the fluid mechanical impact on intimal hyperplasia at the suture line intrusion have previously been scanty. In the present work, we focus on intimal hyperplasia at the suture line and illustrate potential benefits from the introduction of a fluid deflector to shield the suture line from unhealthily high wall shear stress. |
23260570 | Early detection of coronary artery disease in patients studied with magnetocardiography: an automatic classification system based on signal entropy. | We propose an automatic system for the classification of coronary artery disease (CAD) based on entropy measures of MCG recordings. Ten patients with coronary artery narrowing ≥ or ≤ 50% were categorized by a multilayer perceptron (MLP) neural network based on Linear Discriminant Analysis (LDA). Best results were obtained with MCG at rest: 99% sensitivity, 97% specificity, 98% accuracy, 96% and 99% positive and negative predictive values for single heartbeats. At patient level, these results correspond to a correct classification of all patients. The classifier's suitability to detect CAD-induced changes on the MCG at rest was validated with surrogate data. |
23260568 | Strontium substitution for calcium in lithogenesis. | Strontium has chemical similarity to calcium, which enables the replacement of calcium by strontium in biomineralization processes. Incorporating strontium into human bone and teeth has been studied extensively but little research has been performed of the incorporation of strontium into urinary calculi. We used synchrotron based x-ray fluorescence and x-ray absorption techniques to examine the presence of strontium in different types of human kidney stones. Multiple unique human stone samples were obtained via consecutive percutaneous nephrolithotomies/ureteroscopies. A portion of each stone was sent for standard laboratory analysis and a portion was retained for x-ray fluorescence and x-ray absorption measurements. X-ray fluorescence and x-ray absorption measurements determined the presence, spatial distribution and speciation of strontium in each stone sample. Traditional kidney stone analyses identified calcium oxalate, calcium phosphate, uric acid and cystine stones. X-ray fluorescence measurements identified strontium in all stone types except pure cystine. X-ray fluorescence elemental mapping of the samples revealed co-localization of calcium and strontium. X-ray absorption measurements of the calcium phosphate stone showed strontium predominately present as strontium apatite. Advanced x-ray fluorescence imaging identified strontium in all calcium based stones, present as strontium apatite. This finding may be critical since apatite is thought to be the initial nidus for calcium stone formation. Strontium is not identified by standard laboratory stone analyses. Its substitution for calcium can be reliably identified in stones from multiple calcium based stone formers, which may offer opportunities to gain insight into early events in lithogenesis. |
23260561 | Ureteroenteric anastomotic strictures after radical cystectomy-does operative approach matter? | Robot-assisted laparoscopic radical cystectomy has been increasingly used to decrease the morbidity of radical cystectomy. However, whether it truly lowers the complication rate compared to open radical cystectomy is not well established. We examined the benign ureteroenteric anastomotic stricture rates of open and robot-assisted laparoscopic radical cystectomy. In the 478 consecutive patients who underwent radical cystectomy at our institution from December 2007 to December 2011 we examined the proportion diagnosed with benign ureteroenteric anastomotic stricture. Clinicopathological variables were compared by treatment group. Cox multivariable analysis was performed to determine which patient or disease specific factors were independently associated with stricture diagnosis. A total of 375 patients (78.5%) underwent open radical cystectomy and 103 (21.5%) underwent robot-assisted laparoscopic radical cystectomy. Of the patients 45 (9.4%) were diagnosed with ureteroenteric anastomotic stricture a median of 5.3 months postoperatively. There was no difference in the stricture rate between the open and robot-assisted groups (8.5% vs 12.6%, p = 0.21). On adjusted Cox proportional hazards analysis no patient variable was independently associated with stricture diagnosis, including operative approach. Of the patients 9.4% were diagnosed with benign ureteroenteric anastomotic stricture after radical cystectomy with no significant difference in the risk of diagnosis by surgical approach. No patient or disease specific factor was independently associated with an increased risk of stricture diagnosis. Ureteroenteric anastomotic stricture is likely related to surgical technique. Continued efforts are needed to refine the technique of open and robot-assisted laparoscopic radical cystectomy to minimize the occurrence of this critical complication. |
23260557 | Renal calyceal anatomy characterization with 3-dimensional in vivo computerized tomography imaging. | Calyceal selection for percutaneous renal access is critical for safe, effective performance of percutaneous nephrolithotomy. Available anatomical evidence is contradictory and incomplete. We present detailed renal calyceal anatomy obtained from in vivo 3-dimentional computerized tomography renderings. A total of 60 computerized tomography urograms were randomly selected. The renal collecting system was isolated and 3-dimensional renderings were constructed. The primary plane of each calyceal group of 100 kidneys was determined. A coronal maximum intensity projection was used for simulated percutaneous access. The most inferior calyx was designated calyx 1. Moving superiorly, the subsequent calyces were designated calyx 2 and, when present, calyx 3. The surface rendering was rotated to assess the primary plane of the calyceal group and the orientation of the select calyx. The primary plane of the upper pole calyceal group was mediolateral in 95% of kidneys and the primary plane of the lower pole calyceal group was anteroposterior in 95%. Calyx 2 was chosen in 90 of 97 simulations and it was appropriate in 92%. Calyx 3 was chosen in 7 simulations but it was appropriate in only 57%. Calyx 1 was not selected in any simulation and it was anteriorly oriented in 75% of kidneys. Appropriate lower pole calyceal access can be reliably accomplished with an understanding of the anatomical relationship between individual calyceal orientation and the primary plane of the calyceal group. Calyx 2 is most often appropriate for accessing the anteroposterior primary plane of the lower pole. Calyx 1 is most commonly oriented anterior. |
23260554 | Microdenervation of the spermatic cord for chronic scrotal content pain: single institution review analyzing success rate after prior attempts at surgical correction. | Microdenervation of the spermatic cord is an effective treatment for men with intractable scrotal content pain. We evaluated a single center experience, analyzing patients in whom prior surgical attempts had failed to correct pain who subsequently underwent microdenervation of the spermatic cord. A retrospective chart review of 68 patients who underwent microdenervation of the spermatic cord from 2006 to 2010 was performed. Prior ipsilateral surgical procedures with the intent to correct scrotal content pain were selected, identifying 31 testicular units. Chart review was performed on 68 men with mean age of 42 years at presentation and a mean followup of 10 months. Patients in whom prior surgical correction had failed and who subsequently had microdenervation of the spermatic cord had a mean postoperative pain score of 3 (range 0 to 10) with an average decrease in pain of 67%. Those who had not undergone a prior attempt at surgical correction had a mean post-microdenervation of the spermatic cord pain score of 2 (range 0 to 10) and an average pain decrease of 79% which did not differ statistically from those in whom prior surgery failed. In addition, 50% of men who had undergone surgery before microdenervation of the spermatic cord had complete relief of pain after microdenervation of the spermatic cord vs 64% of those who had not undergone previous surgery. Men with chronic scrotal content pain in whom prior attempts to correct pain have failed have similar, albeit lower, success rates as those without prior surgical intervention. Therefore, men with chronic scrotal content pain in whom prior surgical management has failed and who have a positive spermatic cord block should be considered candidates for microdenervation of the spermatic cord. |
23260553 | Use of biomarkers to assess tissue specific androgen adequacy: defining male hypogonadism. | The criteria for normal testosterone have been established by expert consensus rather than by evidence. We determined whether a cutoff point for normal could be established using biomarkers. We performed an exploratory investigation of 1,492 hypogonadal men pooled from 7 registration trials. Serum testosterone, prostate specific antigen and hematocrit were measured at baseline and after 90 days of continuous testosterone replacement therapy. Baseline prostate specific antigen, percent change in prostate specific antigen and hematocrit appeared to be most strongly related to baseline serum testosterone. Subgroup analysis and visual inspection of linear spline fit of these data suggested an approximate serum testosterone cutoff for normal of 300 ng/dl for percent change in hematocrit, and 200 ng/dl for baseline prostate specific antigen and percent change in prostate specific antigen. This exploratory study revealed considerable variation among individuals and target tissues in individuals. Further study should be performed using standardized assays in a broader population. |
23260552 | Isolated upper pole access in percutaneous nephrolithotomy: a large-scale analysis from the CROES percutaneous nephrolithotomy global study. | We analyzed the indications for and outcomes of percutaneous nephrolithotomy using upper pole access. Between 2007 and 2009 prospective data were collected by the Clinical Research Office of the Endourological Society (CROES) from consecutive patients at 96 centers globally. Data on 4,494 patients were included in this analysis. Patients were divided into upper and lower pole access groups based on the location of percutaneous renal access. Preoperative characteristics and outcomes were compared between the 2 groups by univariate and multivariate tests. The upper pole access group had more staghorn stones (21.7% vs 15.5%, p <0.001) and a greater stone burden (mean ± SD 476 ± 390.5 vs 442 ± 344.9 mm(2), p = 0.091). Mean operative time was 92.4 ± 46.1 and 75.1 ± 41.3 minutes in the upper and lower pole groups, respectively (p <0.001). The stone-free rate was lower in the upper pole access group (77.1% vs 81.6%, p = 0.030). The overall complication rate was higher in the upper pole group with a higher incidence of hydrothorax (5.8% vs 1.5%) but a lower incidence of pelvic perforation (1.8% vs 3.2%). Mean hospital stay was longer in the upper pole group (p = 0.048). Success and complication rates were similar in upper pole access subgroups, defined as definitive (staghorn and isolated upper calyceal stones) and elective (pelvic, middle calyceal and lower pole stones) indications. Isolated upper pole access is indicated in a select group of patients with complex stones. Upper calyceal and staghorn stones are more commonly managed by upper pole access, which is associated with a higher complication rate and longer hospital stay as well as a lower stone-free rate due to procedure complexity. |
23260551 | A comparison of models for predicting sperm retrieval before microdissection testicular sperm extraction in men with nonobstructive azoospermia. | We developed an artificial neural network and nomogram using readily available clinical features to model the chance of identifying sperm with microdissection testicular sperm extraction by readily available preoperative clinical parameters for men with nonobstructive azoospermia. We reviewed the records of 1,026 men who underwent microdissection testicular sperm extraction. Patient age, follicle-stimulating hormone level, testicular volume, history of cryptorchidism, Klinefelter syndrome and presence of varicocele were included in the models. For the artificial neural network the data set was divided randomly into a training set (75%) and a test set (25%) with n1/n2 cross validation used to evaluate model accuracy, and then modeled with a neural computational system. In addition, a nomogram with calibration plots was developed to predict sperm retrieval with microdissection testicular sperm extraction. We compared these models to logistic regression. The ROC area for the neural computational system in the test set was 0.641. The neural network correctly predicted the outcome in 152 of the 256 test set patients (59.4%). The nomogram AUC was 0.59 and adequately calibrated. Multivariable logistic regression demonstrated patient age, history of Klinefelter syndrome and cryptorchidism to be significant predictors of sperm retrieval (p <0.05). However, follicle-stimulating hormone and testicular volume were not significant by internal validation. We modeled a combination of well described preoperative clinical parameters to predict sperm retrieval using a neural computational system and nomogram with acceptable predictive values. The generalizability of these findings requires external validation. |
23260550 | Concomitant intramuscular human chorionic gonadotropin preserves spermatogenesis in men undergoing testosterone replacement therapy. | Testosterone replacement therapy results in decreased serum gonadotropins and intratesticular testosterone, and impairs spermatogenesis, leading to azoospermia in 40% of patients. However, intratesticular testosterone can be maintained during testosterone replacement therapy with co-administration of low dose human chorionic gonadotropin, which may support continued spermatogenesis in patients on testosterone replacement therapy. We retrospectively reviewed the records of hypogonadal men treated with testosterone replacement therapy and concomitant low dose human chorionic gonadotropin. Testosterone replacement consisted of daily topical gel or weekly intramuscular injection with intramuscular human chorionic gonadotropin (500 IU) every other day. Serum and free testosterone, estradiol, semen parameters and pregnancy rates were evaluated before and during therapy. A total of 26 men with a mean age of 35.9 years were included in the study. Mean followup was 6.2 months. Of the men 19 were treated with injectable testosterone and 7 were treated with transdermal gel. Mean serum hormone levels before vs during treatment were testosterone 207.2 vs 1,055.5 ng/dl (p <0.0001), free testosterone 8.1 vs 20.4 pg/ml (p = 0.02) and estradiol 2.2 vs 3.7 pg/ml (p = 0.11). Pretreatment semen parameters were volume 2.9 ml, density 35.2 million per ml, motility 49.0% and forward progression 2.3. No differences in semen parameters were observed during greater than 1 year of followup. No impact on semen parameters was observed as a function of testosterone formulation. No patient became azoospermic during concomitant testosterone replacement and human chorionic gonadotropin therapy. Nine of 26 men contributed to pregnancy with the partner during followup. Low dose human chorionic gonadotropin appears to maintain semen parameters in hypogonadal men on testosterone replacement therapy. Concurrent testosterone replacement and human chorionic gonadotropin use may preserve fertility in hypogonadal males who desire fertility preservation while on testosterone replacement therapy. |
23260549 | Localization of sperm during microdissection testicular sperm extraction in men with nonobstructive azoospermia. | We determined the location where sperm were identified during microdissection testicular sperm extraction and characterized the subset of patients for whom complete bilateral exploration was most beneficial. A total of 900 men underwent a first attempt at microdissection testicular sperm extraction. Sperm extraction began with an initial wide incision in the larger testis. If no sperm were identified, the deeper tissue was extensively microdissected. A similar technique was used on the contralateral testis if no sperm were found on the initial side. In 474 men (52.6%) sperm were identified at the first microdissection testicular sperm extraction. Of these men 308 (65%) had sperm identified through the initial wide incision alone. In men with lower preoperative follicle-stimulating hormone, larger testicular volume, a varicocele history and hypospermatogenesis on preoperative or intraoperative diagnostic biopsy there was a greater chance of finding sperm in the initial wide incision alone (p <0.05). Only 40 of the 506 men (8%) who underwent bilateral testicular microdissection had sperm found on the contralateral side when no sperm were identified on the initial side. In men with Klinefelter syndrome and small testes the chance of sperm retrieval was higher on the contralateral side after negative unilateral microdissection (p <0.05). More than a third of the men with nonobstructive azoospermia required complete microdissection of the testes to identify sperm. Sperm were found on the contralateral side in up to 8% of the men in whom no sperm were identified in the initial testis. |
