RhoA/Rho kinase pathway contributes to the pathogenesis of thermal hyperalgesia in diabetic mice. Diabetic neuropathy is one of the most common complications of diabetes and causes various problems in daily life. Several investigations have noted that many factors in the spinal cord are involved in the symptoms of painful diabetic neuropathy, and there are very few effective therapeutic regimens. In the present study, we sought to elucidate the role of the RhoA/Rho kinase (ROCK) pathway in thermal hyperalgesia in diabetic mice. The intracellular localization of RhoA and the expression of eNOS were measured by western blotting. Thermal hyperalgesia was assessed by the tail-flick test and mechanical allodynia was assessed by automated von Frey filament test in streptozotocin(STZ)-induced diabetic mice. The spinal cord of STZ-treated diabetic mice showed increased membrane-bound RhoA compared to non-diabetic control. Treatment with the RhoA inhibitor exoenzyme C3, Clostridium botulinum, and the ROCK inhibitor Y27632 attenuated thermal hyperalgesia and mechanical allodynia in diabetic mice. Moreover, daily treatment with simvastatin attenuated all of those changes in diabetic mice. The expression of eNOS and NO metabolite contents in the spinal cord was decreased in diabetic mice, and these changes were normalized by treatment with simvastatin. The present results show that HMG-CoA reductase inhibitors have an inhibitory effect on thermal hyperalgesia in diabetic mice, which is mediated by an increase in NO production through the inhibition of RhoA/ROCK pathways. These results suggest that ROCK inhibitors and HMG-CoA inhibitors may be attractive compounds to relieve the symptoms of painful diabetic neuropathies.


Will vitamin D supplementation ameliorate diseases characterized by chronic inflammation and fatigue? Chronic NF-κB activation has been supposed as a key event in chronic fatigue syndrome (CFS) and many other better-defined pro-inflammatory diseases. Knowledge about the impact of deficiency vitamin D on chronic NF-κB activation could open a new disease approach. Whereas NF-κB activation leads at first to a pro-inflammatory immune response, later on a vitamin D-dependent anti-inflammatory response ensues. Binding of the active vitamin D metabolite 1,25(OH)(2)D(3) to vitamin D receptor (VDR) yields a transcription factor which represses NF-κB activation, and additionally modulates and down-regulates adaptive, but enhances innate immune responses, and improves redox balance, thus counterbalancing inflammation on multiple levels. However, this built-in late counterbalance against inflammation works only when stores of calcium and 25(OH)D(3) are abundant. Therefore a connection between lowered vitamin D-metabolism and persistent NF-κB activation, augmented nitrosative-oxidative stress, redox imbalance, chronic inflammation, and concomitant fatigue can be postulated. In order to confirm this hypothesis, randomized controlled clinical studies about the clinical effects of supplementation of calcium and vitamin D(3) would be necessary in diseases characterized by persistent NF-κB activation and chronic inflammation and fatigue.


Clinical outcomes of definitive intensity-modulated radiation therapy with fluorodeoxyglucose-positron emission tomography simulation in patients with locally advanced cervical cancer. In regard to Kidd et al. (Int J Radiat Oncol Biol Phys 2010;77:1085-1091.).


Emergence and establishment of Usutu virus infection in wild and captive avian species in and around Zurich, Switzerland--genomic and pathologic comparison to other central European outbreaks. In late summer 2006 considerable mortality in wild and captive Passeriformes and Strigiformes was observed in Zurich, Switzerland. All animals were found in a range of 2 km(2). Observed clinical signs involved depression, ruffled plumage, incoordination, seizures and peracute death. Nutritional status was generally moderate to poor in wild birds, and variable in captive animals. Necropsy showed marked splenomegaly, a mild hepatomegaly, and pulmonary hyperemia in most animals. Histopathologic lesions were very discrete and consisted mainly of neuronal necrosis, leucocytolysis in and around the brain blood vessels, and miliary liver necrosis. The diagnosis Usutu virus (USUV) infection was established by USUV-specific immunohistochemistry and reverse transcription-polymerase chain reaction. Partial nucleotide sequence comparisons revealed>99% identity between the viruses that emerged in Zurich in 2006, in Vienna in 2001, and in Budapest in 2005. Since 2008 a significantly lower mortality was observed in wild Passeriformes, but USUV infection was confirmed for the first time beyond Zurich city limits. Indoor housing and regular treatment against ectoparasites are likely to have prevented acute USUV disease in captive Strigiformes. USUV is a mosquito-borne flavivirus causing fatalities in various avian species. After the initial European outbreaks in Austria in 2001 it appears that the virus has extended its range in Central Europe and has established a transmission cycle between local bird and mosquito species. Further episodes of increased avian mortality in the forthcoming years, with impact on wild and captive bird populations, predominantly Passeriformes and Strigiformes, can be anticipated. Furthermore, the possibility of broader dispersal of USUV in Europe during the next mosquito seasons must be considered and an increased mortality in Passeriformes and Strigiformes must be expected until protective "flock immunity" is established. Collections of valuable and endangered Passeriformes and Strigiformes, especially young of the year, should therefore be housed indoors or treated against ectoparasites at acceptable intervals between July and September each year.


Higher biologically effective dose of radiotherapy is associated with improved outcomes for locally advanced non-small cell lung carcinoma treated with chemoradiation: an analysis of the Radiation Therapy Oncology Group. Patients treated with chemoradiotherapy for locally advanced non-small-cell lung carcinoma (LA-NSCLC) were analyzed for local-regional failure (LRF) and overall survival (OS) with respect to radiotherapy dose intensity. This study combined data from seven Radiation Therapy Oncology Group (RTOG) trials in which chemoradiotherapy was used for LA-NSCLC: RTOG 88-08 (chemoradiation arm only), 90-15, 91-06, 92-04, 93-09 (nonoperative arm only), 94-10, and 98-01. The radiotherapeutic biologically effective dose (BED) received by each individual patient was calculated, as was the overall treatment time-adjusted BED (tBED) using standard formulae. Heterogeneity testing was done with chi-squared statistics, and weighted pooled hazard ratio estimates were used. Cox and Fine and Gray's proportional hazard models were used for OS and LRF, respectively, to test the associations between BED and tBED adjusted for other covariates. A total of 1,356 patients were analyzed for BED (1,348 for tBED). The 2-year and 5-year OS rates were 38% and 15%, respectively. The 2-year and 5-year LRF rates were 46% and 52%, respectively. The BED (and tBED) were highly significantly associated with both OS and LRF, with or without adjustment for other covariates on multivariate analysis (p < 0.0001). A 1-Gy BED increase in radiotherapy dose intensity was statistically significantly associated with approximately 4% relative improvement in survival; this is another way of expressing the finding that the pool-adjusted hazard ratio for survival as a function of BED was 0.96. Similarly, a 1-Gy tBED increase in radiotherapy dose intensity was statistically significantly associated with approximately 3% relative improvement in local-regional control; this is another way of expressing the finding that the pool-adjusted hazard ratio as a function of tBED was 0.97. Higher radiotherapy dose intensity is associated with improved local-regional control and survival in the setting of chemoradiotherapy.


Fingermark detection on non-porous and semi-porous surfaces using NaYF4:Er,Yb up-converter particles. This article describes the first use of an anti-Stokes material, or up-converter, for the development of latent fingermarks on a range of non-porous surfaces. Anti-Stokes materials can absorb long-wavelength light and emit light at a shorter wavelength. This property is unusual in both natural and artificial materials and so fingermark detection techniques based on anti-Stokes luminescence are potentially sensitive and selective. Latent fingermarks on luminescent and non-luminescent substrates, including Australian polymer banknotes (a well-known 'difficult' surface), were developed with sodium yttrium tetrafluoride doped with erbium and ytterbium (NaYF(4):Er,Yb) by dry powder, wet powder, and cyanoacrylate staining techniques. This study illustrates the potential of up-converter phosphors for the detection of latent fingermarks.


A surgical technique for size reduction of exceedingly large tracheal stoma. After tracheostomy some patients may develop a tracheal stoma of excessive size. Effective application of tracheostomy tube is not possible in those patients. Inserted cannula for protection from aspiration or artificial ventilatory assistance becomes easily displaced in two patients with tracheal stoma of excessive size. A simple surgical technique for treatment of large symptomatic tracheal stoma is described in the present study. A complete symptomatic improvement was noted in those patients after size reduction of the stoma using a new surgical technique. Surgical size reduction could be helpful in large tracheal stoma in which tracheal tubes could not be secured from dislocation.


Mandible preserving pull-through oropharyngectomy for advanced oropharyngeal cancer: a pilot study. Through our experiences in the parapharyngeal space (PPS) surgery, we have learned that it is possible to gain wide exposure of the PPS near to the skull base with a transcervical approach alone. Thus, we presumed that if this type of transcervical approach would be combined with a transoral approach, a less invasive oropharyngectomy without mandibulotomy and lip-splitting might be feasible for the resection of advanced oropharyngeal cancer, sparing the morbidities associated with conventional mandibular swing approach or its modified procedures. We termed this method as a mandible preserving pull-through oropharyngectomy (MPPO) and evaluated its feasibility and efficacy in this pilot study. MPPO was applied for a series of 7 patients with advanced lateral and/or upper oropharyngeal cancer including 2 patients with T4 stage. Our current application of MPPO excludes tumors, which involves mandibular bone, the higher part of the medial pterygoid muscle, and the lateral pterygoid muscle. Safe and sufficient excision of tumors was feasible by MPPO avoiding morbidities associated with mandibulotomy or lip-splitting without compromising oncological outcomes. Although preliminary, our favorable outcomes indicate that MPPO might be a useful alternative to conventional mandibular swing approach or its modified procedures for selected cases with advanced oropharyngeal cancer. Further accumulation of data is encouraged.


Risk factors of thyroid tumors: role of environmental and occupational exposures to chemical pollutants. The rising incidence of thyroid cancer observed during the last few decades in most western countries is explained in large part by increasing numbers of diagnoses due to changes in medical screening practices. However, beside radiation exposure, exposure to environmental chemicals may also play a role in thyroid cancer etiology and in the increased incidence. This paper presents the main chemicals suspected to induce thyroid tumorigenesis, and epidemiological results on the association between chemical exposure and thyroid tumors. We reviewed experimental studies to identify the main chemicals possibly involved in thyroid tumorigenesis. We also reviewed the main epidemiological studies investigating the association between environmental chemical exposure and thyroid neoplasm in humans. Environmentally abundant chemicals may disrupt thyroid function and/or play a role in tumorigenesis through a variety of mechanisms. Epidemiological results provide insufficient evidence of a causal link between exposure to environmental chemicals and thyroid tumors, but raise the hypothesis of an increased risk of thyroid neoplasm for workers in the leather, wood, and paper industries, and those exposed to certain solvents and pesticides. This paper highlights the need for large epidemiological studies evaluating the exposure to various groups of environmental chemicals and its impact on the thyroid gland.


Polycythemia and elevated serum erythropoietin associated with a liver haemangioma. Secondary polycythemia is a rare condition, which is usually associated to neoplasia or chronic pulmonary disorders. A 41-year-old man man with no history of liver disease was admitted for erythrocytosis. The paraclinical investigations revealed an increased erythropoietin level in the serum and a voluminous hepatic tumor but its identification was unclear. A liver resection was performed and the histopathological examination concluded that the tumor was a giant cavernous haemangioma with extensive myxoid changes. After surgical resection of the haemangioma, normal haemoglobin and serum erythropoietin were obtained without any further treatment. Liver haemangioma must be included in rare cause of secondary polycythemia, and surgical resection of the haemangioma should be considered as the standard to induce complete remission.


Cardiac magnetic resonance imaging: infarct size is an independent predictor of mortality in patients with coronary artery disease. Cardiac magnetic resonance imaging (CMR) can accurately determine infarct size. Prior studies using indirect methods to assess infarct size have shown that patients with larger myocardial infarctions have a worse prognosis than those with smaller myocardial infarctions. This study assessed the prognostic significance of infarct size determined by CMR. Cine and contrast CMR were performed in 100 patients with coronary artery disease (CAD) undergoing routine cardiac evaluation. Infarct size was determined by planimetry. We used Cox proportional hazards regression analyses (stepwise forward selection approach) to evaluate the risk of all-cause death associated with traditional cardiovascular risk factors, symptoms of heart failure, medication use, left ventricular ejection fraction, left ventricular mass, angiographic severity of CAD and extent of infarct size determined by CMR. Ninety-one patients had evidence of myocardial infarction by CMR. Mean follow-up was 4.8±1.6 years after CMR, during which time 30 patients died. The significant multivariable predictors of all-cause mortality were extent of myocardial infarction by CMR, extent of left ventricular systolic dysfunction, symptoms of heart failure, and diabetes mellitus (P<.05). The presence of infarct greater than or equal to 24% of left ventricular mass and left ventricular ejection fraction less than or equal to 30% were the most optimal cut-off points for the prediction of death with bivariate adjusted hazard ratios of 2.11 (95% confidence interval 1.02-4.38) and 4.06 (95% confidence interval 1.73-9.54), respectively. The extent of myocardial infarction determined by CMR is an independent predictor of death in patients with CAD.


Efficient large-array k-domain parallel MRI using channel-by-channel array reduction. This article presents a method to explore the flexibility of channel reduction in k-domain parallel imaging (PI) with massive arrays to improve the computation efficiency. In PI, computation cost increases with the number of channels. For the k-domain methods requiring channel-by-channel reconstruction, this increase can be significant with massive arrays. In this article, a method for efficient k-domain PI reconstruction in large array systems is proposed. The method is based on the fact that in large arrays the channel sensitivity is localized, which allows channel reduction through channel cross correlation. The method is tested with simulated and in vivo MRI data from a 32-channel and 64-channel systems using the multicolumn multiline interpolation (MCMLI) method. Results show that the proposed algorithm can achieve similar or improved reconstruction quality with significantly reduced computation time for massive arrays with localized sensitivity.


Assessment of metabolic changes in the striatum of a MPTP-intoxicated canine model: in vivo ¹H-MRS study of an animal model for Parkinson's disease. Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of the dopaminergic neurons in the substantia nigra pars compacta, which projects to the striatum. We induced a selective loss of nigrostriatal dopamine neurons, by infusing the mitochondrial complex 1 inhibitor 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine (MPTP) into adult beagle dogs (N=5). Single voxel ¹H water suppressed magnetic resonance spectroscopy (¹H-MRS) at 3 T was used to assess the metabolic changes in the striatum of canine before and after MPTP intoxication. The metabolite spectra obtained from the striatum (voxel size: 2 cm³) showed a lower N-acetyl aspartate to total creatine (creatine+phosphocreatine) ratio after MPTP intoxication. There were no significant differences in other metabolite ratios such as glutamate+glutamine, choline-containing compounds (glycerophosphocholine+phophorylcholine and myo-inositol). Our findings indicated that ¹H-MRS is a sensitive, noninvasive measure of neural toxicity and biochemical alterations of the striatum in a canine model of PD, and further studies are needed to confirm brain metabolic changes in association with progression of MPTP-intoxication.