23260548 | Involvement of oxidative stress and mitochondrial apoptosis in the pathogenesis of pelvic organ prolapse. | Biomechanical weakness of the pelvic supportive structures has been proposed to be a cause of pelvic organ prolapse. However, the molecular mechanism involved in these changes is not completely understood. In this investigation we evaluated oxidative stress biomarkers in the uterosacral ligaments of women with pelvic organ prolapse and compared them with those of women with normal support. In addition, mitochondrial apoptosis was examined. Samples were collected from 26 women with advanced stage pelvic organ prolapse and 29 age matched controls. The expression levels of 8-OHdG and 4-hydroxy-2-nonenal in the uterosacral ligaments were measured using immunohistochemistry. To assess mitochondrial apoptosis we performed TUNEL assay, immunohistochemistry for cleaved caspase-3 and cytochrome c, and Western blot analyses for cleaved caspase-3 and caspase-9. The mean percentage of cells immunopositive for 8-OHdG, 4-hydroxy-2-nonenal, TUNEL, cleaved caspase-3 and cytochrome c in the uterosacral ligaments was significantly higher in patients with pelvic organ prolapse than in controls. Similarly, Western blot analysis revealed increased expression of cleaved caspase-3 and caspase-9 in patients with pelvic organ prolapse. Correlation analyses revealed significant positive correlations between the percentage of cells immunopositive for 8-OHdG or 4-hydroxy-2-nonenal and markers of mitochondrial apoptosis. Analyzing by pelvic organ prolapse quantification system stage according to C point, the mean percentage of cells immunopositive for 8-OHdG, 4-hydroxy-2-nonenal and cytochrome c was significantly higher in patients with pelvic organ prolapse compared to controls, regardless of stage. However, the mean percentage of TUNEL and cleaved caspase-3 positive cells was significantly higher only in patients with stage III or IV pelvic organ prolapse. Oxidative stress and increased mitochondrial apoptosis may contribute to the pathological process of pelvic organ prolapse. |
23260547 | Autologous muscle derived cell therapy for stress urinary incontinence: a prospective, dose ranging study. | In this feasibility study we assessed the 12-month safety and potential efficacy of autologous muscle derived cells (Cook MyoSite Incorporated, Pittsburgh, Pennsylvania) as therapy for stress urinary incontinence. A total of 38 women in whom stress urinary incontinence had not improved with conservative therapy for 12 or more months underwent intrasphincter injection of low doses (1, 2, 4, 8 or 16 × 10(6)) or high doses (32, 64 or 128 × 10(6)) of autologous muscle derived cells, which were derived from biopsies of their quadriceps femoris. All patients could elect a second treatment of the same dose after 3-month followup. Assessments were made at 1, 3, 6 and 12 months after the last treatment. The primary end point was the incidence and severity of adverse events. In addition, changes in stress urinary incontinence severity were evaluated by pad test, diary of incontinence episodes and quality of life surveys. Of the 38 patients 33 completed the study. Treatment related complications were limited to minor events such as pain/bruising at the biopsy and injection sites. Of patients who received 2 treatments of autologous muscle derived cells who were eligible for analysis, a higher percentage of those in the high dose vs the low dose group experienced a 50% or greater reduction in pad weight (88.9%, 8 of 9 vs 61.5%, 8 of 13), had a 50% or greater reduction in diary reported stress leaks (77.8%, 7 of 9 vs 53.3%, 8 of 15) and had 0 to 1 leaks during 3 days (88.9%, 8 of 9 vs 33.3%, 5 of 15) at final followup. Injection of autologous muscle derived cells in a wide range of doses appears safe with no major treatment related adverse events reported. In addition, treatment with autologous muscle derived cells shows promise for relieving stress urinary incontinence symptoms and improving quality of life. |
23260544 | [Objective assessment of the level of comorbidity in geriatric patients with bowel cancer: relationship between the surgical results and survival]. | Bowel cancer is increasing in prevalence in geriatrics (older than 65 years). The influence of comorbidities on the post-surgical results of bowel cancer is not well known. Our aim was to assess the comorbidities using the Charlson index in a geriatric population subjected to bowel cancer surgery, and analyse their influence on the postoperative results and the mortality rate. The study included 115 patients (over 65 years-old and with 5 years follow-up) subjected to bowel cancer surgery in the Vic General Hospital (Barcelona) between the years 2003 and 2005. Three comorbidity groups were established using the Charlson index: absent (0 points), low (1-2 points), and high (≥ 3 points). The postoperative medical and surgical complications, as well as mortality, were determined in each of the groups. The relative risk of a medical complication adjusted for age and stage was 2.7 (95% CI; 1.07-7) and 4.3 (95% CI; 1.3-14) times higher in the low and high comorbidity groups, respectively. There were no differences in post-surgical complications between the comorbidity groups. The length of hospital stay was higher in the in the high comorbidity group compared to the group with no comorbidity (17 days compared to 26 days, P=.02). The relative risk of mortality adjusted for age and stage was 1.7 (95% CI; 1.04-3) and 2.5 (95% CI; 1.3-4.6) in the low and high comorbidity groups, respectively. The presence of any level of comorbidity measured by the Charlson index is an independent predictive factor of medical complications and of an increase in overall mortality in geriatric patients subjected to bowel cancer surgery. |
23260543 | A review of the oral health-related evidence that supports the orthodontic treatment need indices. | To date, there is no evidence-based method of quantification for malocclusion. Consequently, how deviant occlusal traits should be scored and weighted relative to one another is a matter of serious debate. Orthodontic Treatment Need Indices (OTNI) use the subjective opinion of the experts, as their foundation, to define the pathological boundaries (cut-offs) of occlusal traits. This paper reviews the evidence relating malocclusions or deviated occlusal traits to oral health problems, and investigates if this evidence supports the cut-off points and the rationale used for OTNI. The relevant cited studies and reviews from the MEDLINE, Web of Science, Scopus, Cochrane databases, and scientific textbooks were used. The citation rate was confirmed by using the Google Scholar. So far, the evidence for harmful effects of deviated occlusal traits on oral health is either lacking or exists as cross-sectional (mostly) and longitudinal (a few and primarily short-term) studies. When an association was reported between a deviated occlusal trait and an oral health problem, either the strength of that association was weak, or due to methodological issues, findings were not conclusive. Consequently, establishing a cause and effect relationship is difficult. Further, commonly used OTNI do not record a full spectrum of occlusal traits, and relating their ranking or scoring systems to the available evidence is difficult. Therefore, there is little evidence to suggest that individuals with a high need (high score), as measured by OTNI, will necessarily put at risk their oral health if they turn down orthodontic therapy. OTNI have a role in the epidemiology and can be used for resource planning, but their predictive value to detect the future objective functional deficits or oral health problems is questionable. OTNI will need revalidation over time with emerging research findings. |
23260542 | A review of the evidence supporting the aesthetic orthodontic treatment need indices. | Aesthetic improvement and psychological enhancement have been cited as justifications for orthodontic treatment. This paper reviews the evidence that relates malocclusion to psychological health and quality of life and explores whether this evidence supports the most commonly used aesthetic Orthodontic Treatment Need Indices (OTNI). The relevant cited material from the MEDLINE, Web of Science, Scopus, Cochrane databases, and scientific textbooks were used. The citation rate was confirmed by using the Google Scholar. The subjective nature of aesthetic indices and the variable perception of attractiveness between clinicians and patients, and among various cultures or countries are a few limitations of aesthetic OTNI. The available evidence of mainly cross-sectional studies on the link between malocclusion and either psychosocial well-being or quality of life is not conclusive, and sometimes contradictory, to suggest these characteristics are affected by malocclusions. Further, the long-term longitudinal studies did not suggest that people with malocclusion are disadvantaged psychologically, or their quality of life would be worse off, which challenges using aesthetic OTNI to assess the social and psychological implications of malocclusion. The subjective nature of aesthetic OTNI and the minor contributory role of malocclusion in psychosocial health or quality of life undermine using aesthetic indices to assess the likely social and psychological implications of malocclusion. Consequently, using aesthetic OTNI, as a method to quantify malocclusion remains open to debate. Various soft and hard-tissue analyses are used before formulating a treatment plan (i.e., assessment of sagittal and vertical skeletal relationships). The addition of a shortened version of these analyses to the aesthetic OTNI can be a good substitute for the aesthetic components of OTNI, if an assessment of the aesthetic aspects of malocclusion is intended. This reduces subjectivity and improves the validity of the OTNI that incorporate an aesthetic component. |
23260541 | Clinical photographs: the gold standard, an update. | This survey is an update of a survey that was originally carried out in 1999 and published in 2001. Over the last 10 years the prevalence of digital photography in orthodontics has increased beyond measure and the study was to document any effects of this change. The opinions of 69 orthodontists from many European countries, as to what would be considered good practice with regards to intra and extra-oral photography with modern digital camera equipment, were sought. A written survey was distributed to the participants and collected by hand a few minutes later, once completed. A comparison was then made between current practice and what was considered best practice at the turn of the millennium. The main change was the widespread move from conventional to digital photography throughout Europe. This has resulted in a reduction in the cost of photographing each and every case on multiple occasions throughout treatment. The move to digital photography offers many advantages to orthodontists. High quality photographic documentation is almost routinely taken throughout treatment with little direct cost to the clinician. |
23260540 | Determining skeletal maturation using insulin-like growth factor I (IGF-I) test. | To investigate the validity of Insulin like Growth Factor -1(IGF-1) as a skeletal maturity indicator by comparing serum IGF-1 levels with the stages in cervical vertebral maturation (CVM) and in the middle phalanx of the third finger (MP3). The study population was selected by using simple random sampling technique and consisted of 30 female subjects in the age range of 8-23 years who had blood sample, cephalometric and MP3 radiographs taken on the same day. Serum IGF-I estimation was carried out on the blood samples using chemiluminescence immunoassay (CLIA) method. CVM was evaluated using method by Baccetti et al and MP3 staging was done using Rajagopal & Kansal method. Mean IGF-1 level between the stages was compared by Kruskal-Wallis and Mann Whitney test. Serum IGF-1 levels in females correlate well with skeletal maturity determined by CVM and MP3 stages and increase sharply during early pubertal stages followed by a decrease in late puberty. In addition we hypothesis that serum IGF-1 testing can be undertaken as a preliminary screening test in patients in whom the orthodontist predicts the possibility of using myofunctional appliance but in whom the chronologic age is not suggestive for a growth modification therapy. The finding of the study highlights the fact that the serum IGF-1 estimation can be a valuable tool in assessing skeletal maturation. |
23260539 | Relationship between dental crowding, skeletal base lengths, and dentofacial measurements. | The objectives of this study were to study the correlation between dental crowding, skeletal base lengths, and dentofacial measurements. Pretreatment dental casts and lateral cephalograms of randomly selected 45 Class I orthodontic cases divided into two groups according to the severity of mandibular crowding were evaluated. Group 1 comprised 15 patients with mandibular crowding less than 3mm while group 2 comprised 30 patients with mandibular crowding of 3mm or more. Maxillary and mandibular dental crowding and dentofacial measurements were compared between the two groups. For correlations the whole sample was combined to a single group where crowding was used as a continuous variable. The only significant difference (p=0.000) between the two groups was in the amount of dental crowding in the lower arch. Direct moderate correlation (r=0.45; p=0.002) between maxillary crowding and mandibular crowding, direct high correlation (r=0.68; p=0.000) between maxillary base length (Co-A) and mandibular base length (Co-Gn) and also direct high correlation (r=0.74; p=0.000) between maxillary base position (SNA angle) and mandibular base position (SNB angle) were detected. Correlation between maxillary incisor position and facial vertical dimension measured by the MP to SN angle showed inverse moderate correlation. Correlation between mandibular incisor position and the anteroposterior jaw relationship measured by the ANB angle showed direct moderate correlation. Results showed the presence of correlation between the skeletal dimensions and the absence of correlation between dental crowding and the same measurements. Results suggest that dental crowding is independent of the skeletal measurements. |
23260538 | Is postural platform suited to study correlations between the masticatory system and body posture? A study of repeatability and a meta-analysis of reported variations. | To evaluate the repeatability of different static posturographic parameters with regard to the analysis of correlations between the masticatory system and body posture. In 15 healthy subjects (26.4±3.7 years, 9 females and 6 males) with no malocclusion, posturographic recordings were carried out by vertical force platform under mandibular rest position (RP) and dental intercuspidal position (ICP). Six different posturographic parameters were recorded at baseline, 30 min, 1 day and 7 days. Repeatability analysis was based on the method of the moment estimator (as percentage over the baseline scores, i.e. method error) and interclass correlation coefficients (ICC). Moreover, a meta-analysis of the variations in posturographic recordings between different occlusal conditions, i.e. RP vs. ICP, from previous studies was also performed. Only the sway area and velocity yielded acceptable errors and ICCs up to 14.8% and 0.94, respectively. The spatial parameters, i.e. displacement of the centre of pressure from the theoretical point, performed poorly with lowest errors and greatest ICCs of 149.0% and 0.64, respectively. At the meta-analysis, ten studies were included and a total of 281 variation scores were calculated, with most of the greater and significant variations seen for the spatial parameters. The sway area and velocity show acceptable reliability, but a threshold of 25% should be used as a true variation between two different recording conditions, i.e. RP vs. ICP. Considering that most of the previous results on the relevant correlations between the masticatory system and body posture are based on spatial parameters, with the poorest repeatability, corresponding conclusions should be interpreted with caution. |
23260537 | The effects of face mask and tongue appliance on maxillary deficiency in growing patients: a randomized clinical trial. | The purpose of this randomized trial study was to compare the effects of facemask and Tongue appliance in treatment of Class III malocclusion with maxillary deficiency in growing patients. 45 patients (22 males, 23 females) with maxillary deficiency were selected and randomly assigned to 2 groups. 22 patients (10 boys, 12 girls) with the mean age of 9.3 years±1.2 years were treated with facemask. 23 patients (12 boys, 11 girls) with the mean age of 10.1 years±0.7 years were treated by Tongue appliance. Lateral cephalograms obtained at the beginning and end of the study were analyzed. Paired t-tests and Wilcoxon test showed that SNA and ANB significantly increased in both groups. Mann-Whitney test showed that there were no statistically significant differences between the two groups except for Jarabak ratio and Upper 1 to SN. U1 to SN increased by 11.1±6.9° in fixed facemask group and 2.5±6.1° in Tongue appliance group (P<0.001). Both treatment modalities were successful in moving the maxilla forward. However, the upper incisors had more labial inclination in the facemask group. |