Management of childhood intussusception after reduction by enema. The objective of the study was to describe the utility of emergency department (ED)/outpatient management after enema reduction for childhood intussusception. A retrospective medical record review of children aged 2 months to 6 years with confirmed intussusception who underwent enema reduction in a tertiary care academic children's hospital was performed. Subjects were analyzed with respect to location of care after reduction (ED/outpatient vs inpatient) and number, timing, and outcome of recurrences. One hundred seventeen patients were diagnosed with intussusception by contrast or air enema during the 15-year study period, and 56 fulfilled our inclusion criteria. Ten patients (18%) were admitted to hospital after enema reduction. Mean length of stay was 33.7 hours in the hospitalized group and 7 hours in the ED group. Seven of the 56 patients had recurrences (12.5% recurrence rate). Two recurred while being observed in the ED (at 30 minutes and at 2 hours after reduction), 2 recurred at home (at 10 and 28 hours after reduction), and the other 3 recurred several months later. The early recurrence rate (recurring within 24 hours) was 5.3%. No patient had an adverse event (perforation, sepsis, bowel resection). Outpatient management is used for the majority of patients with intussusception at our institution after enema reduction. The early recurrence rate is low, and patients with recurrence after discharge do well without adverse outcomes. Emergency department observation of patients after enema reduction appears to be safe and should be routine for uncomplicated cases of intussusception.


An HPLC-MS/MS method for the quantitative determination of 4-hydroxy-anethole trithione in human plasma and its application to a pharmacokinetic study. A selective, rapid and sensitive method for the quantitation of 4-hydroxy-anethole trithione (ATX) in human plasma based on high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was developed and validated. Paracetamol was used as the internal standard (I.S.). After liquid-liquid extraction of 500 μL plasma with ethyl acetate, ATX and the I.S. were chromatographed on an Inertsil(®) ODS-3 column. The mobile phase was consisted of methanol-water (75:25, v/v) with a flow rate of 0.25 mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode via electrospray ionization (ESI) source. The calibration curve was linear over the range of 0.452-603 ng/mL (r(2)≥0.99) with a lower limit of quantitation (LLOQ) of 0.452 ng/mL. The intra- and inter-day precision (relative standard deviation, R.S.D.) values were below 13% and the accuracy (relative error, R.E.) was from -2.7% to -7.5% at three quality control levels. The assay herein described was successfully applied to a pharmacokinetic study of anethole trithione (ATT) tablet in healthy volunteers after oral administration.


Neurologic complication after a roller coaster ride. Neurologic complications after roller coaster rides are uncommon but potentially catastrophic. Physicians should have a high index of suspicion and prompt appropriate investigation. A 22-year-old healthy African American man presented with a 2-day history of constant occipital headache associated with vertigo, nausea, vomiting, and ambulatory dysfunction. Physical examination showed gait ataxia, slight dysmetria, and vertical nystagmus. Magnetic resonance imaging (MRI) of the brain showed early subacute ischemic infarct in the right cerebellum in the distribution of the right posterior inferior cerebellar artery. Magnetic resonance angiography of the neck showed focal dissection of the right vertebral artery at C1 through C2 level. On subsequent questioning, the patient recollected riding a roller coaster 2 weeks before the onset of symptoms. Anticoagulation with heparin was started, and the patient was bridged to oral warfarin. After a 5-day uneventful hospital course, symptoms improved and patient was discharged on oral anticoagulation. Cervicocephalic arterial dissections after roller coaster rides are rarely described in literature. The acceleration and abrupt changes of direction might lead to indirect trauma that is applied to mobile portions of the cervicocephalic arteries leading to intimal tears. Magnetic resonance angiography combined with axial T1-weighted cervical MRI is preferred because it is a high-sensitive, noninvasive test. The rationale for the use of anticoagulants or antiplatelets in patients with cervicocephalic arterial dissection is to prevent early recurrence and infarction. However, a meta-analysis failed to show significant difference in the rates of disability or death between both groups. Therefore, the decision for medical treatment should be made in a case-by-case basis.


Core biopsy of the breast lesions: review of technical problems and solutions: a pictorial review.


The contribution of attentional bias to worry: distinguishing the roles of selective engagement and disengagement. This study investigated the effect on worry of biased attentional engagement and disengagement. Variants of a novel attention modification paradigm were developed, designed to induce a group difference either in participants' tendency to selectively engage with, or disengage from, threatening meanings. An index of threat bias, reflecting relative speeding to process threat word compared to non-threat word content, confirmed that both procedures were effective in inducing differential attentional bias. Importantly, when the induced group difference in attentional bias followed the procedure designed to influence selective engagement with threat meanings, it also gave rise to a corresponding group difference in worry. This was not the case when it was induced by the procedure designed to influence selective disengagement from threat meanings. These findings suggest that facilitated attentional engagement with threat meanings may causally contribute to variability in worry.


The impact of compulsive cleaning on confidence in memory and cleanliness. Recent research has helped elucidate a potentially important mechanism by which repetitive, compulsive behavior leads to memory and perceptual distrust. Although the effects of repeated checking and perseverative staring have been investigated, no research to date has examined the impact of compulsive cleaning on cognitive confidence. This study examined the effect of repeated cleaning in a cohort of 60 non-clinical participants. Two sets of items were used--three different colored bowls, and three different colored plates. Participants either repeatedly cleaned bowls or plates, with the other set serving as a control. A range of variables was also assessed at pre-test and post-test, including the accuracy of memory for which items were cleaned, as well as confidence in memory, and confidence that the items were clean. Results demonstrated that while there was no impact on memory accuracy, participant's memory confidence for the control items improved, while memory confidence for the repeatedly cleaned items did not. There was also no impact of repeated cleaning on confidence in cleanliness of repeatedly cleaned or control items. Results expand on previous research examining repeated behavior and metacognition, and provide initial insights into differences between repeated checking and cleaning.


A better view of the temporomandibular joint: a technical note. The authors present a method of gaining access to the temporomandibular joint that improves visibility and surgical access. It should reduce operating times and improve results.


Mitochondrial DNA (mtDNA) and schizophrenia. The poorly understood aetiology of schizophrenia is known to involve a major genetic contribution even though the genetic factors remain elusive. Most genetic studies are based on Mendelian rules and focus on the nuclear genome, but current studies indicate that other genetic mechanisms are probably involved. This review focuses on mitochondrial DNA (mtDNA), a maternally inherited, 16.6-Kb molecule crucial for energy production that is implicated in numerous human traits and disorders. The aim of this review is to summarise the studies that have explored mtDNA in schizophrenia patients and those which provide evidence for its implication in this illness. Alterations in mitochondrial morphometry, brain energy metabolism, and enzymatic activity in the mitochondrial respiratory chain suggest a mitochondrial dysfunction in schizophrenia that could be related to the genetic characteristics of mtDNA. Moreover, evidence of maternal inheritance and the presence of schizophrenia symptoms in patients suffering from a mitochondrial disorder related to an mtDNA mutation suggest that mtDNA is involved in schizophrenia. The association of specific variants has been reported at the molecular level; however, additional studies are needed to determine whether the mitochondrial genome is involved in schizophrenia.


Evaluation of the quality of life of patients with maxillofacial defects after prosthodontic therapy with obturator prostheses. The purpose of this study was to investigate how patients with maxillofacial defects evaluate their quality of life after maxillectomy and prosthodontic therapy with obturator prostheses. 43 patients were included in the study (25 female, 18 male). 31 (72%) patients completed a standardized questionnaire of 143 items and then answered additional questions in a standardized interview. Global quality of life after prosthodontic therapy with obturator prostheses was 64% (±22.9) on average. Functioning of the obturator prosthesis, impairment of ingestion, speech and appearance, the extent of therapy, and the existence of pain had significant impact on the quality of life (p<0.005). Orofacial rehabilitation of patients with maxillofacial defects using obturator prostheses is an appropriate treatment modality. To improve the situation of patients prior to and after maxillectomy sufficient information about the treatment, adequate psychological care and speech therapy should be provided.


In situ green synthesis of biocompatible ginseng capped gold nanoparticles with remarkable stability. We report herein an unprecedented one-step green synthesis of gold nanoparticles (G-AuNps), using naturally occurring Korean red ginseng root (Panax ginseng C.A. Meyer) without any special reducing/capping agents. The AuNps generated through this ginseng-mediated process did not aggregate suggesting that the phytochemicals present in them serve as excellent coatings on the nanoparticles and thus, provide robust shielding from aggregations. The ginseng-generated AuNps exhibit remarkable in vitro stability in various buffers including: cysteine, histidine, saline, sodium chloride and a host of pH ranges. Furthermore, the phytochemical coatings on the G-AuNps rendered them nontoxic as demonstrated through detailed cytotoxicity assays using WST-8 counting kit, performed on normal cervical cells lines. The present study opens up a new possibility of conveniently synthesizing AuNps using natural products which will be useful in optoelectronic and biomedical applications.


Thermoresponsive poly(N-isopropyl acrylamide)-grafted polycaprolactone films with surface immobilization of collagen. Thermoresponsive poly(N-isopropylacrylamide) (P(NIPAAm))-grafted polycaprolactone (PCL) films with a suitable amount of immobilized cell-adhesive collagen were prepared to improve cell adhesion and proliferation above the lower critical solution temperature (LCST, 32°C) of P(NIPAAm) without destroying cell detachment properties at lower temperatures. Covalently tethered P(NIPAAm) brushes on PCL film surfaces were first prepared via surface-initiated atom transfer radical polymerization (ATRP). The alkyl bromide end groups of the grafted P(NIPAAm) brushes were used in nucleophilic substitution reactions for the direct coupling of collagen to produce the collagen-immobilized thermoresponsive PCL surface. At 37°C, the cell attachments on the collagen-immobilized thermoresponsive PCL surface were enhanced substantially. The attached cells could be recovered simply by lowering culture temperature. The P(NIPAAm)-grafted PCL films with immobilized collagen are potentially useful as adhesion modifiers for advanced cell culture and tissue engineering applications.


Effect of the two new calcium channel blockers mebudipine and dibudipine on vascular flow of isolated kidney of normal and diabetic rats. Calcium channel blockers (CCBs) are powerful drugs in the treatment of hypertension. These agents also preserve or improve renal function in patients with essential hypertensive renal disease or diabetic renal disease. There is increasing experimental evidence for the beneficial effects of dihydropyridine-type CCBs. In previous researches mebudipine and dibudipine two newly synthesized CCBs, improved normal rat kidney perfusion. The study was designed to investigate the effects of these new drugs on vascular flow of isolated kidney from diabetic rats comparing to nifedipine, also to test that the effects of the new DHPs and nifedipine on renal blood flow in the isolated perfused kidney might be altered in experimental diabetic rats. In this study normal and STZ-induced 6- to 7-week diabetic rats were used. Following the establishment of renal perfusion with a constant baseline pressure of 85-95mmHg, the renal vasculature was constricted by phenylephrine (PE) injection. Changes in the baseline perfusion pressure were recorded. Then DHP CCBs prepared in perfusion medium was fed to the kidney for 30min. Finally alterations in the baseline pressure arising from PE administrations in the presence of DHPs were recorded and data analyses were done. Mebudipine and dibudipine (1-10μM) were more effective in the inhibition of phenylephrine (PE)-induced perfusion pressure in isolated kidney of diabetic rats compared to nifedipine at similar concentrations. Based on the obtained EC(50) values for DHPs-induced inhibition of prefusion pressure, it is referred that lower concentrations of mebudipine and dibudipine are needed to inhibit PE-evoked increments of renal perfusion pressure in diabetic rats. Mebudipine and dibudipine have more potency in inhibiting PE-elicited perfusion pressure in isolated kidney from diabetic rats compared to normal rats.


Electrocardiogram analysis using a combination of statistical, geometric, and nonlinear heart rate variability features. The paper addresses a common and recurring problem of electrocardiogram (ECG) classification based on heart rate variability (HRV) analysis. Current understanding of the limits of HRV analysis in diagnosing different cardiac conditions is not complete. Existing research suggests that a combination of carefully selected linear and nonlinear HRV features should significantly improve the accuracy for both binary and multiclass classification problems. The primary goal of this work is to evaluate a proposed combination of HRV features. Other explored objectives are the comparison of different machine learning algorithms in the HRV analysis and the inspection of the most suitable period T between two consecutively analyzed R-R intervals for nonlinear features. We extracted 11 features from 5min of R-R interval recordings: SDNN, RMSSD, pNN20, HRV triangular index (HTI), spatial filling index (SFI), correlation dimension, central tendency measure (CTM), and four approximate entropy features (ApEn1-ApEn4). Analyzed heart conditions included normal heart rhythm, arrhythmia (any), supraventricular arrhythmia, and congestive heart failure. One hundred patient records from six online databases were analyzed, 25 for each condition. Feature vectors were extracted by a platform designed for this purpose, named ECG Chaos Extractor. The vectors were then analyzed by seven clustering and classification algorithms in the Weka system: K-means, expectation maximization (EM), C4.5 decision tree, Bayesian network, artificial neural network (ANN), support vector machines (SVM) and random forest (RF). Four-class and two-class (normal vs. abnormal) classification was performed. Relevance of particular features was evaluated using 1-Rule and C4.5 decision tree in the cases of individual features classification and classification with features' pairs. Average total classification accuracy obtained for top three classification methods in the two classes' case was: RF 99.7%, ANN 99.1%, SVM 98.9%. In the four classes' case the best results were: RF 99.6%, Bayesian network 99.4%, SVM 98.4%. The best overall method was RF. C4.5 decision tree was successful in the construction of useful classification rules for the two classes' case. EM and K-means showed comparable clustering results: around 50% for the four classes' case and around 75% for the two classes' case. HTI, pNN20, RMSSD, ApEn3, ApEn4 and SFI were shown to be the most relevant features. HTI in particular appears in most of the top-ranked pairs of features and is the best analyzed feature. The choice of the period T for nonlinear features was shown to be arbitrary. However, a combination of five different periods significantly improved classification accuracy, from 70% for a single period up to 99% for five periods. Analysis shows that the proposed combination of 11 linear and nonlinear HRV features gives high classification accuracy when nonlinear features are extracted for five periods. The features' combination was thoroughly analyzed using several machine learning algorithms. In particular, RF algorithm proved to be highly efficient and accurate in both binary and multiclass classification of HRV records. Interpretable and useful rules were obtained with C4.5 decision tree. Further work in this area should elucidate which features should be extracted for the best classification results for specific types of cardiac disorders.


Searching for optimal dose-volume constraints to reduce rectal toxicity after hypofractionated radiotherapy for prostate cancer. Late rectal toxicity is a major concern for prostate cancer patients treated with radiotherapy. Rectal dose-volume constraints, set as guidelines to reduce its incidence, vary among institutions. From a group of patients uniformly treated with hypofractionated radiotherapy, we correlated the incidence of late rectal toxicity with rectal dose-volume rectal constraints as described in three randomised trials for prostate cancer. Favourable-risk prostate cancer patients received a dose of 66 Gy in 22 fractions without hormonal therapy. Toxicity was prospectively assessed using Common Toxicity Criteria v3. The whole or part of the rectum and rectal wall were contoured as an organ at risk for all patients. The rectal constraints of the RTOG 0126, RTOG 0415 and the PROFIT trials were used to correlate with late rectal toxicity. The median follow-up time was 58 months. Late rectal toxicity was 62, 20 and 18% for grades 0, 1 and 2/3, respectively. No statistically significant correlation was found between late rectal toxicity and the rectal constraints used in the three trials. The number of patients violating the recommended constraints was similar for the group with grade 2/3 toxicity and the group without any toxicity. Analysis derived from the actual dose-volume histogram dose parameters of this group of patients did not show a relationship between dose to volume of the rectum and late rectal toxicity that could generate a guideline of dose constraints. For this group of patients, despite the use of recognised dose-volume constraint guidelines of three trials, we were unable to establish a relationship between these constraints and the late rectal toxicity registered. Further studies on the correlation of dosimetric parameters with rectal toxicity, particularly for hypofractionated regimens, are required. Non-dosimetric factors may also be involved in the risk of late rectal toxicity.