23260536 | The necessity to establish surgical orthodontic fellowship program for orthodontists. | Medical field is developing very rapidly and is becoming more specialized. Orthodontics is of no exception. Thus, the purpose of this study was to evaluate the necessity of establishment of surgical orthodontic fellowship program for orthodontists in order to provide them with better insight. A 10 multiple choice question survey was taken from 270 orthodontists who participated in the European Orthodontic Society Congress in Istanbul, 2011. The results were tabulated and analyzed. 52% of the respondents believed that the knowledge of treatment of orthognathic surgery patients can be significantly improved by adding a fellowship of orthognathic surgery after the residency program. Adding such program can be very constructive and will give better insight to orthodontists in regards to treatment of orthognathic patients. |
23260535 | Surgery first: an alternative approach to ortho-surgical patients. | To make a brief description of the Surgery-First approach, where surgery is performed prior to orthodontic movement. Three clinical cases involving this type of treatment are reported. The cases presented here show different approaches, providing clinicians with an idea of how to plan this type of treatment. The cases presented satisfactory results that are similar to results of the conventional technique, once a well-designed treatment plan was conducted. The Surgery-First approach is a viable technique; however, collaborative and careful planning by the orthodontists and surgeons is needed. When well planned, the results of the Surgery-First approach are similar to those of conventional surgical-orthodontic treatment. |
23260534 | Transient bacteremia consequent to tooth brushing in orthodontic patients. | The study was conducted to find out the significance of transient bacteraemia consequent to tooth brushing in patients undergoing different orthodontic procedures. The study was carried out on 75 patients categorized in the separate groups with 25 subjects in each group of fixed, removable and myofunctional appliances. A matching control of 25 dental students was taken for comparison. The data was analyzed with the help of arithmetical mean and Chi-square test. It was observed that the transient bacteraemia consequent to tooth brushing in different orthodontic treatment groups was not significantly different from that found in subjects not wearing orthodontic appliances (control group). The risk of bacterial endocarditis and other cardiac lesions is not anyway higher in the patients wearing orthodontic appliances than those who were not undergoing any orthodontic treatment. |
23260533 | Orthodontic-surgical treatment: neuromuscular evaluation in skeletal Class II and Class III patients. | The aim of this study was the evaluation of the neuromuscular response to treatment according to diagnostic phases, as a follow-up of patients under surgical orthodontic treatment. The patient sample was subdivided into sub-samples, according to clinical characteristics. All of the patients who underwent orthognathic surgery in the Department of Orthodontics (University of Milan) were subjected to periodic electromyographic evaluation of the masticatory muscles (masseter and anterior temporal muscles), and to electrokinesiographic evaluation of the mandibular movements. The patient sample comprised 80 patients (37 males; and 43 females) at the end of growth. The electromyographic instruments used in the study included a Freely and a K6-I electromyography. Statistical evaluation was carried out with the Student's t-tests for independent samples. There are many differences between the skeletal Class II and skeletal Class III patients that are shown through the analysis of these data obtained. In the beginning phases of the treatment the muscular activities were higher in the Class II patients than in the Class III patients. Nevertheless this difference was reversed at the end of the treatment. A similar difference could be found in the mandibular kinesiology, in fact the maximum mandibular opening movement was greater in the skeletal Class II patients than in the skeletal Class III patients at the beginning of the treatment. At the end of the treatment this difference was lost. At the beginning of the treatment the Class II patients showed a greater protrusive movement of the mandibular than the Class III patients. At the end the treatment however this gap was reduced without being reversed. Functional evaluation in patients in surgical orthodontic therapy is an important element in the diagnostic-therapeutic recordings, so as to reduce as much as possible any incorrect neuromuscular activity that can result in relapse. |
23260532 | Dentoskeletal effects of the fast-back molar distalizer followed by fixed appliances. | The purpose of this study was to analyze the skeletal and dentoalveolar changes induced by the Fast-Back appliance followed by fixed appliances when compared with untreated Class II controls. The treated and untreated samples consisted of 27 subjects each (16 girls and 11 boys in the Fast-Back Group, FBG; 15 girls and 12 boys in the control Group, CG) with mean ages at the start of treatment of 13 years 3 months in the FBG and 13 years 2 months in the CG. Subjects of the FBG were treated during either the pubertal or postpubertal periods. Lateral cephalograms were analyzed at 2 observation periods: before distalization (T1) and after comprehensive orthodontic treatment appliance (T2). The T1-T2 changes in the FBG were contrasted with those in the CG by means of Mann-Whitney U test (p<0.05). Treatment induced an average correction of molar relationship of 2.4mm. The significant correction of the overjet (2.1mm) was associated with a significant amount of lower incisor proclination (3.8 degrees). A significant extrusion of lower molars (1.8mm) was recorded in the FBG. The FBG showed also a significant increase in total mandibular length (Co-Gn, 2.6mm), a counterclockwise rotation of the palatal plane (1.4 degrees), an increase in anterior facial height (N-Me, 2.7 mm), and in mandibular ramus height (Co-Go, 2.6mm). The Fast-Back is an effective appliance for Class II correction during the pubertal or postpubertal periods. |
23260531 | Comparision of orofacial airway dimensions in subject with different breathing pattern. | To test the null hypothesis that there is no significant difference in the craniofacial morphology and orofacial airway dimensions between mouth breathing (MB) and nasal breathing (NB) subjects. Lateral cephalometric radiographs of 34 MB subjects (mean age: 12.8±1.5 years; range: 12.0-15.2 years) and 33 NB subjects (mean 13.9±1.3 years; age range: 12.2-15.8 years) with Class I occlusion were examined. Totally, 34 measurements (27 craniofacial and 7 orofacial airway) were evaluated. Group differences were statistically evaluated by independent samples t-test at p<0.05 levels. Statistical comparisons showed that SNA (p<0.01), ANB (p<0.01), A to N perp (p<0.05), convexity (p<0.05), IMPA (p<0.05) and overbite (p<0.05) measurements were significantly lower in MB group when compared to NB group. However, SN-MP (p<0.01) and PP-GoGn (p<0.01) from angular measurements and S-N (p<0.05) and anterior facial height (p<0.05) from linear measurements were significantly higher in MB subjects. Among orofacial airway measurements, only upper posterior airway space was found significantly higher(p<0.001) in MB than NB subjects. The null hypothesis was rejected. Mouth breathing affects craniofacial morphology and orofacial airway dimensions. |
23260530 | Success of miniscrews used as anchorage for orthodontic treatment: analysis of different factors. | To examine factors involved in clinical success of miniscrew implants used for orthodontic anchorage in the upper jaw. One hundred and forty-four patients (93 females and 51 males) were fitted with a total of 324 miniscrew implants of two different morphologies (cylindrical and conical), and of different lengths and diameters. The clinical factors examined were screw length, side of insertion, miniscrew shape and diameter, bone quality, skeletal type, and relationship between bone quality and skeletal type and patient age. The mean overall success rate of the implants was 91.4%. The length and shape of the miniscrews significantly influenced the success rate, whereas side of insertion (left or right), screw diameter and skeletal type showed no significant effects. Poor (soft) bone quality and good (hard) bone quality are risk factors for miniscrew failure, with the best results obtained when the screws are inserted into bone of medium quality (10-15Ncm). In the posterior areas of the upper jaw, long, conical miniscrews showed a significantly greater success rate. An insertion torque of 10 Ncm to 15 Ncm is also a significant index of higher success rate. |
23260528 | Application of partial sliding mode in guidance problem. | In this paper, the problem of 3-dimensional guidance law design is considered and a new guidance law based on partial sliding mode technique is presented. The approach is based on the classification of the state variables within the guidance system dynamics with respect to their required stabilization properties. In the proposed law by using a partial sliding mode technique, only trajectories of a part of states variables are forced to reach the partial sliding surfaces and slide on them. The resulting guidance law enables the missile to intercept highly maneuvering targets within a finite interception time. Effectiveness of the proposed guidance law is demonstrated through analysis and simulations. |
23260526 | Enhancement of the citrus immune system provides effective resistance against Alternaria brown spot disease. | In addition to basal defense mechanisms, plants are able to develop enhanced defense mechanisms such as induced resistance (IR) upon appropriate stimulation. We recently described the means by which several carboxylic acids protect Arabidopsis and tomato plants against fungi. In this work, we demonstrate the effectiveness of hexanoic acid (Hx) in the control of Alternaria brown spot (ABS) disease via enhancement of the immune system of Fortune mandarin. The application of 1mM Hx in irrigation water to 2-year-old Fortune plants clearly reduced the incidence of the disease and led to smaller lesions. We observed that several of the most important mechanisms involved in induced resistance were affected by Hx application. Our results demonstrate enhanced callose deposition in infected plants treated with Hx, which suggests an Hx priming mechanism. Plants treated with the callose inhibitor 2-DDG were more susceptible to the fungus. Moreover, polygalacturonase-inhibiting protein (PGIP) gene expression was rapidly and significantly upregulated in treated plants. However, treatment with Hx decreased the levels of reactive oxygen species (ROS) in infected plants. Hormonal and gene analyses revealed that the jasmonic acid (JA) pathway was activated due to a greater accumulation of 12-oxo-phytodienoic acid (OPDA) and JA along with a rapid accumulation of JA-isoleucine (JA-Ile). Furthermore, we observed a more rapid accumulation of abscisic acid (ABA), which could act as a positive regulator of callose deposition. Thus, our results support the hypothesis that both enhanced physical barriers and the JA signaling pathway are involved in hexanoic acid-induced resistance (Hx-IR) to Alternaria alternata. |
23260525 | [Mechanisms underlying post-inflammatory hyperpigmentation: lessons from solar lentigo]. | Hyperpigmentation of the skin is a common dermatologic condition in all skin types but most prominent in brown-skinned population. In skin of color any inflammation or injury can be accompanied by alterations in pigmentation (hyper/hypo-pigmentation). Postinflammatory hyperpigmentation (PIH) can be observed in many skin conditions including acne, eczema, and contact dermatitis. In the control of skin pigmentation, parallel to the cross-talk between keratinocytes and melanocytes, increasing evidence has underlined the crucial role exerted by the interactions between mesenchymal and epithelial cells through the release of fibroblast-derived growth factors. Among these factors, the keratinocyte growth factor (KGF), alone or in combination with interleukin-1α, induces melanin deposition in vitro and hyperpigmented lesions in vivo. Furthermore, a moderate increase of KGF and a high induction of its receptor have been shown in solar lentigo lesions, suggesting the involvement of this growth factor in the onset of the hyperpigmented spots. Several studies highlight the possible contribution of the fibroblast-derived melanogenic growth factors to the hyperpigmentated lesions, in the context of the mesenchymal - epithelial interactions modulating melanocyte functions. |
23260524 | [Melasma and aspects of pigmentary disorders in Asians]. | Pigmentary changes in Asians are larger problems and more important features of aging than wrinkles. Melasma is a commonly observed epidermal hypermelanosis of the face in Asians. The altered dermal structures and impaired basement membrane are thought to have an influence on the development of epidermal hyperpigmentation of melasma. Dermal hyperpigmentary diseases are particularly common in Asians. Acquired bilateral melanosis of the neck is a characteristic dermal melanotic condition primarily of the neck in peri-menopausal women. It is characterized by marked accumulation of dermal pigment with perivascular lymphocytic infiltration. The cases seem to represent a continuum of Riehl's melanosis. Subclinical injury or inflammation may play a role as possible causative factors for the development of the pigmentation. |
23260523 | [Considerations on photoprotection and skin disorders]. | Excessive exposure to solar or artificial sources of UV radiation is deleterious to the skin and can cause or worsen several diseases. Detrimental effects of UV radiation exert an important role in the development of skin cancers, cause alterations on the immune response, and act as a trigger or aggravating factor for pigmentary disorders. A group of measures, including education, change of habits, use of physical barriers and sunscreens constitutes a significant part of the treatment of many skin disorders and are valuable preventive tools. This article summarizes the relevant studies addressing these issues, emphasizing the many aspects of photoprotection. |
23260522 | [Pigmentary lesions in patients with increased DNA damage due to defective DNA repair]. | The occurrence of abnormally pigmented skin lesions is a common phenomenon and often associated with the influence of ultraviolet radiation (UV) and other sources of DNA damage. Pigmentary lesions induced by UV radiation and other sources of DNA damage occur in healthy individuals, but human diseases with defective DNA repair represent important models which allow the investigation of possible underlying molecular mechanisms leading to hypo- and hyperpigmentations. There are several hereditary diseases which are known to go along with genetic defects of DNA repair mechanisms comprising Xeroderma pigmentosum (XP), Cockayne syndrome (CS), Trichothiodystrophy (TTD), Werner syndrome (WS), Bloom syndrome (BS), Fanconi anemia (FA) and Ataxia telangiectasia (AT). These diseases share clinical characteristics including poikilodermatic skin changes such as hypo-and hyperpigmentation. Since UV radiation is the most common source of DNA damage which can cause pigmentary lesions both in healthy individuals and in patients with genetic deficiency in DNA repair, in the present article, we focus on pigmentary lesions in patients with XP as an example of a disease associated with genetic defects in DNA repair. |
23260521 | [Normal and abnormal skin color]. | The varieties of normal skin color in humans range from people of "no color" (pale white) to "people of color" (light brown, dark brown, and black). Skin color is a blend resulting from the skin chromophores red (oxyhaemoglobin), blue (deoxygenated haemoglobin), yellow-orange (carotene, an exogenous pigment), and brown (melanin). Melanin, however, is the major component of skin color ; it is the presence or absence of melanin in the melanosomes in melanocytes and melanin in keratinocytes that is responsible for epidermal pigmentation, and the presence of melanin in macrophages or melanocytes in the dermis that is responsible for dermal pigmentation. Two groups of pigmentary disorders are commonly distinguished: the disorders of the quantitative and qualitative distribution of normal pigment and the abnormal presence of exogenous or endogenous pigments in the skin. The first group includes hyperpigmentations, which clinically manifest by darkening of the skin color, and leukodermia, which is characterized by lightening of the skin. Hypermelanosis corresponds to an overload of melanin or an abnormal distribution of melanin in the skin. Depending on the color, melanodermia (brown/black) and ceruloderma (blue/grey) are distinguished. Melanodermia correspond to epidermal hypermelanocytosis (an increased number of melanocytes) or epidermal hypermelanosis (an increase in the quantity of melanin in the epidermis with no modification of the number of melanocytes). Ceruloderma correspond to dermal hypermelanocytosis (abnormal presence in the dermis of cells synthesizing melanins) ; leakage in the dermis of epidermal melanin also exists, a form of dermal hypermelanosis called pigmentary incontinence. Finally, dyschromia can be related to the abnormal presence in the skin of a pigment of exogenous or endogenous origin. |