Residual postoperative tumour volume predicts outcome after high-dose radiotherapy for chordoma and chondrosarcoma of the skull base and spine. High-dose radiotherapy after surgical debulking is the treatment of choice for chordomas and chondrosarcomas. This study reviewed our outcomes, in relation to residual tumour volume and radiation dose, in order to inform our future practice. Nineteen patients referred to the Neuro-Oncology Unit at Addenbrooke's Hospital (Cambridge, UK) between 1996 and 2009 and treated with photon radiotherapy were reviewed. Seventeen of the 19 were treated with curative intent. The median follow-up was 53 months. The tumours in the study had a mean gross tumour volume (GTV) of 17.2 cm(3) (median 10.5 cm(3)) and a range of 0-76.3 cm(3). The median dose was 65Gy in 39 fractions. The 5 year cause-specific survival for radically treated patients with chordomas was 92% and the 5 year local control rate was 83%. The 5 year cause-specific survival and local control rates with chondrosarcomas were both 100%. A planning target volume (PTV) below 90 cm(3) is predictive of local control, but volumes above this are not. The GTV seems to be a better predictor of outcome: among the 17 of 19 patients treated curatively, a GTV threshold of 30 cm(3) distinguished local failures from the 15 patients with local control, with sensitivity to detect local control of 100% (95% confidence interval 78-100%), specificity 100% (95% confidence interval 16-100%) and positive predictive value 100% (95% confidence interval 78-100%). Our results show a high level of efficacy for fractionated photon radiotherapy after surgery, in keeping with other series. In addition, we found that although surgical debulking is essential, a small residual tumour volume may still be controlled with high-dose photon radiotherapy. This information may be relevant during neurosurgical planning, possibly allowing a reduction in risk of serious neurological deficits. This should encourage the further development of sophisticated photon radiotherapy, for patients unsuitable for proton therapy.


Patterns of retreatment by radiotherapy. To describe patterns of radiotherapy retreatment by cancer type in order to develop methods of modelling retreatment for better service planning and benchmarking. We examined an institutional database of all patients who received their first megavoltage radiotherapy for any type of cancer at the Liverpool and Macarthur Cancer Therapy Centres over the period 1997-2006. The database contains patient demographic data, dates, treatment sites and doses of radiotherapy. The treatment sites were entered as free text and were recoded into a limited number of sites; primary site, bone, brain, soft tissue, other and multiple, so that retreatment sites could be grouped for stratification and analysis. Multiple treatment sites that were part of a single treatment to a primary (for example, primary site and nodes) were recoded as 'primary'. The total retreatment ratio was defined as the number of episodes of radiotherapy divided by the number of cases in the cohort. In the period 1997-2006, 7853 patients had received 9859 episodes of radiotherapy, giving a total retreatment ratio of 26 per 100 patients. In total, 6524 patients (83%) received only one episode of treatment and 1329 received two or more episodes of treatment. The average number of retreatments was 0.26. The tumour type with the highest mean number of retreatments was myeloma (1.05), followed by unknown primary (0.41), lung (0.34) and melanoma (0.32). The lowest mean number of retreatments was for the brain (0.06). The median time between treatment episodes was longest for breast cancer (12.5 months), then colorectal cancer (12.3 months), head and neck cancers (9.0 months), lung cancer (3.8 months) and prostate cancer (5.9 months). The retreatment ratio for the cohort was affected by the length of follow-up and by the tumour type. The mean number of retreatments varied from 0.06 for central nervous system malignancy to 1.05 for myeloma, with an average of 0.026.


Recycling carbon fibre reinforced polymers for structural applications: technology review and market outlook. Both environmental and economic factors have driven the development of recycling routes for the increasing amount of carbon fibre reinforced polymer (CFRP) waste generated. This paper presents a review of the current status and outlook of CFRP recycling operations, focusing on state-of-the-art fibre reclamation and re-manufacturing processes, and on the commercialisation and potential applications of recycled products. It is shown that several recycling and re-manufacturing processes are reaching a mature stage, with implementations at commercial scales in operation, production of recycled CFRPs having competitive structural performances, and demonstrator components having been manufactured. The major challenges for the sound establishment of a CFRP recycling industry and the development of markets for the recyclates are summarised; the potential for introducing recycled CFRPs in structural components is discussed, and likely promising applications are investigated.


LED-based interferometric reflectance imaging sensor for quantitative dynamic monitoring of biomolecular interactions. Label-free optical biosensors have been established as proven tools for monitoring specific biomolecular interactions. However, compact and robust embodiments of such instruments have yet to be introduced in order to provide sensitive, quantitative, and high-throughput biosensing for low-cost research and clinical applications. Here we present the Interferometric Reflectance Imaging Sensor (IRIS) using an inexpensive and durable multi-color LED illumination source to monitor protein-protein and DNA-DNA interactions. We demonstrate the capability of this system to dynamically monitor antigen-antibody interactions with a noise floor of 5.2 pg/mm(2) and DNA single mismatch detection under denaturing conditions in an array format. Our experiments show that this platform has comparable sensitivity to high-end label-free biosensors at a much lower cost with the capability to be translated to field-deployable applications.


Oil extraction from Scenedesmus obliquus using a continuous microwave system--design, optimization, and quality characterization. A 1.2 kW, 2450 MHz resonant continuous microwave processing system was designed and optimized for oil extraction from green algae (Scenedesmus obliquus). Algae-water suspension (1:1 w/w) was heated to 80 and 95°C, and subjected to extraction for up to 30 min. Maximum oil yield was achieved at 95°C and 30 min. The microwave system extracted 76-77% of total recoverable oil at 20-30 min and 95°C, compared to only 43-47% for water bath control. Extraction time and temperature had significant influence (p<0.0001) on extraction yield. Oil analysis indicated that microwaves extracted oil containing higher percentages of unsaturated and essential fatty acids (indicating higher quality). This study validates for the first time the efficiency of a continuous microwave system for extraction of lipids from algae. Higher oil yields, faster extraction rates and superior oil quality demonstrate this system's feasibility for oil extraction from a variety of feedstock.


Screening and construction of Saccharomyces cerevisiae strains with improved multi-tolerance and bioethanol fermentation performance. In this study, a systemic analysis was initially performed to investigate the relationship between fermentation-related stress tolerances and ethanol yield. Based on the results obtained, two elite Saccharomyces cerevisiae strains, Z8 and Z15, with variant phenotypes were chosen to construct strains with improved multi-stress tolerance by genome shuffling in combination with optimized initial selection. After three rounds of genome shuffling, a shuffled strain, YZ1, which surpasses its parent strains in osmotic, heat, and acid tolerances, was obtained. Ethanol yields of YZ1 were 3.11%, 10.31%, and 10.55% higher than those of its parent strains under regular, increased heat, and high gravity fermentation conditions, respectively. YZ1 was applied to bioethanol production at an industrial scale. Results demonstrated that the variant phenotypes from available yeast strains could be used as parent stock for yeast breeding and that the genome shuffling approach is sufficiently powerful in combining suitable phenotypes in a single strain.


Effect of nitrogen, salt, and iron content in the growth medium and light intensity on lipid production by microalgae isolated from freshwater sources in Thailand. Four green microalgae (TRG, KB, SK, and PSU) identified as Botryococcus spp. by morphological criteria were isolated from lakes and freshwater ponds in southern Thailand. In nitrogen-rich medium the strains achieved a lipid content of 25.8%, 17.8%, 15.8% and 5.7%, respectively. A combination of nitrogen deficiency, moderately high light intensity (82.5 μE m(-2) s(-1)) and high level of iron (0.74 mM) improved lipid accumulation in TRG, KB, SK, and PSU strains up to 35.9%, 30.2%, 28.4% and 14.7%, respectively. The lipid contents and plant oil-like fatty acid composition of the microalgae suggested their potential as biodiesel feedstock.


Gasification of palm empty fruit bunch in a bubbling fluidized bed: a performance and agglomeration study. Gasification of palm empty fruit bunch (EFB) was investigated in a pilot-scale air-blown fluidized bed. The effect of bed temperature (650-1050 °C) on gasification performance was studied. To explore the potential of EFB, the gasification results were compared to that of sawdust. Results showed that maximum heating values (HHV) of 5.37 and 5.88 (MJ/Nm3), dry gas yield of 2.04 and 2.0 (Nm3/kg), carbon conversion of 93% and 85 % and cold gas efficiency of 72% and 71 % were obtained for EFB and sawdust at the temperature of 1050 °C and ER of 0.25. However, it was realized that agglomeration was the major issue in EFB gasification at high temperatures. To prevent the bed agglomeration, EFB gasification was performed at temperature of 770±20 °C while the ER was varied from 0.17 to 0.32. Maximum HHV of 4.53 was obtained at ER of 0.21 where no agglomeration was observed.


Enhanced production of ansamitocin P-3 by addition of isobutanol in fermentation of Actinosynnema pretiosum. Supply of isobutanol to enhance the production of anti-tumor agent ansamitocin P-3 (AP-3) in medium containing agro-industrial residues was investigated with analysis of gene transcription, enzyme activity, and intermediate accumulation. Under the optimal addition of isobutanol, about 4-fold improvement of AP-3 production was obtained, and the consumption of isobutanol and accumulation of isobutyrate, malonyl-CoA, and acetyl-CoA were observed. Compared to the control without isobutanol addition, activities of both isobutanol dehydrogenase and valine dehydrogenase were enhanced in isobutanol supplemented culture. Transcription level of genes in AP-3 biosynthetic and isobutyryl-CoA catabolic pathways responded to isobutanol addition in a similar way as AP-3 biosynthesis. It is concluded that isobutanol addition was an effective strategy for increasing AP-3 production via regulation of gene transcription and pools of precursors, and the information obtained might be helpful to the fermentation productivity improvement on large scale.


Modeling of the Contact-Adsorption-Regeneration (CAR) activated sludge process. Contact-Adsorption-Regeneration (CAR) process is a cost-effective system for wastewater treatment and has a potential for application in less-developed regions. To offer a better understanding of this process, a mathematical model was established on the basis of Activated Sludge Model No. 1 (ASM1) and by incorporating the adsorption and different hydrolysis processes. The model predictions were compared with the measured data in terms of effluent concentrations and removals of both chemical oxygen demand (COD) and NH(4)(+)-N. A good agreement between the predicted and measured data was observed, indicating that the model was capable of predicting the rapid adsorption, COD removal and nitrification processes in the CAR system. This work provides an experimental and theoretical basis for the application of the CAR process in less-developed regions.


Full description of copper uptake by algal biomass combining an equilibrium NICA model with a kinetic intraparticle diffusion driving force approach. In this work kinetic and equilibrium studies related to copper binding to the protonated macroalga Sargassum muticum are reported. An intraparticle-diffusion linear driving force (LDF) model has been chosen for the quantitative description of the kinetics at several initial metal concentrations. Copper intraparticle homogeneous diffusion coefficient (D(h)) obtained is in the range 0.2-0.9×10(-10) m(2) s(-1). NICA isotherm is demonstrated to constitute a substantial improvement with respect to a simpler Langmuir competitive equation. The binding parameters were chosen to provide the best simultaneous description of the equilibrium experiments. Values of log K(Cu) (4.3), n(Cu) (1) and p (0.31) in NICA isotherm, and log K(Cu) (3.5-5) in Langmuir competitive model, have been obtained. These parameters have been also used to predict the competition between copper and cadmium for binding sites. Two acids, HNO(3) and HCl, have been tested to evaluate their effectiveness to release copper from the metal-laden biomass.


Synthesis and biological evaluation of novel leonurine-SPRC conjugate as cardioprotective agents. The synthesis and biological evaluation of novel leonurine-SPRC conjugate, 3,5-dimethoxy-4-(2-amino-3-prop-2-ynylsulfanyl-propionyl)-benzoic acid 4-guanidino-butyl ester (1) is reported in this Letter. It is designed to improve the pharmacology efficiency by combining leonurine with S-propargyl-L-cysteine (SPRC), a cysteine analog, via a phenolic hydroxyl ester bond, which could be readily hydrolyzed to release bioactive leonurine and SPRC. Pharmacological evaluation has shown that 1 possesses potent cardioprotective effect against hypoxia-induced neonatal rat ventricular myocytes damage at lower molar concentration (10-fold less than leonurine required and 100-fold less than SPRC required). The mechanism is in partial related to improve hydrogen sulfide production, anti-oxidative stress and anti-apoptosis.


Design and synthesis of threading intercalators to target DNA. Threading intercalators are high affinity DNA binding agents that bind by inserting a chromophore into the duplex and locating one group in each groove. The first threading intercalators that can be conjugated to acids, sulfonic acids and peptides to target them to duplex DNA are described, based upon the well studied acridine-3- or 4-carboxamides. Cellular uptake of the parent acridine is rapid and it can be visualized in the nucleus of cells. Both the parent compounds and their conjugates maintain antitumor activity.


Time and frequency analysis of the static balance in young adults with Down syndrome. The main objective of this study is to understand the differences in equilibrium control between normal subjects and those with Down syndrome. A total of 54 subjects participated voluntarily, divided into control group and Down syndrome group. The equilibrium of the subjects was tested under two conditions: bipedal support with eyes open and closed. The signals were analyzed in a time and frequency domain. The statistical parameters selected (i.e., RMS distance, mean velocity, mean frequency and sway area) to analyze the behavior of the center of pressures (CoP) are calculated employing the result of the combination of the time series data in both directions (i.e. resultant distance). In order to calculate the frequency bands produced by the displacements of the CoP, a Fast Fourier Transform of the data was performed. The group with Down syndrome showed poorer static equilibrium control than the control group in the time domain. In the frequency domain, we found differences between the groups in the distribution of energy in the frequency bands analyzed. In addition, we observed the existence of an interaction effect of the group and the condition tested (p<0.001). These findings show that in the absence of visual information, the control group increases the energy at low frequencies, while the group with Down syndrome decreases it. Additionally, the lower amount of energy observed in this band under the 'eyes closed' condition may serve to identify abnormalities in the functioning of the vestibular apparatus of individuals with Down syndrome and/or difficulties experienced by these individuals in extracting relevant information from this route.