23260520 | [Medical makeup: the correction of hyperpigmentation disorders]. | Medical makeup corrects skin tone imperfections with dermo-cosmetic products, which bring together tolerance efficacy, colour neutralization and sun protection. Highly suitable for imperfections caused by hyperpigmentation, it allows patients affected by these disorders to cover them up effectively and discretely, giving them a better quality of life. |
23260519 | [Dermocosmetic management of hyperpigmentations]. | Hyperpigmentations are very frequent situations that can have considerable impact on the quality of life of affected individuals. However, even if the esthetic prejudice they generate is undeniable, lentigo and melasma are benign conditions that require above all a risk-free management. In addition to the dermatological procedures (peeling, laser, etc.) and the topical drugs available to the dermatologist, there remains significant room for depigmenting dermocosmetic products. These products succeeded to transpose features of the classic pharmaceutical formula invented by Kligman from which they were inspired to the field of dermocosmetics. They comprise activators of epidermal turn-over, skin exfoliants, and active ingredients that interfere with the different stages of melanogenesis, without having the side effects of hydroquinone whose usage remains limited to the field of prescription drugs. Antioxidants are a particularly interesting addition because they participate in reducing cutaneous inflammation and efficiently complete the action of the other components of a depigmenting formula. It is important to remind the aggravating role that sun exposure has on hyperpigmentations. Therefore, measures of rigorous photoprotection are mandatory. Medical makeup, transitory or definite, is an interesting option for the management of hyperpigmentations. Consequently, depigmenting dermocosmetics, used in monotherapy but - most frequently - in combination with dermatological procedures, can be used in literally all types of hyperpigmentations with an efficacy that is dependent on the specific etiology. They are suited to be part of a treatment program that has to be adapted on a case-by-case basis. |
23260518 | [Lasers]. | Lasers are a very effective approach for treating many hyperpigmented lesions. They are the gold standard treatment for actinic lentigos and dermal hypermelanocytosis, such as Ota nevus. Becker nevus, hyperpigmented mosaicisms, and lentigines can also be successfully treated with lasers, but they could be less effective and relapses can be observed. However, lasers cannot be proposed for all types of hyperpigmentation. Thus, freckles and café-au-lait macules should not be treated as the relapses are nearly constant. Due to its complex pathophysiology, melasma has a special place in hyperpigmented dermatoses. Q-switched lasers (using standard parameters or low fluency) should not be used because of consistent relapses and the high risk of post-inflammatory hyperpigmentation. Paradoxically, targeting the vascular component of the melasma lesion with lasers could have a beneficial effect. However, these results have yet to be confirmed. In all cases, a precise diagnosis of the type of hyperpigmentation is mandatory before any laser treatment, and the limits and the potential side effects of the treatment must be clearly explained to patients. |
23260517 | [Topical treatment of hyperpigmentation disorders]. | Hyperpigmentation has traditionally been a relatively difficult condition to treat, especially in darker racial ethnic groups. Multiple topical agents available act upon different steps of the pigmentation pathway. We review these topical agents, their mechanisms of action, and their effectiveness as monotherapy and in combination with other compounds. Ultimately, combination therapy is the most efficacious when considering overall depigmentation as well as treatment time required to achieve clinical improvement. |
23260506 | A randomized trial of cognitive behavioral therapy in primary care-based buprenorphine. | To determine the impact of cognitive behavioral therapy on outcomes in primary care, office-based buprenorphine/naloxone treatment of opioid dependence. We conducted a 24-week randomized clinical trial in 141 opioid-dependent patients in a primary care clinic. Patients were randomized to physician management or physician management plus cognitive behavioral therapy. Physician management was brief, manual guided, and medically focused; cognitive behavioral therapy was manual guided and provided for the first 12 weeks of treatment. The primary outcome measures were self-reported frequency of illicit opioid use and the maximum number of consecutive weeks of abstinence from illicit opioids, as documented by urine toxicology and self-report. The 2 treatments had similar effectiveness with respect to reduction in the mean self-reported frequency of opioid use, from 5.3 days per week (95% confidence interval, 5.1-5.5) at baseline to 0.4 (95% confidence interval, 0.1-0.6) for the second half of maintenance (P<.001 for the comparisons of induction and maintenance with baseline), with no differences between the 2 groups (P=.96) or between the treatments over time (P=.44). For the maximum consecutive weeks of opioid abstinence there was a significant main effect of time (P<.001), but the interaction (P=.11) and main effect of group (P=.84) were not significant. No differences were observed on the basis of treatment assignment with respect to cocaine use or study completion. Among patients receiving buprenorphine/naloxone in primary care for opioid dependence, the effectiveness of physician management did not differ significantly from that of physician management plus cognitive behavioral therapy. |
23260504 | United States counties with low black male mortality rates. | In the United States, young and middle-aged black men have significantly higher total mortality than any other racial or ethnic group. We describe the characteristics of US counties with low non-Hispanic Black or African American male mortality (ages 25-64 years, 1999-2007). Information was accessed through public data, the US Census, the US Compressed Mortality File, and the Native American Graves Repatriation Act military database. Of 1307 counties with black mortality rates classified as reliable by the National Center for Health Statistics (at least 20 deaths), 66 recorded lower mortality among black men than corresponding US whites. Most notable, 97% of the 66 counties were home to or adjacent a military installation versus 37% of comparable US counties (P<.001). Blacks in these counties had less poverty, higher percentages of elderly civilian veterans, and higher per capita income. Within these counties, national black:white disparities in mortality were eliminated for ischemic heart disease, accidents, diseases of the liver, chronic lower respiratory diseases, and mental disorder from psychoactive substance use. Application of age-, race-, ethnicity-, gender-, and urbanization-specific mortality rates from counties with relatively low mortality would reduce the black:white mortality rate ratio for black men aged 25 to 64 years from 1.67 to 1.20 nationally and to 1.00 in areas outside large central metropolitan areas. These descriptive data demonstrate a small number of communities with low mortality rates among young and middle-aged black/African American men. Their characteristics may provide clinical and public health insights to reduce these higher mortality rates in the US population. Analytic epidemiologic studies are necessary to test these hypotheses. |
23260503 | Endocarditis and risk of cancer: a Danish nationwide cohort study. | Endocarditis may be a marker for bacteremia-associated occult cancer. Intensive antibiotic treatment in endocarditis is suggested to reduce long-term cancer risk. We examined these hypotheses in a nationwide cohort study. Endocarditis patients and cancer cases were identified from the Danish National Registry of Patients and the Danish Cancer Registry during 1978-2008. We compared the incidences of various cancers among study subjects to expected incidences based on national age-, sex-, and site-specific rates. We observed 997 cancers among 8445 endocarditis patients (median follow-up of 3.5 years), reflecting an increased standardized incidence rate (SIR) of 1.61 (95% confidence interval [CI], 1.51-1.71). Cancer risk was highly elevated during the first 3 months of follow-up (SIR=8.03; 95% CI, 6.92-9.26), partly due to a 15- to 30-fold increased risk of hematological or liver cancers. Between 3-month and 5-year follow-ups, cancer incidence remained 1.5-fold higher than expected, including 2- and 4-fold increased SIRs for colorectal and liver cancers, respectively. Beyond 5 years of observation, the overall cancer SIR was 1.21 (95% CI, 1.10-1.34). Long-term associations were weak for several cancers hypothesized to be associated with antibiotic use, including prostate, gastric, and breast cancer. Endocarditis is a substantial clinical marker for presence of occult cancer. We found no evidence of decreased long-term cancer risk after antibiotic treatment for endocarditis. |
23260502 | Frontiers of therapy for patients with heart failure. | This review broadly covers advances in heart failure, which is responsible for significant morbidity, mortality, and cost in the United States. It is a heterogeneous condition, and accurate classification helps ensure appropriate application of evidence-based therapies. Hemodynamics are important in acute heart failure syndromes and may help tailor therapy. Neurohormonal modulation forms the cornerstone of chronic systolic heart failure treatment but does not affect outcomes in diastolic heart failure where management goals emphasize optimization of central volume, blood pressure, and atrial rhythm, as well as the treatment of comorbidities. Frontiers of heart failure therapy range from advances in pharmacology (novel inotropic agents and neurohormonal modulators), to cell biology (nucleic acid-based drugs and cell therapy) to biomedical engineering (devices such as ultrafiltration, biventricular pacemakers, implantable cardiac defibrillators, remote monitoring systems, and left ventricular assist devices), and to health systems (risk stratification and integrated care of comorbidities). The ultimate frontier will be to integrate these data effectively to ensure that patients with heart failure consistently receive the best evidenced-based care possible. |
23260488 | H2A.Z facilitates access of active and repressive complexes to chromatin in embryonic stem cell self-renewal and differentiation. | Chromatin modifications have been implicated in the self-renewal and differentiation of embryonic stem cells (ESCs). However, the function of histone variant H2A.Z in ESCs remains unclear. We show that H2A.Z is highly enriched at promoters and enhancers and is required for both efficient self-renewal and differentiation of murine ESCs. H2A.Z deposition leads to an abnormal nucleosome structure, decreased nucleosome occupancy, and increased chromatin accessibility. In self-renewing ESCs, knockdown of H2A.Z compromises OCT4 binding to its target genes and leads to decreased binding of MLL complexes to active genes and of PRC2 complex to repressed genes. During differentiation of ESCs, inhibition of H2A.Z also compromises RA-induced RARα binding, activation of differentiation markers, and the repression of pluripotency genes. We propose that H2A.Z mediates such contrasting activities by acting as a general facilitator that generates access for a variety of complexes, both activating and repressive. |
23260487 | Cyclin-dependent kinase inhibitor p21 controls adult neural stem cell expansion by regulating Sox2 gene expression. | In the adult brain, continual neurogenesis of olfactory neurons is sustained by the existence of neural stem cells (NSCs) in the subependymal niche. Elimination of the cyclin-dependent kinase inhibitor 1A (p21) leads to premature exhaustion of the subependymal NSC pool, suggesting a relationship between cell cycle control and long-term self-renewal, but the molecular mechanisms underlying NSC maintenance by p21 remain unexplored. Here we identify a function of p21 in the direct regulation of the expression of pluripotency factor Sox2, a key regulator of the specification and maintenance of neural progenitors. We observe that p21 directly binds a Sox2 enhancer and negatively regulates Sox2 expression in NSCs. Augmented levels of Sox2 in p21 null cells induce replicative stress and a DNA damage response that leads to cell growth arrest mediated by increased levels of p19(Arf) and p53. Our results show a regulation of NSC expansion driven by a p21/Sox2/p53 axis. |
23260470 | A color-mediated mutualism between two arthropod predators. | The nature of interactions between animals varies depending on local selection pressure, trophic status of the participants, and evolutionary circumstances. Body coloration and other visual signals may also affect animal interactions. Game theory posits that if one species provides a "service" in exchange for a "goods," a mutualism may ensue. Mutualisms between two predators are rare because of multiple conflicts of interests (but see [11, 12]). We used a nocturnal system traditionally considered kleptoparasitic to determine whether a mutualism ensues because the body coloration of the kleptoparasite is beneficial to the host. Specifically, we tested whether the silver body of the spider Argyrodes fissifrons (Theridiidae) attracts prey for the larger, duller spider Cyrtophora unicolor (Araneidae), which reciprocates by allowing A. fissifrons access to its web. When A. fissifrons were removed from C. unicolor webs, the webs intercepted fewer prey. Furthermore, covering the silver body parts of A. fissifrons also resulted in a reduction in prey interception by C. unicolor webs. We thus show that a mutualism between two arthropod predators can be mediated by the coloration of one species enhancing the foraging gains of another. |
23260469 | Selective attention in an insect visual neuron. | Animals need attention to focus on one target amid alternative distracters. Dragonflies, for example, capture flies in swarms comprising prey and conspecifics, a feat that requires neurons to select one moving target from competing alternatives. Diverse evidence, from functional imaging and physiology to psychophysics, highlights the importance of such "competitive selection" in attention for vertebrates. Analogous mechanisms have been proposed in artificial intelligence and even in invertebrates, yet direct neural correlates of attention are scarce from all animal groups. Here, we demonstrate responses from an identified dragonfly visual neuron that perfectly match a model for competitive selection within limits of neuronal variability (r(2) = 0.83). Responses to individual targets moving at different locations within the receptive field differ in both magnitude and time course. However, responses to two simultaneous targets exclusively track those for one target alone rather than any combination of the pair. Irrespective of target size, contrast, or separation, this neuron selects one target from the pair and perfectly preserves the response, regardless of whether the "winner" is the stronger stimulus if presented alone. This neuron is amenable to electrophysiological recordings, providing neuroscientists with a new model system for studying selective attention. |
23260468 | Parietal cortex codes for egocentric space beyond the field of view. | Our subjective experience links covert visual and egocentric spatial attention seamlessly. However, the latter can extend beyond the visual field, covering all directions relative to our body. In contrast to visual representations, little is known about unseen egocentric representations in the healthy brain. Parietal cortex appears to be involved in both, because lesions in it can lead to deficits in visual attention, but also to a disorder of egocentric spatial awareness, known as hemispatial neglect. Here, we used a novel virtual reality paradigm to probe our participants' egocentric surrounding during fMRI recordings. We found that egocentric unseen space was represented by patterns of voxel activity in parietal cortex, independent of visual information. Intriguingly, the best decoding performances corresponded to brain areas associated with visual covert attention and reaching, as well as to lesion sites associated with spatial neglect. |