SATB1 gene expression and breast cancer prognosis. Recently it has been shown that the genome organizer SATB1 plays an important role in breast cancer progression and predicts a poor prognosis. However its prognostic value compared to markers as the estrogen receptor is currently unclear. The expression levels of SATB1 mRNA from Affymetrix microarray in a cohort of 2058 breast cancer samples and its prognostic impact were analyzed. There was no significant difference in disease-free survival among ER negative cancers but instead a benefit for high SATB1 expression among ER positive tumors (p = 0.042). However, even in ER positive cancer no independent prognostic value in multivariate analysis with standard parameters was observed. Thus the use of SATB1 as target or prognostic marker for breast cancer should be viewed with caution and a possible confounding effect of the estrogen receptor status of the tumor should be taken into account when analysing new markers as SATB1.


Kissing aneurysms of the distal anterior cerebral artery. Kissing aneurysms, a particular type of multiple aneurysm are rare. A kissing aneurysms was identified at the distal anterior cerebral artery (ACA) in a 59-year-old male patient diagnosed with subarachnoid hemorrhage (SAH). The use of three-dimensional intracranial CT angiograms revealed that kissing aneurysms (that is, an aneurysm with a bilateral symmetrical mirror image) were located at the distal ACA and diffuse SAH in basal, sylvian, and interhemispheric cisterns. Both conventional carotid angiograms showed that both distal ACA aneurysms were seen separately on both internal carotid angiograms. Two aneurysms were observed simultaneously on carotid compression of either side. Some particular cautions required in diagnosing and treating kissing aneurysms are discussed, together with a literature review.


Dopamine agonist-induced substance addiction: the next piece of the puzzle. Traditional antiparkinson treatment strategies strive to balance the antiparkinson effects of dopaminergic drugs with the avoidance of motor response complications. Dopamine agonists have an established role in delaying the emergence of motor response complications or reducing motor "off" periods. The recent recognition of a range of "behavioural addictions" that are linked to dopamine agonist use has highlighted the role of dopamine in brain reward function and addiction disorders in general. Dopamine agonists have now even been linked occasionally to new substance addictions. The challenge now for the Parkinsonologist is to also balance the net benefits of using dopamine agonists for their motor effects with avoiding the harm from behavioural compulsions.


Developing dual functional allosteric modulators of GABA(A) receptors. Positive modulators at benzodiazepine sites of α2- and α3-containing GABA(A) receptors are believed to be anxiolytic. Negative allosteric modulators of α5-containing GABA(A) receptors enhance cognition. By oocyte two-electrode voltage clamp and subsequent structure-activity relationship studies, we discovered cinnoline and quinoline derivatives that were both positive modulators at α2-/α3-containing GABA(A) receptors and negative modulators at α5-containing GABA(A) receptors. In addition, these compounds showed no functional activity at α1-containing GABA(A) receptors. Such dual functional modulators of GABA(A) receptors might be useful for treating comorbidity of anxiety and cognitive impairments in neurological and psychiatric illnesses.


Synthesis and structure-activity studies of benzyl ester meperidine and normeperidine derivatives as selective serotonin transporter ligands. A series of benzyl esters of meperidine and normeperidine were synthesized and evaluated for binding affinity at serotonin, dopamine and norepinephrine transporters. The 4-methoxybenzyl ester 8b and 4-nitrobenzyl ester 8c in the meperidine series and 4-methoxybenzyl ester 14a in the normeperidine series exhibited low nanomolar binding affinities at the SERT (K(i) values <2nM) and high SERT selectivity (DAT/SERT >1500 and NET/SERT >1500).


Virtual screening against nuclear factor κB (NF-κB) of a focus library: Identification of bioactive furocoumarin derivatives inhibiting NF-κB dependent biological functions involved in cystic fibrosis. In the present study, a structured-based virtual screening (VS) of differently substituted furocoumarins and analogues has been carried out against nuclear factor kappa B (NF-κB), with the objective of selecting molecules able to inhibit the binding of this transcription factor to the DNA. The focus library was developed starting from chemical structures obtained from the literature, as well as retrieving compounds from available commercial databases. A two dimensional substructure searching method based on four different chemical scaffolds was used for this purpose. Among the 10 highest-scored ligands selected from the docking studies, five commercially available molecules were investigated in biological assays. Four furocoumarin derivatives showed IC(50) values in the range of 40-100 μM in inhibiting NF-κB/DNA interactions studied by electrophoretic mobility shift assay (EMSA). Three compounds significantly inhibited NF-κB dependent biological functions (expression of IL-8) in cellular analysis based on Pseudomonas aeruginosa infection of cystic fibrosis IB3-1 cells. These findings validated the virtual screening approach here presented and reinforce the successful results of our previously computational studies aimed at the identification of molecules targeting NF-κB. The discovered novel compounds could be of relevance to identify more potent inhibitors of NF-κB dependent biological functions beneficial to control lung inflammation occurring in patients affected by cystic fibrosis.


The promoters of 3 celery salt-induced phloem-specific genes as new tools for monitoring salt stress responses. Genes induced by a progressive 3 week salt stress (final NaCl concentration 300 mM) were identified in the phloem of celery (Apium graveolens L., cv Vert d'Elne). A subtractive library was constructed and screened for salt-induced, phloem-specific genes. Work was focused on phloem due to its central role in inter-organ exchanges. Three genes were studied in more details, 2 coding for metallothioneins (AgMT2 and AgMT3) and one for a new mannitol transporter (AgMaT3). Expression of a reporter gene in transgenic Arabidopsis under control of promoter of each gene was located in the phloem. pAgMT2 has a typical phloem pattern with slight induction by salt stress. pAgMT3 and pAgMaT3 expression was induced by salt stress, except in minor veins. pAgMaT3 was highly active in stressed roots. The promoters described here could be regarded as new tools for engineering salt-resistant plants.


Identical homologs of the Galanthus nivalis agglutinin in Zea mays and Fusarium verticillioides. The structural domain corresponding to the Galanthus nivalis agglutinin (GNA) is a mannose-binding motif that was originally discovered in plants but according to recent data also occurs in other eukaryotes and prokaryotes. Transcriptome analyses revealed that Fusarium verticillioides expresses a protein (FvGLLc1) identical to a recently identified cytoplasmic/nuclear GNA-like lectin from maize (ZmGLLc). The FvGLLc1 and ZmGLLc gene sequences are nearly identical in the coding region as well as in the intron and the 5 and 3 prime untranslated regions. However, whereas the Fusarium genome contains only a single gene with an intron, both an intronless and an intron containing lectin gene can be amplified from maize DNA. Southern blot analysis confirmed the presence of this cytoplasmic GNA-like gene in the maize and rice genome. A comparative analysis of the products amplified by different PCRs using genomic DNA from Fusarium species and maize DNA samples from sterile as well as contaminated plant material strongly indicated that the GNA-like sequence found in maize grown under sterile conditions is not derived from a contaminating Fusarium species. Furthermore, using a PCR-based approach it could be demonstrated that this particular type of lectin occurs also in other plants from distant taxa and is markedly conserved.


Awake thoracoscopic bullaplasty.

Awake thoracoscopic bullaplasty. Staple excision of emphysematous bullae through general anesthesia is the standard surgical treatment of bullous emphysema. We have developed a new surgical technique entailing thoracoscopic bullaplasty performed in fully awake patients through sole epidural anesthesia. This prospective nonrandomized trial included 35 patients undergoing awake thoracoscopic bullaplasty between 2002 and 2009. Preoperative work-up included computed tomography with algorithm for quantitative measurement of the bulla volume. Outcome measures included patient's satisfaction with the anesthesia, scored into four grades (1=unsatisfactory; 4=excellent); ratio of arterial oxygen tension to fraction of inspired oxygen (PaO(2)/FiO(2)), and postoperative assessment of standard clinical measures at 6, 12, and 36 months. There were 29 men and six women with a median age of 60 years. Median volume of the bulla was 688 ml. Awake bullaplasty was successfully completed in 34 patients. Perioperatively, PaO(2)/FiAO(2) decreased significantly (analysis of variance (ANOVA), P<0.0001) though remaining satisfactory (>300 mmHg), whereas PaCO(2) increased intraoperatively (ANOVA, P<0.0001) but returned to baseline values 1h after surgery (P=0.20). There was no mortality; four patients had air leaks longer than 7 days. Mean hospital stay was 4.9 ± 2.2 days. Comparisons between pre- to 6-month changes in outcome measures showed improvements (P<0.0001) in forced expiratory volume in 1s (FEV(1)) (+0.37 l), residual volume (-1.16 l), dyspnea index (-2), and standard 6-min walk test (SMWT) (+71 m). These improvements lasted for up to 36 months and in no patient did operated bullae recur. Our study suggests that awake thoracoscopic bullaplasty was well tolerated and easily performed in the majority of the patients, and significant clinical improvements lasted for up to 36 months.