23260467 | Severe sepsis in do-not-resuscitate patients: intervention and mortality rates. | Severe sepsis is a high-mortality disease, and early resuscitation decreases mortality. Do-not-resuscitate (DNR) status may influence physician decisions beyond cardiopulmonary resuscitation, but this has not been investigated in sepsis. Among Emergency Department (ED) severe sepsis patients, define the incidence of DNR status, prevalence of central venous catheter placement, and vasopressor administration (invasive measures), and mortality. Retrospective observational cohort of consecutive severe sepsis patients to single ED in 2009-2010. Charts abstracted for DNR status on presentation, demographics, vitals, Sequential Organ Failure Assessment (SOFA) score, inpatient and 60-day mortality, and discharge disposition. Primary outcomes were mortality, discharge to skilled nursing facility (SNF), and invasive measure compliance. Chi-squared test was used for univariate association of DNR status and outcome variables; multivariate logistic regression analyses for outcome variables controlling for age, gender, SOFA score, and DNR status. In 376 severe sepsis patients, 50 (13.3%) had DNR status. DNR patients were older (79.2 vs 60.3 years, p < 0.001) and trended toward higher SOFA scores (7 vs. 6, p = 0.07). DNR inpatient and 60-day mortalities were higher (50.5% vs. 19.6%, 95% confidence interval [CI] 15.9-44.9%; 64.0% vs. 24.9%, 95% CI 25.1-53.3%, respectively), and remained higher in multivariate logistic regression analysis (odds ratio [OR] 3.01, 95% CI 1.48-6.17; OR 3.80, 95% CI 1.88-7.69, respectively). The groups had similar rates of discharge to SNF, and in persistently hypotensive patients (n = 326) had similar rates of invasive measures in univariate and multivariate analyses (OR 1.19, 95% CI 0.45-3.15). In this sample, 13.3% of severe sepsis patients had DNR status, and 50% of DNR patients survived to hospital discharge. DNR patients received invasive measures at a rate similar to patients without DNR status. |
23260466 | GLass intact Assures Safe cervical Spine protocol. | Selective cervical spine immobilization performed by Emergency Medical Services (EMS) is being utilized with increasing frequency. These protocols, although very sensitive, still include subjective data such as "mild cervical discomfort." The aim of this study is to create an objective clinical decision rule that would enhance the selective approach for cervical spine immobilization in patients aged 16-60 years. It is hypothesized that, in a motor vehicle crash, the integrity of the involved vehicle's glass window and airbag status is an excellent objective measure for the amount of energy a vehicle occupant has experienced during the crash. GLass intact Assures Safe Spine (GLASS) is an easy and objective method for evaluation of the need for prehospital cervical spine immobilization. A retrospective cohort study was performed with sample motor vehicle crash cases to evaluate the performance of the GLASS rule. The National Accident Sampling System-Crashworthiness Data System (NASS-CDS) was utilized to investigate tow-away motor vehicle crashes, including their glass damage characteristics and occupant injury outcomes, over an 11-year period (1998-2008). Sample occupant cases selected for this study were patients aged 16-60 years, who were belt-restrained front seat occupants involved in a crash with no airbag deployment, and no glass damage before the crash. A total of 14,191 occupants involved in motor vehicle crashes were evaluated in this analysis. The results showed that the sensitivity of the GLASS rule was 95.20% (95% confidence interval [CI] 91.45-98.95%), the specificity was 54.27% (95% CI 53.44-55.09%), and the negative predictive value was 99.92% (95% CI 99.86-99.98%). The GLASS rule presents the possibility of a novel, more objective tool for cervical spine clearance. Prospective evaluation is required to further evaluate the validity of this clinical decision rule. |
23260465 | Emergency Department vancomycin use: dosing practices and associated outcomes. | Emergency Department (ED) dosing of vancomycin and its effect on outcomes has not been examined. To describe current vancomycin dosing practices for ED patients, focusing on patient factors associated with administration, dosing accuracy based on patient body weight, and clinical outcomes. Single-center, retrospective cohort study of vancomycin administered in the ED over 18 months in an academic, tertiary care ED. Data were collected on 4656 patients. Data were analyzed using a generalized estimating equations model to account for multiple doses being administered to the same patient. The ED dose was continued, unchanged, in 2560 admitted patients (83.8%). The correct dose was given 980 times (22.1%), 3143 doses (70.7%) were underdosed, and 318 were overdosed (7.2%). Increasing weight was associated with underdosing (adjusted odds ratio 1.52 per 10 kg body weight, p < 0.001). Patients who received doses of vancomycin > 20 mg/kg had longer hospital length of stay (p = 0.005); were more likely to spend ≥ 3 days in the hospital (odds ratio [OR] 1.49; 95% confidence interval [CI] 1.12-1.98, p = 0.006); and more likely to die (OR 1.88; 95% CI 1.22-2.90, p = 0.004). In this largest study to date examining ED vancomycin dosing, vancomycin was commonly given. Dosing outside the recommended range was frequent, and especially prevalent in patients with a higher body weight. The ED dose of vancomycin was frequently continued as an inpatient, regardless of dosing accuracy. There is significant room for improvement in dosing accuracy and indication. Vancomycin dosing in the ED may also affect clinical outcomes. |
23260464 | Klebsiella pneumoniae antimicrobial drug resistance, United States, 1998-2010. | We studied antimicrobial-resistant Klebsiella pneumoniae for 1998-2010 by using data from The Surveillance Network. Susceptibility results (n = 3,132,354) demonstrated significant increases in resistance to all antimicrobial drugs studied, except tetracycline. Cross-resistance among carbapenem-resistant K. pneumoniae was lower for tetracycline and amikacin. |
23260463 | Frailty and aortic valve disease. | Frailty is a common occurrence in elderly persons and is present in approximately half of the patients being screened for transcatheter aortic valve replacement (TAVR) therapy. Accurate assessment of the likelihood of benefit from intervention in the older patient with aortic stenosis is critical with both surgical aortic valve replacement and TAVR now available. Whereas risk algorithms are available that are helpful in predicting outcomes in patients undergoing surgical procedures, measures of frailty are not included in the algorithms. When considering intervention in the elderly patient, the addition of frailty assessment to determine the true risk in this population is essential to determine potential benefit. Gait speed as determined by the 5-m walk test is the most commonly used single test objective measurement of frailty in patients undergoing cardiac surgery and is an independent predictor of mortality and major morbidity. Wider application of this and other objective measures of frailty in the population undergoing TAVR is necessary to determine whether it is predictive in this population also. |
23260462 | Transposition of the supra-aortic vessels before stent grafting the aortic arch and descending aorta. | Thoracic endovascular aortic repair has broadened the spectrum of treatment options for various acute and chronic thoracic aortic diseases. In clinical practice, aneurysms of the descending aorta are rarely limited to 1 segment. Thus, various surgical and endovascular options have been developed to offer treatment to those patients with more extended descending thoracic aortic disease. We have summarized the most common methods of arch rerouting, depending on the aortic involvement, emphasizing that these techniques should be used very selectively by experienced cardiovascular surgery teams. |
23260461 | Hybrid approaches in the treatment of aortic arch aneurysms: postoperative and midterm outcomes. | The combined open surgical and endovascular approach for the treatment of aortic arch aneurysms has emerged as a safe treatment modality. This platform may have an especially important role in treating patients of old age and with a greater comorbid burden. We describe our institutional experience with the hybrid aortic arch approach, with midterm outcomes. From 2005 to the present, 685 patients have undergone thoracic endovascular repair (TEVAR); 104 had a hybrid arch repair (open plus endovascular approach). Of these, 47 patients had treatment for an aortic arch aneurysm with or without a proximal ascending aortic aneurysm. All these patients had a median sternotomy approach for arch vessel debranching and antegrade with or without retrograde TEVAR stent grafting of the arch. Results from a prospectively maintained database are reported. Twenty-eight patients had type I repair, 8 patients had type II repair, and 11 patients had type III arch hybrid repair. Those with type III repair were excluded from the analysis. Stent graft deployment rate was 100% after arch vessel debranching. Mean age was 71 ± 8 years. Fourteen percent of cases involved a redo sternotomy. Average cardiopulmonary bypass time was 215 ± 64 minutes, with a crossclamp time of 70 ± 55 minutes and a circulatory arrest time of 19 ± 10 minutes. The paraplegia rate was 5.5% (n = 2), with a stroke rate of 8% (n = 3). In-hospital mortality was 8% (n = 3). There were no postoperative endoleaks. The mean length of stay was 17.2 ± 14 days. The median follow-up was 30 ± 21 months. Freedom from all-cause mortality was 71%, 60%, and 48% at 1, 3, and 5 years, respectively. The aortic reoperation rate was 2.7% (n = 1). No patient has a type 1 or 3 endoleak at latest follow-up. The hybrid approach to aortic arch aneurysm involving a zone 0 stent graft landing can be safely adopted with good midterm results in a cohort of old patients with significant comorbidity. This procedure can be performed with no type 1 or 3 endoleaks and may represent a technical advancement in the field of aortic arch surgery. |
23260460 | Postmortem and ex vivo carbon monoxide ventilation reduces injury in rat lungs transplanted from non-heart-beating donors. | We sought to determine whether ventilation of lungs after death in non-heart-beating donors with carbon monoxide during warm ischemia and ex vivo lung perfusion and after transplant would reduce ischemia-reperfusion injury and improve lung function. One hour after death, Sprague-Dawley rats were ventilated for another hour with 60% oxygen (control group) or 500 ppm carbon monoxide in 60% oxygen (CO-vent group; n=6/group). Then, lungs were flushed with 20 mL cold Perfadex, stored cold for 1 hour, then warmed to 37 °C in an ex vivo lung perfusion circuit perfused with Steen solution. At 37 °C, lungs were ventilated for 15 minutes with alveolar gas with or without 500 ppm carbon monoxide, then perfusion-cooled to 20 °C, flushed with cold Perfadex and stored cold for 2 hours. The left lung was transplanted using a modified cuff technique. Recipients were ventilated with 60% oxygen with or without carbon monoxide. One hour after transplant, we measured blood gases from the left pulmonary vein and aorta, and wet-to-dry ratio of both lungs. The RNA and protein extracted from graft lungs underwent real-time polymerase chain reaction and Western blotting, and measurement of cyclic guanosine monophosphate by enzyme-linked immunosorbent assay. Carbon monoxide ventilation begun 1 hour after death reduced wet/dry ratio after ex vivo lung perfusion. After transplantation, the carbon monoxide-ventilation group had better oxygenation; higher levels of tissue cyclic guanosine monophosphate, heme oxidase-1 expression, and p38 phosphorylation; reduced c-Jun N-terminal kinase phosphorylation; and reduced expression of interleukin-6 and interleukin-1β messenger RNA. Administration of carbon monoxide to the deceased donor and non-heart-beating donor lungs reduces ischemia-reperfusion injury in rat lungs transplanted from non-heart-beating donors. Therapy to the deceased donor via the airway may improve post-transplant lung function. |
23260459 | Medical management of thoracic aortic aneurysm disease. | The patient with thoracic aortic aneurysm disease requires careful evaluation and management over his or her lifetime. This includes assessment for the presence of an underlying genetic disorder, such as Marfan syndrome, bicuspid aortic valve disease, or a familial aortic aneurysm syndrome. Screening family members is necessary, inasmuch as up to 20% of first-degree relatives of the patient with a thoracic aortic aneurysm will also have aneurysm disease. Medical therapy is often prescribed, and beta-blocker therapy to reduce the stress on the aortic wall is usually recommended. However, very few clinical trials of pharmacologic therapy in humans with thoracic aortic aneurysm disease have been conducted. Mouse models have led to important discoveries and insight into the pathogenesis of aneurysm syndromes, and there is hope these may lead to effective therapy in people. Several studies are ongoing that examine the role of angiotensin receptor blockers in Marfan syndrome. Lifestyle modification is also important for patients with thoracic aortic aneurysm, including restrictions on physical activity, weight lifting, and recommendations about the management of pregnancy. Long-term surveillance of the aorta, even after successful surgery, is necessary for timing of prophylactic surgery and to evaluate for late complications. |
23260458 | Early results with annular support in reconstruction of the bicuspid aortic valve. | Repair of the bicuspid aortic valve may be performed in aortic regurgitation and aneurysm. Dilatation of the atrioventricular junction has been identified as a risk factor for repair failure, and we have used suture annuloplasty to correct atrioventricular junction enlargement. The objective was to compare the early results of aortic repair with and without annuloplasty. Between November 1995 and January 12, a total of 559 patients were treated with bicuspid aortic valve repair for predominant regurgitation (n = 389), aortic aneurysm (n = 158), or acute dissection (n = 12). Isolated valve repair (aortic valve repair) was performed for aortic valve regurgitation with preserved aortic dimensions (n = 208) and sinotubular junction remodeling plus valve repair for aortic aneurysm and preserved root size (n = 116). Root remodeling was used for dilatation involving the root (n = 235). In 193 patients, dilatation of the atrioventricular junction (>27 mm) was corrected with suture annuloplasty. Hospital mortality was 0.5% (n = 3); 2 patients required pacemaker implantation. Reoperation was necessary for recurrent regurgitation (n = 54) or stenosis (n = 2); 10-year freedom from reoperation was 82% but was inferior after isolated valve repair (70%, P = .007) compared with the 2 other techniques. Application of suture annuloplasty improved 3-year freedom from reoperation after isolated repair (84%) to 92% (P = .07). In all groups, the proportion of patients with no or trivial regurgitation was significantly higher with annuloplasty. Preservation of the bicuspid aortic valve is feasible in many patients. Long-term stability of the repaired valves is good; the negative impact of a dilated atrioventricular junction can be reduced by suture annuloplasty. |
23260457 | Innominate artery cannulation: an alternative to femoral or axillary cannulation for arterial inflow in proximal aortic surgery. | To evaluate the effectiveness of innominate artery cannulation in proximal aortic procedures, including those involving hypothermic circulatory arrest. A total of 68 patients underwent innominate artery cannulation with a side graft during proximal aortic surgery performed by way of a median sternotomy. The indications for surgery were proximal arch aneurysm in 43 patients (63.2%), aortic dissection in 11 patients (16.2%), total arch aneurysm in 10 patients (14.7%), and ascending aortic aneurysm in 4 patients (5.9%). Six patients (8.8%) had undergone previous sternotomy. Hypothermic circulatory arrest with antegrade cerebral perfusion was used in 64 patients (94.1%). Of the 68 patients, 63 (92.6%) received antegrade cerebral perfusion to both cerebral hemispheres. The median antegrade cerebral perfusion time was 20 minutes (range, 15.0-33.0 minutes). Seven patients had periods of circulatory arrest without antegrade cerebral perfusion for a median of 20 minutes (range, 6-33 minutes). One patient died, for 30-day mortality of 1.5%. Three patients (4.4%) had strokes, two of whom had a partial recovery. Seven patients (10.3%) developed temporary postoperative confusion that resolved successfully in all cases. Cannulating the innominate artery for arterial inflow is an alternative technique for proximal aortic surgery procedures. It is especially useful in cases requiring hypothermic circulatory arrest to deliver antegrade cerebral perfusion. |
23260456 | Update on blunt thoracic aortic injury: fifteen-year single-institution experience. | Despite improvements in the management of blunt thoracic aortic injury, mortality remains high. We report our experience with blunt thoracic aortic injury at a level 1 trauma center over the past 15 years. Between January 1, 1997, and January 1, 2012, data on 338 patients who presented with suspected blunt thoracic aortic injury were entered into the University of Texas Medical School at Houston Trauma Center Registry. A total of 175 patients (52%) underwent thoracic aortic repair; 29 (17%) had open repair with aortic crossclamping, 77 (44%) had open repair with distal aortic perfusion, and 69 (39%) had thoracic endovascular aortic repair. Outcomes were determined, including early mortality, morbidity, length of stay, and late survival. Multiple logistic regression analysis was used to compute adjusted estimates for the effects of the operative technique. The early mortality for all patients with blunt thoracic aortic injury was 41% (139/338). Early mortality was 17% (27/175) for operative aortic interventions, 4% (3/69) for thoracic endovascular aortic repairs, 31% (11/29) for open repairs with aortic crossclamping, and 14% (11/77) for open repairs with distal aortic perfusion. Survival for thoracic endovascular aortic repair at 1 year and 5 years was 92% and 87%, respectively. Survival for open repair at 1, 5, 10, and 15 years was 76%, 75%, 72%, and 68%, respectively. Blunt thoracic aortic injury remains associated with significant early mortality. Delayed selective management, when applied with open repair with distal aortic perfusion and the use of thoracic endovascular aortic repair, has been associated with improved early outcomes. The long-term durability of thoracic endovascular aortic repair is unknown, necessitating close radiographic follow-up. |
23260455 | Contemporary open aortic arch repair with selective cerebral perfusion in the era of endovascular aortic repair. | With the recent advance of endovascular aortic repair, conventional open repair for aortic arch lesions should be reassessed. We reviewed our contemporary open arch repair with selective antegrade cerebral perfusion by way of the axillary artery with deep or moderate hypothermia. From 2001 to 2011, 1007 patients (median age, 72 years) underwent open arch repair with selective cerebral perfusion through the right axillary artery and hypothermic circulatory arrest: deep (<25 °C) in 48% and moderate (25 °-28 °C) in 52%. Of the 1007 patients, 73% underwent total arch replacement and 26% emergent surgery for aneurysm rupture or acute aortic dissection. The early mortality was 4.7% for all patients. Permanent and temporary neurologic dysfunction occurred in 3.5% and 6.7%, respectively. No spinal cord injury occurred, even with moderate hypothermia. The independent predictors of in-hospital mortality included chronic obstructive pulmonary disease, liver dysfunction, chronic kidney disease, and concomitant coronary artery bypass. The independent predictors of permanent neurologic dysfunction included cerebrovascular disease, emergency surgery, and concomitant coronary artery bypass. The cumulative survival rate was 80.4% and 71.2% at 5 and 8 years, respectively. Freedom from reoperation related to the initial arch repair was 98.0% and 96.9% at 5 and 8 years, respectively. Conventional open arch repair yielded satisfactory outcomes and should remain the standard therapy, with good long-term durability in all but high-risk patients. |
23260452 | Expectations modulate heterotopic noxious counter-stimulation analgesia. | The present study examined the contribution of expectations to analgesia induced by heterotopic noxious counter-stimulation (HNCS) in healthy volunteers assigned to a control group or 1 of 3 experimental groups in which expectations were either assessed (a priori expectations) or manipulated using suggestions (hyperalgesia and analgesia). Acute shock-pain, the nociceptive flexion reflex (RIII-reflex), and shock-related anxiety were measured in response to electrical stimulations of the right sural nerve in the baseline, HNCS, and recovery periods. Counter-stimulation was applied on the contralateral forearm using a flexible cold pack. A priori expectations were strongly associated with the actual magnitude of the analgesia induced by HNCS. In comparison to the control condition, suggestions of hyperalgesia led to an increase in RIII-reflex amplitude and shock-pain, while suggestions of analgesia resulted in a greater decrease in RIII-reflex amplitude, which confirms that the analgesic process normally activated by HNCS can be blocked or enhanced by the verbal induction of expectations through suggestions. Changes in shock-anxiety induced by these suggestions were correlated to changes in shock-pain and RIII-reflex, but these changes did not emerge as a mediator of the association between manipulated expectations and HNCS analgesia. Overall, the results demonstrate that HNCS analgesia is modulated by expectations, either from a priori beliefs or suggestions, and this appears to be independent of anxiety processes. This study demonstrates that a priori and manipulated expectations can enhance or block HNSC analgesia. Results also suggest that expectations might influence responses to analgesic treatments by altering descending modulation and contribute to observed deficit in pain inhibition processes of chronic pain patients. |
23260451 | μ-Opioid receptor gene A118G polymorphism predicts pain recovery after sexual assault. | Pain is common after sexual assault (SA), but etiology of pain symptoms after SA is unknown. Preclinical studies suggest that the release of endogenous opioids during stress produces delayed-onset hyperalgesia. In human studies, individuals with ≥1 G allele at the μ-opioid receptor functional single nucleotide polymorphism A118G have been shown to have a reduced response to opioids. We hypothesized that if opioid-mediated hyperalgesia contributes to pain after SA, women SA survivors with 1 or more G alleles at A118G would experience reduced postassault pain. Among 52 European American women SA survivors presenting for care within 48 hours of SA, those with a G allele (12/52, 23%) experienced less severe pain (F[1,39] = 11.55, P = .002) and a reduced extent of pain (F[1,41] = 11.01, P = .002) during the 6 weeks after SA. These associations between the presence of 1 or more G alleles and reduced pain severity and reduced pain extent after SA remained significant in multivariable models controlling for age, income, education, reported pain prior to assault, and pain at the time of initial evaluation. These results suggest that endogenous opioid-mediated hyperalgesia may contribute to pain symptoms after sexual assault. Further studies examining mechanisms mediating the development of pain after sexual assault, and the potential influence of opioid-mediated hyperalgesia, are needed. |
23260450 | Fear of injury predicts self-reported and behavioral impairment in patients with chronic low back pain. | Fear of injury has been posited as crucial in pain-related anxiety and in the development of chronic pain; however, research has only measured fear of injury indirectly through other constructs (eg, fear of illness and fear of movement). The current study tested fear of injury as an independent contributor to pain-related anxiety and impairment. Patients (n = 78; 37% women) in a work-hardening treatment program for chronic low back pain completed self-report measures of pain-related anxiety, anxiety sensitivity, fear of injury, current pain, and impairment. Behavioral measures of impairment included lifting capacity, treatment outcomes, and days absent from treatment. Structural equation modeling tested the role of fear of injury within contemporary theory. Fit for the theoretical model was excellent and superior to an alternative model. Variance accounted for in pain-related anxiety by fear of injury, anxiety sensitivity, and current pain was 64%, while pain-related anxiety and current pain predicted 49% of variance in latent impairment. Fear of injury directly predicted pain-related anxiety (β = .42) and indirectly predicted impairment through pain-related anxiety (β = .19). Fear of injury may warrant theoretical and clinical consideration as an important contributor to pain-related anxiety and impairment; however, research is needed to explore how it may be causally related with other constructs. Fear of injury directly predicts pain-related anxiety and indirectly predicts self-reported and behavioral impairment. Fear of injury may warrant inclusion in contemporary theories of chronic pain. Clinicians may benefit from considering the construct in interventions for chronic pain. |
23260448 | [Correlation between demyelinating lesions and executive function decline in a sample of Mexican patients with multiple sclerosis]. | Multiple Sclerosis (MS) is characterised by several neurological symptoms including cognitive impairment, which has recently been the subject of considerable study. At present, evidence pointing to a correlation between lesion characteristics and specific cognitive impairment is not conclusive. To investigate the presence of a correlation between the characteristics of demyelinating lesions and performance of basic executive functions in a sample of MS patients. We included 21 adult patients with scores of 0 to 5 on the Kurtzke scale and no exacerbations of the disease in at least 3 months prior to the evaluation date. They completed the Stroop test and the Wisconsin Card Sorting Test (WCST). The location of the lesions was determined using magnetic resonance imaging (MRI) performed by a blinded expert in neuroimaging. Demyelinating lesions were more frequently located in the frontal and occipital lobes. The Stroop test showed that as cognitive demand increased on each of the sections in the test, reaction time and number of errors increased. On the WCST, 33.33% of patients registered as having moderate cognitive impairment. No correlation could be found between demyelinating lesion characteristics (location, size, and number) and patients' scores on the tests. Explanations of the causes of cognitive impairment in MS should examine a variety of biological, psychological, and social factors instead of focusing solely on demyelinating lesions. |
23260447 | Comparing implicit and explicit semantic access of direct and indirect word pairs in schizophrenia to evaluate models of semantic memory. | Semantic memory deficits in schizophrenia (SZ) are profound, yet there is no research comparing implicit and explicit semantic processing in the same participant sample. In the current study, both implicit and explicit priming are investigated using direct (LION-TIGER) and indirect (LION-STRIPES; where tiger is not displayed) stimuli comparing SZ to healthy controls. Based on a substantive review (Rossell and Stefanovic, 2007) and meta-analysis (Pomarol-Clotet et al., 2008), it was predicted that SZ would be associated with increased indirect priming implicitly. Further, it was predicted that SZ would be associated with abnormal indirect priming explicitly, replicating earlier work (Assaf et al., 2006). No specific hypotheses were made for implicit direct priming due to the heterogeneity of the literature. It was hypothesised that explicit direct priming would be intact based on the structured nature of this task. The pattern of results suggests (1) intact reaction time (RT) and error performance implicitly in the face of abnormal direct priming and (2) impaired RT and error performance explicitly. This pattern confirms general findings regarding implicit/explicit memory impairments in SZ whilst highlighting the unique pattern of performance specific to semantic priming. Finally, priming performance is discussed in relation to thought disorder and length of illness. |
23260446 | Histamine reduces GPIbα-mediated adhesion of platelets to TNF-α-activated vascular endothelium. | Histamine and tumor necrosis factor-α (TNF-α) are critical mediators of acute and chronic inflammation that are generated by mast cells and macrophages in atherosclerotic lesions or systemically during allergic attacks. Both of them induce activation of vascular endothelium and thus may play a role in thrombosis. Here we studied the interplay between histamine and TNF-α in glycoprotein (GP) Ibα-mediated platelet adhesion to cultured human vascular endothelial cells under static and shear flow conditions. The stimulation of endothelial cells with histamine or TNF-α increased the number of adherent or slow rolling GP Ibα-coated microbeads or washed human platelets. However, the application of histamine to endothelium pre-activated by TNF-α inhibited GP Ibα-mediated platelet adhesion. These effects were found to be associated with changes in the concentration of ultra large von Willebrand factor (ULVWF) strings anchored to endothelium. The results of this study indicate that histamine released during mast cell degranulation may cause or inhibit thrombosis, depending on whether it acts on resting endothelial cells or on cells pre-activated by other inflammatory stimuli. |
23260445 | Platelet-leukocyte crosstalk: Linking proinflammatory responses to procoagulant state. | Platelet activation is known to be associated with the release of a vast array of chemokines and proinflammatory lipids which induce pleiotropic effects on a wide variety of tissues and cells, including leukocytes. During thrombosis, the recruitment of leukocytes to activated platelets is considered an important step which not only links thrombosis to inflammatory responses but may also enhance procoagulant state. This phenomenon is highly regulated and influenced by precise mutual interactions between the cells at site of vascular injury and thrombi formation. Platelet-leukocyte interaction involves a variety of mediators including adhesion molecules, chemokines and chemoattractant molecules, shed proteins, various proinflammatory lipids and other materials. The current review addresses the detailed mechanisms underlying platelet-leukocyte crosstalk. This includes their adhesive interactions, transcellular metabolisms, induced tissue factor activity and neutrophil extracellular traps formation as well as the impacts of these phenomena in modulation of the proinflammatory and procoagulant functions in a reciprocal manner that enhances the physiological responses. |
23260443 | A review of macroscopic thrombus modeling methods. | Hemodynamics applied to mechanobiology offers powerful means to predict thrombosis, and to understand the kinetics of thrombus formation on areas of vascular damage in blood flowing through the human circulatory system. Specifically, the advances in computational processing and the progress in modeling complex biological processes with spatio-temporal multi-scale methods have the potential to shift the way in which cardiovascular diseases are diagnosed and treated. This article systematically surveys the state of the art of macroscopic computational fluid dynamics (CFD) Computational fluid dynamics techniques for modeling thrombus formation, highlighting their strengths and weaknesses. In particular, a comprehensive and systematic revision of the hemodynamics models and methods is given, and the strengths and weaknesses of those employed for studying thrombus formation are highlighted. |
23260442 | Ascending aorta aneurysm and blood group A among Iranian patients. | Ascending aortic aneurysm is a life threatening conditions leading to surgery in many cases. Demonstrating risk factors for this disease is essential for development of screening strategies for high-risk populations. Blood group although described as a potential risk factor for abdominal aortic aneurysm, has not been addressed in patients with aneurysm of the ascending aorta. Our study aimed to demonstrate the prevalence of ABO blood groups among one of the largest Iranian population with diagnosed aneurysm of the ascending aorta. A retrospective study was conducted in Tehran Heart Center in Tehran, Iran reviewing profile of 24,433 patients admitted to the cardiac surgery ward between January 2005 and February 2012 to extract data of 96 patients with confirmed diagnosis of ascending aortic aneurysm (AAA). Frequency of blood groups was determined and risk factors and AAA-related complications and mortality were compared between different blood groups. Of ninety six patients with AAA, 38 patients (39.58%) had blood group A, followed by 16 patients with blood group B (16.66%), 12 blood group AB (12.5%), and 30 patients (30.25%) with blood group O. Cerebrovascular accident (CVA), peripheral vascular disease (PVD), and AAA-related mortality were more frequent in patients with blood group A. However, it did not reveal statistically significant difference (p>0.05). Our study showed that risk factors for developing vascular disease are more prevalent in patients with blood group A and this blood group is associated with higher complication and mortality in AAA. |
23260441 | Inverse association between serum lipoprotein(a) and cerebral hemorrhage in the Japanese population. | Although lipoprotein(a) (Lp(a)) is involved in cardiometabolic disease processes, the association between serum Lp(a) and stroke and/or its subtypes has not yet been elucidated among Japanese people. This study investigated the association between Lp(a) and the incidence of stroke and/or its subtypes in the general Japanese population. This population-based prospective cohort study included 10,494 community-dwelling participants (4,030 males/6,464 females). The incidence of stroke and its subtypes was the primary outcome. The subjects were divided into tertiles based on their Lp(a) levels, and the risk of all stroke and stroke subtypes was examined using Cox's proportional hazard model. A total of 393 subjects (199 males and 194 females) with stroke were identified during a follow-up duration of 10.7years. The multivariate-adjusted hazard ratios for all stroke events were 0.55 (95% confidence interval: 0.38-0.81) and 0.69 (0.49-0.99) in the 2nd (9-19mg/dl) and 3rd tertiles (≥20mg/dl) of Lp(a) in reference to the 1st tertile (<9mg/dl) in males, and 0.85 (0.59-1.24) and 0.76 (0.52-1.11) in 2nd (10-22mg/dl) and 3rd tertiles (≥23mg/dl) of Lp(a) in reference to the 1st tertile (<10mg/dl) in females. The multivariate-adjusted hazard ratios for cerebral hemorrhage were 0.26 (0.10-0.67) and 0.34 (0.15-0.76) in the 2nd and 3rd tertiles of Lp(a) in reference to the 1st tertile in males, and were 0.48 (0.23-1.04) and 0.44 (0.21-0.96) in the 2nd and 3rd tertiles of Lp(a) in females. Lp(a) was associated with the incidence of cerebral hemorrhage in the general Japanese population, particularly among males, while a similar trend was seen among females. A low Lp(a) level may be a marker of the risk of cerebral hemorrhage in this population. |
23260439 | Bioprinting for stem cell research. | Recently, there has been growing interest in applying bioprinting techniques to stem cell research. Several bioprinting methods have been developed utilizing acoustics, piezoelectricity, and lasers to deposit living cells onto receiving substrates. Using these technologies, spatially defined gradients of immobilized biomolecules can be engineered to direct stem cell differentiation into multiple subpopulations of different lineages. Stem cells can also be patterned in a high-throughput manner onto flexible implementation patches for tissue regeneration or onto substrates with the goal of accessing encapsulated stem cells of interest for genomic analysis. Here, we review recent achievements with bioprinting technologies in stem cell research, and identify future challenges and potential applications including tissue engineering and regenerative medicine, wound healing, and genomics. |
23260440 | Microalgal compounds modulate carcinogenesis in the gastrointestinal tract. | Gastrointestinal cancers rank second in overall cancer-related deaths. Carotenoids, sulfated polysaccharides, and polyunsaturated fatty acids (PUFAs) from microalgae exhibit cancer chemopreventive features at different stages of carcinogenesis. For instance, sulfated polysaccharides bear a prophylactic potential via blocking adhesion of pathogens to the gastric surface, whereas carotenoids are effective against Helicobacter pylori infection. This effect is notable because H. pylori has been targeted as the primary cause of gastric cancer. Recent results on antitumor and antibacterial compounds synthesized by microalgae are reviewed here, with an emphasis on their impact upon H. pylori infection and derived pathologies accompanying the progression of gastric carcinogenesis. |
23260438 | Outcomes after thoracoabdominal aortic aneurysm repair using hypothermic circulatory arrest. | To evaluate our experience with thoracoabdominal aortic aneurysm repair using cardiopulmonary bypass and hypothermic circulatory arrest. A total of 243 patients underwent thoracoabdominal aortic aneurysm repair with full cardiopulmonary bypass and hypothermic circulatory arrest. The degree of repair was Crawford extent I in 63 (26%), Crawford extent II in 97 (40%), and Crawford extent III in 83 patients (34%). Degenerative aneurysms were the most frequent indication for surgery, and 18 patients (7.4%) required emergency surgery. The mean duration of cardiopulmonary bypass and hypothermic circulatory arrest was 160 ± 44 and 31 ± 12 minutes, respectively. Stroke occurred in 9 patients (3.7%) and spinal cord ischemic injury in 13 patients (5.3%; 9 with paraplegia and 4 with paraparesis). Temporary dialysis for new-onset renal failure was required in 3.6% of hospital survivors. The 30-day mortality rate was 7.8% (13 patients). It was 33.3% after emergency surgery and 5.6% after elective surgery (P = .001). Spinal cord ischemic injury occurred more frequently after emergency than after elective surgery (16.7% vs 3.9%; P = .04). The overall 5-year survival was 55% and was significantly better for patients with nondegenerative aortic disease. Cardiopulmonary bypass with hypothermic circulatory arrest can be safely used for thoracoabdominal aortic aneurysm repair, providing excellent protection against end-organ injury. The early and late mortality rates did not exceed those reported for other open techniques or for endovascular repair, with particularly favorable outcomes among patients undergoing elective repair. |
23260437 | Long-term results of aortic root repair using the reimplantation technique. | Aortic valve sparing is frequently performed to treat patients with aortic root aneurysm, but there is an inadequate amount of information regarding its long-term durability. This study examines the long-term results of reimplantation of the aortic valve in patients with aortic root aneurysms. From August 1989 to December 2010, 296 consecutive patients had reimplantation of the aortic valve into a tubular Dacron graft. Their mean age was 45 years (range, 11-79 years), and 78% were men. Of the patients, 36% had Marfan syndrome and 11% had bicuspid aortic valve. Patients were followed prospectively with periodic images of the aortic root and remaining aorta. The mean follow-up was 6.9 ± 4.5 years. There were 21 patients at risk at 15 years. There were 4 operative and 18 late deaths. The survival at 5, 10, and 15 years was 95.1% ± 3.5%, 93.1% ± 4.4%, and 76.5% ± 18%, respectively. Only 3 patients required reoperation on the aortic valve; all 3 patients had the Bentall procedure. Freedom from reoperation at 5, 10, and 15 years was 99.7% ± 2.0%, 97.8% ± 5.3%, and 97.8% ± 5.3%, respectively. During follow-up, moderate aortic insufficiency developed in 9 patients, and severe aortic insufficiency developed in 2 patients. Freedom from moderate or severe aortic insufficiency at 5, 10, and 15 years was 98.3% ± 3.5%, 92.9% ± 6.5%, and 89.4% ± 12%, respectively. The function of the aortic valve implanted inside a tubular Dacron graft remains normal at 15 years in most patients after this type of aortic valve-sparing operation. |
23260436 | Principles of aortic valve repair. | During the past 15 years, important advances in the field of aortic valve repair have transformed it from an infrequent and anecdotal exercise to a feasible and attractive alternative to valve replacement in selected patients with pure aortic insufficiency. These advances include a deeper understanding of the functional anatomy of the aortic valve and pathophysiologic mechanisms of aortic insufficiency; the development of surgical techniques to restore normal geometry to the aortic root and to restore the cusp coaptation; and the development of a common terminology that can be used by all clinicians to describe the lesions, discuss repair techniques, and compare immediate and long-term outcomes after aortic valve repair. This article attempts to describe the important principles of aortic valve repair by focusing on functional anatomy, surgical techniques for cusp repair, and outcome. By analogy with mitral valve repair, we include in the term aortic valve repair not only the repair of the cusp but also the valve-sparing root replacement or any kind of functional aortic annulus stabilization. |
23260435 | Simplified frozen elephant trunk repair for acute DeBakey type I dissection. | The study objective was to describe a novel technique and assess the safety and feasibility of this initial experience for performing a modified frozen elephant trunk extended repair of acute dissection. From June 2009 to February 2012, 17 patients with DeBakey type I acute aortic dissections underwent emergency surgery using a new approach for extended repair of the ascending arch and proximal descending aorta with a hybrid technique. Fourteen patients were male (82%) with a mean age of 61.4 ± 17.5 years. Some 8 of 17 (47%) presented with malperfusion, and the mean time from symptom onset to operating room was 12.8 ± 3.7 hours. Two patients had root replacement with a stentless bioprosthesis, 1 patient had aortic valve replacement, 13 patients had the valve resuspended, and 1 patient had the native valve reimplanted as a David procedure. A single, commercially available descending thoracic stent graft (26-37 mm TAG, WL Gore and Associates, Flagstaff, Ariz) was delivered antegrade directly into the open descending aorta, trimmed proximally, and sutured into the arch of each patient. The left subclavian artery was covered in 8 of 17 patients (47%). Data were from a prospectively collected database. Follow-up computed tomography was performed at discharge, 3 months, and annually, and assessed with 3-dimensional reconstruction. There were no perioperative deaths, and all patients are still alive at intermediate follow-up. There were 2 strokes without residual deficit, and 2 patients had paraparesis postoperatively with recovery before discharge. Two patients required temporary tracheostomy for respiratory failure, and 3 patients required temporary hemodialysis. The mean length of stay was 20 ± 12 days, 10 of which were in the intensive care unit. At imaging follow-up, the proximal aortic repair was stable in all patients, and the false lumen was thrombosed in the treated segment in 87.5% of patients. A novel simplified frozen elephant trunk hybrid technique for acute type I dissections allows for safe and effective extended aortic repair with false lumen thrombosis and aortic remodeling of the treated segment. Long-term outcomes of this technique warrant further investigation. |
23260434 | Importance of false lumen thrombosis in type B aortic dissection prognosis. | Partial thrombosis of the false lumen has been reported as a significant predictor of mortality during follow-up in patients with acute type B aortic dissection. The purpose of this study was to investigate the correlation of false lumen thrombosis and aortic expansion during follow-up in patients with acute type B aortic dissection. All medically treated patients with acute type B aortic dissection observed in 4 cardiovascular referral centers between 1998 and 2011, with admission and follow-up computed tomography or magnetic resonance imaging scans, were included. Aortic diameters of the dissected aortas were measured at 4 levels on the baseline and follow-up scans, and annual growth rates were calculated. Univariate and multivariate regression analyses were used to investigate the effect of false lumen thrombosis on aortic growth rate. A total of 84 patients were included, of whom 40 (47.6%) had a partially thrombosed false lumen, 7 (8.3%) had a completely thrombosed false lumen, and 37 (44.0%) had a patent false lumen. A total of 273 of the 336 (81.3%) evaluated aortic levels were dissected segments. Overall, the mean aortic diameter increased significantly at all evaluated levels (P < .001). Univariate analysis showed that annual aortic growth rates were significantly higher in those segments having a false lumen with partial thrombosis (mean, 4.25 ± 10.2) when compared with the patent group (mean, 2.10 ± 5.56; P = .035). In multivariate analysis, partial lumen thrombosis was an independent predictor of higher aortic growth (adjusted mean difference, 2.05 mm/year; 95% confidence interval, 0.10-4.01; P = .040). In patients with acute type B aortic dissection, aortic segments with a partially thrombosed false lumen have a significantly higher annual aortic growth rate when compared with those presenting with patent or complete thrombosis of the false lumen. Therefore, patients with partial thrombosis require more intensive follow-up and may benefit from prophylactic intervention. |
23260433 | Tirone David valve-sparing aortic root replacement and cusp repair for bicuspid aortic valve disease. | The durability of valve-sparing aortic root replacement with or without cusp repair in patients with bicuspid aortic valve (BAV) disease is questioned. We analyzed the results of 75 patients with a BAV undergoing Tirone David reimplantation valve-sparing aortic root replacement. Average age was 45 ± 10 years; 80% were male; 31% had 2+ or greater aortic regurgitation (AR); annular diameter averaged 28 ± 3 mm; 32% had a Sievers' type 0 BAV, and 66% underwent concomitant cusp repair (usually cusp free margin shortening) to correct prolapse. Early (6 ± 3 days) and late (2.9 ± 1.7, 1-10 years) postoperative echocardiographic results were compared (cumulative echocardiographic follow-up, 190 patient-years; median late interval, 2 years [interquartile range, 0.68, 4.2]). Seven patients remained at risk beyond 6 years. Clinical outcome and valve function were analyzed using log-rank calculations. Actuarial survival was 99% ± 2%; freedom from reoperation was 90% ± 5%, infection 98% ± 2%, and stroke 100% at 6 years. After initial improvement in degree of AR (P < .001), minor subclinical progression of AR was observed (P > .5); however, freedom from AR of more than 2+ was 100%. Cusp free margin shortening was not associated with valve deterioration, but commissural suspensory polytetrafluoroethylene neochord creation (n = 4) portended a higher probability of recurrent AR (P = .025). After David procedure and cusp repair in patients with a BAV, midterm clinical and valve function outcomes were favorable out to 6 years. More follow-up is required to determine long-term valve durability and the hazard of other clinically important late adverse events, including eventual reoperation, to beyond 10 years. |
23260431 | Role of the hypothalamic arcuate nucleus in cardiovascular regulation. | Recently the hypothalamic arcuate nucleus (Arc) has been implicated in cardiovascular regulation. Both pressor and depressor responses can be elicited by the chemical stimulation of the Arc. The direction of cardiovascular responses (increase or decrease) elicited from the Arc depends on the baseline blood pressure. The pressor responses are mediated via increase in sympathetic nerve activity and involve activation of the spinal ionotropic glutamate receptors. Arc-stimulation elicits tachycardic responses which are mediated via inhibition of vagal input and excitation of sympathetic input to the heart. The pathways within the brain mediating the pressor and tachycardic responses elicited from the Arc have not been delineated. The depressor responses to the Arc-stimulation are mediated via the hypothalamic paraventricular nucleus (PVN). Gamma aminobutyric acid type A receptors, neuropeptide Y1 receptors, and opiate receptors in the PVN mediate the depressor responses elicited from the Arc. Some circulating hormones (e.g., leptin and insulin) may reach the Arc via the leaky blood-brain barrier and elicit their cardiovascular effects. Although the Arc is involved in mediating the cardiovascular responses to intravenously injected angiotensin II and angiotensin-(1-12), these effects may not be due to leakage of these peptides across the blood-brain barrier in the Arc; instead, circulating angiotensins may act on neurons in the SFO and mediate cardiovascular actions via the projections of SFO neurons to the Arc. Cardiovascular responses elicited by acupuncture have been reported to be mediated by direct and indirect projections of the Arc to the RVLM. |
23260432 | Depression before and after cardiac surgery: do all patients respond the same? | To characterize the prevalence, incidence, and risk factors for depression before and after cardiac surgery. Patients awaiting nonemergent surgery (N = 436), completed the Patient Health Questionnaire-9 for depression, as well as the International Physical Activity Questionnaire short version preoperatively (Q1, n = 436) and at hospital discharge (Q2, n = 374). At baseline patients were categorized depression "naïve," "at risk," or "depressed." At each interval patients were identified as "not depressed" (Patient Health Questionnaire-9 score 0-3), "possibly depressed" (score 4-9), or "depressed" (score >9). Multivariate logistic regression analysis identified independent baseline and perioperative variables associated with depression. Depression prevalence at Q1 and Q2 was 23.6% and 37.7%, respectively (P < .001). The incidence of new depression at discharge was 29.2%. Multivariate logistic regression identified independent variables associated with depression: preoperative left ventricular ejection fraction 30% to 49% (Q1: odds ratio [OR], 1.81; 95% confidence interval [CI], 1.02-3.21; P = .042), left ventricular ejection fraction < 30% (Q1: OR, 2.81; 95% CI, 1.13-6.96; P = .026), physical inactivity (Q1: OR, 2.03; 95% CI; 1.26-3.28; P = .002), baseline at-risk group (Q2: OR, 2.16; 95% CI, 1.28-3.67; P = .004), baseline depressed group (Q2: OR, 7.46; 95% CI, 4.06-13.69; P < .0001), hospital length of stay >7 days (Q2: OR, 1.62; 95% CI, 1.03-2.55; P = .039). Depression is prevalent in one-third of cardiac surgery patients at time of discharge. It is not associated with operative or postoperative risk factors, with the exception of prolonged hospital stay >7 days. Preoperative depression or being at risk for depression, is associated with the highest risk for postoperative depression. |
23260430 | Compliance with the workplace-smoking ban in the Netherlands. | In 2004 the Dutch government instituted a workplace-smoking ban. This study focuses on differences in compliance over time and between occupational sectors, and describes the background variables. Telephone interviews were conducted with company employees across industry, public and service sectors in 2004 (n=705), 2006 (n=2201) and 2008 (n=2034). The questions concerned smoking policy, aspects of awareness and motivation to implement this ban. Compliance rates increased between 2006 (83%) and 2008 (96%) after an initial stagnation in the rate of compliance between 2004 and 2006. The increase in compliance was accompanied by a less negative attitude and an increase in confidence in one's ability to comply (self-efficacy). Differences in compliance between sectors with the highest compliance (public sector) and the lowest compliance (industry) decreased from about 20% to nearly 4%. Simultaneously, in the industry there was a stronger increase for risk perception of enforcement, social influence and self-efficacy. The initial stagnation in increase of compliance might be due to the lack of a (new) coherent package of policy measures to discourage smoking. Over the entire period there was a stronger increase in compliance in the industry sector, probably due to the intensification of enforcement activities and additional policy like legislation, which might increase awareness and social support. |
23260429 | Identification of dynamin as a septin-binding protein. | Lipid rafts (detergent-resistant low-density membrane microdomain: DRM) are signal-transducing membrane platforms. In a previous study, we showed maturation-dependent localization of septin in the DRM fraction of rat brain. Mammalian septin is composed with 13-14 isoforms and these isoforms assemble to form rod-shaped hetero-oligomeric complexes. End-to-end polymerization of these complexes results in the formation of higher order structures such as filamentous sheets or bundles of filaments that restrict the fluid-like diffusion of the membrane proteins and lipids. Considering the function of septin as the membrane scaffold, elucidation of the molecular interaction of septin in DRM could be a breakthrough to understand another role of lipid rafts. In order to identify septin-binding proteins in DRM, solubilization and fractionation of septin from DRM was attempted. Several proteins were co-fractionated with septin and LC-MS/MS analysis identified one of these proteins as dynamin and Western blotting using anti-dynamin confirmed this result. Immunoprecipitation of septin11 in a crude supernatant showed co-precipitation of dynamin and dynamin fraction prepared from brain contained several septin isoforms. Within bacterially expressed septin isoforms, septin5 and septin11 bound dynamin but septin9 did not. These results suggest that some septin isoforms participate in the dynamin-related membrane dynamics. |
23260428 | Solubility relationships in binary mixtures of hemoglobin variants Application to the "gelationrd of sickle-cell hemoglobin. | A thermodynamic treatment of solubility in binary mixtures of hemoglobin variants is presented. It is shown that the reported dependence of the minimum gelling concentration in five binary mixtures of the variants S, C(Harlem') Korle-Bu and A may be satisfactorily accounted for using the derived solubility relations together with simple models relating structure to interaction energies in the condensed phase. |
23260427 | Thermodynamic and kinetic parameters of an oligonucleotide hairpin helix. | The thermodynamics of the hairpin helix-single strand transition of A(6)C(6)U(6) has been analyzed by a staggering zipper model with consideration of single strand stacking. This analysis yields an enthalpy change of +11 kcal/mole for the formation of a first, isolated base pair. The stability constant of a first (intramolecular) base pair in A(6)C(6)U(6) is around 2 × 1O(-5) at 25°C, whereas a first (intermoleciilar) base pair in an A(6) · U(6) helix is characterised by a stability constant of about 4 × 10(-3)M(-1) (25°C, extrapolated from A(n) · V(n) oligomer measurements). These data indicate a destabilizing effect of the C(6) loop. The rate constant of hairpin helix formation is 2 to 3 × 10(4) sec(-1) associated with an activation enthalpy of +2.5 kcal/mote. The rate of helix dissociation of the A(6)C(6)U(6) hairpin is in the range of 10(3) to lO(5) sec(-1) with an activation enthalpy of 21 kcal mole . A comparison with the kinetic parameters obtained for A · U oligomer helices shows a specific influence of the C(6) loop due to the stacking tendency of the cytosine residues. This intluence is preferentially reflected in the relatively low value of the rate constant of helix formation. |
23260426 | Heats of dilution of polyacrylic acid at various degrees of ionization. | The heats of dilution of polyacrylic acid at four constant degrees of ionization (α = 0, 0.25, 0.50, and 1.00) have been measured in the concentration range 0.6-0.002 monomolal. The heat of dilution for pure acid (α = 0) is positive in the investigated concentration range, whereas it is negative for partially neutralized acid (α = 0.25 and 0.50). For completely neutralized add, for sodium polyacrylate (α = 1), the measured heat effects are exothermic at concentrations above about 0.05 monomolal. while below 0.05 M they become endothermic. The experimental results have been evaluated with the help of a previously developed theoretical treatment based on the cell model. |
23260425 | Ultrasonic study of the kinetics of counterion site binding in aqueous solutions of polyelectrolytes. | The excess ultrasonic absorption due to counterion binding has been studied as a function of frequency for a series of polysalts in the range 1-150 MHz. All the relaxation spectra can be represented by a relaxation equation with two relaxation terms. The relaxation frequencies appear concentration independent and the relaxation amplitudes seem proportional to concentration. The low frequency relaxation process appears to depend mainly on the nature of the counterion while the high frequency relaxation process seems to be mostly dependent on the nature of the polyion. These results are quite similar to those obtained in ultrasonic studies of ion-pairing in solutions of divalent sulfates. The kinetic model used for the quantitative analysis of these results has been modified for polysalts through introducing the concept of"counterion condensation". In this modified model the excess absorption is assigned to the perturbation by the ultrasonic waves of the equilibria between the three states of hydration of ths complex formed by a counterion and that part of the polyion where it is bound. Analytical expressions of the relaxation amplitudes have been derived using classical procedures for this modified kinetic model. In the case of cobalt-polyphosphate (Co-PP), the ultrasonic data together with the results of NMR measurements on either Co(2+) or Co-PP have been used for the evaluation of the volume changes, the rate constants and the fractions of counterions in the three states of hydration involved in the binding equilibria. The volume changes obtained in this manner depend only slightly on the method of calculation and appear to be consistent with volume changes for outer-sphere and inner-sphere complex formation. These results are discussed. |
23260424 | A mechanical model for the half-of-the-sites reactivity of oligomeric enzymes. | We developed a model which is able to provide a rationalization of the half-of-the-sites reactivity of oligomeric enzymes. According to this model, a dimeric enzyme is considered as a system of two coupled oscilators, which are able to transmit energy (information) to each other via a weak elastic coupling. In such a system, the energy may fluctuate between the two coupled elements so as to accumulate in one of the two at a time, i.e., at one time a certain energy state will be present in only one of the two elements, if this energy state (protomer conformation) is relevant for the chemical reaction, the conditions of half-of-the-sites reactivity may be fulfilled. The limits, and possible generalization, of this model are discussed. |
23260423 | Heat denaturation of ribonuclease. | One of the main and, chronologically, perhaps one of the first questions in the study of globular protein heat denaturation is that of the applicability of the "all or none" principle to this process, i.e., whether the transition of globular protein from the native into the denaturated state occurs abruptly, without intermediate, thermodynamically stable forms or there are several successive transitions. Despite an intensive study of the process of denaturation this question still remains unsettled. Moreover, its actuality has greatly increased lately with the accumulation of contradictory data. |
23260422 | Studies on the structure of chemically methylated DNA. | CD and melting temperature measurements on the nature of DNA with chemically methylated guanine-rich sites indicate that the stable secondary structure of DNA depicted by Ramstein et al- involves considerable distortions resulting from decreased base-base stacking interaction. Besides that quantum chemical data gained from PPP calculations are in favor of a weaker hydrogen bonding interaction in the methylated guanine-cytosine base pair. CD measurements demonstrate that methylated DNA-regions differ from the nonmethylated helical structure, since formation of a condensed conformation as occurs in the transition from B to the C-uke structure is prevented by positively charged methylated guanine residues. An increase in helix winding angle, however, can not be excluded. Binding ability of the dyes acridine orange, phenosafranine, and the antibiotic actinomycin C is lowered for methylated DNA, while binding of proflavine is, in accordance with the results of Ramstein and Leng, slightly enhanced. The reason for the opposite behavior of proflavine is at present not fully understood. In particular changes in the binding ability with dyes could not be correlated with base specificity of complex formation. It is discussed that structural changes in DNA towards a loose conformation decrease the binding tendency for acridine orange, phenosafranine, and actinomycin C. |
23260421 | The temperature-dependent self-association of adenosine 5'triphosphate in 0.154 M NaCl. | The disodium salt of adenosine 5'triphosphate (ATP), dissolved in and dialyzed against isotonic saline, undergoes a temperature-dependent self-association. Self-association increases with decreasing temperature. The technical achievement that made these experiments possible was the development and availability of a hollow fiber dialyzer with a low molecular weight (200) cutoff. Several models were tested to describe the experimental data, and a monomer-dirner-trimer association seemed to describe the data best- Both the dimerization and trimerization were exothermic; values of the thermodynamic functions for these reactions are reported. The self-association reaction for ATP is much stronger than that observed for purine and cyridine, as well as for various nucleosides whose self-association in aqueous solutions has been studied. |
23260420 | Calorimetry of DNA-dye interactions in aqueous solution I. Proflavine and ethidium bromide. | The results of an investigation on the interaction of proflavine and of ethidium bromide with DNA (calf thymus) in dilute aqueous solution are reported. The binding of the two dyes by DNA has been studied by means of microcalorimetric and of equilibrium dialysis measurements. Data on the thermodynamics of dimerization of both proflavine and ethidium bromide in aqueous solution obtained on the basis of spectroscopic and/or calorimetric experiments are also reported. The enthalpy data show that dye-dimerization and dye "strong" interaction with DNA are energetically favourable and quite similar while only in the latter case the phenomenon is also entropy driven. This is taken as further evidence in support of the concept that "strong" interaction-of both proflavine and ethidium bromide with DNA means dye molecules intercalation into the native, double helical structure of the biopolymer. |
23260419 | Daxx is a key downstream component of receptor interacting protein kinase 3 mediating retinal ischemic cell death. | Receptor-interacting protein 3 (RIP3) has been implicated in ischemic necrosis of retinal cells. An in silico analysis followed by experimental validation identified death associated protein (Daxx) as a novel substrate of RIP3. In vitro binding studies revealed that RIP3 binds to the serine/proline/threonine-rich domain (amino acid 625-740) of Daxx. Upon ischemic insult, RIP3 phosphorylated Daxx at Ser-668 in the retinal ganglion cells, triggering nuclear export of Daxx. Depletion of RIP3 significantly inhibited nuclear export of Daxx and attenuated cell death to a great extent. Collectively, the findings of this study demonstrate that phosphorylation of Daxx by RIP3 comprises an important part of ischemic necrosis in rat retinal ganglion cells. |
23260418 | Sodium tungstate activates glycogen synthesis through a non-canonical mechanism involving G-proteins. | Tungstate treatment ameliorates experimental diabetes by increasing liver glycogen deposition through an as yet unidentified mechanism. The signalling mechanism of tungstate was studied in CHOIR cells and primary cultured hepatocytes. This compound exerted its pro-glycogenic effects through a new G-protein-dependent and Tyr-Kinase Receptor-independent mechanism. Chemical or genetic disruption of G-protein signalling prevented the activation of the Ras/ERK cascade and the downstream induction of glycogen synthesis caused by tungstate. Thus, these findings unveil a novel non-canonical signalling pathway that leads to the activation of glycogen synthesis and that could be exploited as an approach to treat diabetes. |
23260416 | The harmful effect of prolonged high-dose methylprednisolone in acute lung injury. | Although many literatures have shown that prolonged high-dose administration of corticosteroids is hazardous and not indicated to therapy acute lung injury (ALI), there is little information on the harmful effect of prolonged high-dose corticosteroids in acute lung injury. In this study, we aimed to investigate the effect of prolonged high-dose methylprednisolone (MPL) on ALI and improve knowledge regarding the appropriate use of corticosteroids in ALI. The different doses of MPL (3, 30, 180mg·kg(-1)) were given via tail vein injection 1h after the first time LPS administration and were daily administrated for 14days. Lung tissues and lavage samples were isolated for biochemical determinations and histological measurements at 12h, 7days and 14days after LPS administration. Single administration of 180mg·kg(-1) MPL decreased the lung injury score, wet-to-dry ratio, the total cell numbers and level of procollagen type III in BALF at 12h after LPS challenge. However, prolonged therapy with 180mg·kg (-1) MPL for 7days and 14days decreased the number of AMs in BALF and increased the above-mentioned indexes. These results suggested that the prolonged high-dose MPL has harmful effects to treat LPS-induced ALI in rats. |
23260415 | Rehabilitation and leucine supplementation as possible contributors to an athlete's muscle strength in the reathletization phase following anterior cruciate ligament surgery. | To determine the interest of a muscle rehabilitation program following anterior cruciate ligament reconstruction (ligamentoplasty) and the influence of leucine supplementation on the muscle strength of athletes undergoing reathletization. The authors have analyzed prospectively, in double blind, two groups of athletes (22 versus 23) who had randomly received either leucine supplementation or a placebo. Muscle strength was measured at the beginning and the end of the program In terms of thigh perimeter, isokinetic testing results, single-leg test and percentage of body fat. The reathletization program was identical in the two groups for an average of 2.7weeks. By the end of the program, both groups had increased their thigh perimeter at 10 and 15cm from the patella (respectively 1.2cm and 1.3cm, P<0.0001). Fat mass had decreased by 1.28% (P=0.017). Values of isokinetic muscle strength for the injured limb improved by 13 to 55% with highly significant differences. The leucine group generally showed more improved muscle parameters than the placebo group, with only one significant positive result with regard to thigh muscle perimeter at 10cm from the patella (P=0.009). With or without leucine, the rehabilitation program leads to improved muscle quality. Taking leucine appears to promote muscle recovery of the injured limb with regard to a single parameter (thigh muscle perimeter at 10cm from the patella), while the other parameters showed no significant improvement. A complementary study associating the recovery phase with other dietary supplements might help to optimize these preliminary results. |