Cycloheximide-mediated superinduction of genes involves both native and foreign transcripts in rice (Oryza sativa L.). Rice seedlings subjected to heat shock show rapid and transient induction of Oshsp17.4-CI, Oshsp17.9A-CI and OsClpB-cyt/hsp100 transcripts. When the seedlings were pre-treated with protein synthesis inhibitor cycloheximide, levels of the above transcripts during heat shock were more elevated than those seen with heat shock alone. Heat stress and cycloheximide co-treatment resulted in higher transcript accumulation in comparison to cycloheximide pre-treatment followed by heat stress. In transgenic plants raised with OsClpB-cyt/hsp100 promoter driving expression of the reporter gus gene, expression of the gus transcript was subjected to similar superinduction event as was seen with native OsClpB-cyt/hsp100 transcripts in untransformed plants. Yeast cells transformed with variably-sized rice ClpB-cyt/hsp100 promoter driving expression of the lacZ reporter transcript showed that specific sequences of the promoter region may be implicated in superinduction.


Effect of psoriasis activity on VEGF and its soluble receptors concentrations in serum and plaque scales. Vascular endothelial growth factor (VEGF) demonstrating pro-angiogenic activity promote new blood vessel formation in psoriatic lesions. The aim of this study was to evaluate the serum concentrations of VEGF, its soluble receptors (sVEGF R1 and R2) and VEGF content in scales of patients with psoriasis. To analyze possible association with activity of the disease, serum and scales from plaques were collected from 59 patients with exacerbated chronic plaque-type psoriasis. Mean concentrations of VEGF and sVEGF R1 in sera of patients were respectively two and four times higher than in healthy controls. Serum VEGF and sVEGF R1, but not sVEGF R2 demonstrated significant correlation with psoriasis area and severity index (PASI). There was also significant correlation between VEGF levels in serum and scales. Serum sVEGF R1 concentration was significantly elevated even in patients with low psoriasis activity (PASI<10), whereas increase of serum VEGF became significant in patients with medium activity (PASI: 10-20). Levels of serum VEGF and sVEGF R1 were the highest in patients with PASI>20. We confirmed association of both serum and scales VEGF concentrations with degree of psoriasis activity and demonstrated predominant increase of sVEGF R1 vs. VEGF in serum of patients with low psoriasis activity.


Association of high mobility group box-1 protein levels with sepsis and outcome of severely burned patients. The study was performed to observe the systemic release and kinetics of high mobility group box-1 protein (HMGB1) in burned patients. 106 patients were included, and they were divided into three groups with different burn sizes: group I, group II and group III. Healthy volunteers served as normal controls (n=25). The peripheral blood samples were collected on postburn days (PBD) 1, 3, 7, 14, and 21. The blood samples were used to detect levels of HMGB1 in plasma by ELISA kits for human. Gene expression of HMGB1 in peripheral blood mononuclear cells was assessed by real-time quantitative PCR taking GAPDH as the internal standard. The levels of HMGB1 were significantly elevated on PBD 1-21 in patients with various burn sizes compared with normal controls, and there were obvious differences between group I and group III. The HMGB1 levels were significantly higher in septic patients than those without sepsis on PBD 7-21. Among septic patients, the HMGB1 levels in the survival group were markedly lower than those with fatal outcome on PBD 3-21. Extensive burn injury could result in significantly increased HMGB1 levels, which appears to be associated with the development of sepsis and fatal outcome of major burns.


A rat tracheal model to investigate stent-induced tissue hyperplasia: a pilot study. To evaluate the feasibility of stent placement and the formation of stent-induced tissue hyperplasia and to verify matrix metalloproteinase (MMP) expression in stent-induced tissue hyperplasia in a rat tracheal model. In a pilot study, four rats were used to verify MMP expression in stent-induced tracheal tissue hyperplasia based on zymography and Western blot analysis. In the main experiment, 12 rats were divided into two groups with different stent-mesh gap sizes (group I, 1.23 × 1.92 mm; group II, 0.80 × 1.80 mm). The stent was 4 mm in diameter and 8 mm long. Follow-up tracheogram was performed before sacrifice 3 weeks after stent placement. The gross and the microscopic findings were evaluated. Stent placement was technically successful in all rats. During follow-up, two rats (one from each group) died within 4 days after stent placement, and one stent in group II was placed outside the trachea. MMP-9 expression was significantly higher in tissue hyperplasia than in control normal tissue. The excised specimens showed tissue hyperplasia through the mesh, and all of the stents had become incorporated into the wall of the trachea. The papillary projection thickness, granulation tissue area, percentage of granulation tissue area, and degree of inflammatory cell infiltration were higher in group II than in group I, but there was no statistically significant difference. In this study, stent placement was feasible, and the formation of stent-induced tissue hyperplasia was evident in a rat tracheal model. MMP-9 overexpression was evident in the stent-induced tracheal tissue hyperplasia.


Aberrant ovarian and uterine feeding from the renal artery at the end of gestation: two cases.


Cardiovascular effects and predictability of cardiovascular collapse after repeated intravenous bolus injections of absolute ethanol in anesthetized pigs. To evaluate the effects of repeated intravenous bolus injections of absolute ethanol on cardiopulmonary hemodynamic changes and to investigate the predictability of ethanol-induced cardiovascular collapse in anesthetized pigs. Twenty pigs aged 3-6 months and weighing 28-38 kg were enrolled in the study. Absolute ethanol (0.1 mL/kg of body weight) was repeatedly injected through the inferior vena cava central to the renal vein at 10-minute intervals up to a total volume of 1.0 mL/kg. The subjects were divided into a cardiovascular collapse group and a no-collapse group according to the development or absence of cardiac collapse. Among the 20 pigs, 12 died before the final injection. Hemodynamic parameters measured immediately before the injection of absolute ethanol did not differ between the cardiovascular collapse group and the no-collapse group except that among animals with cardiovascular collapse, the injection immediately before the one causing cardiovascular collapse resulted in significant increases in the following hemodynamic parameters: mean pulmonary arterial pressure (P < .01), pulmonary vascular resistance (P = .04), and right ventricular end-diastolic volume (P = .02). No such increases were observed in the no-collapse group. Hemodynamic profiles in pigs obtained immediately before intravenous injection of absolute ethanol did not predict the subsequent occurrence of cardiovascular collapse except after the injection immediately preceding the one resulting in cardiovascular collapse. In this animal model, significant increases in select hemodynamic parameters occurred after the injection immediately preceding the one resulting in cardiovascular collapse.


Correlation between tumor perfusion and lipiodol deposition in hepatocellular carcinoma after transarterial chemoembolization. To study the correlation of tumor perfusion with lipiodol deposition in hepatocellular carcinoma (HCC) after transarterial chemoembolization with multidetector computed tomography (MDCT) perfusion imaging. MDCT perfusion imaging was performed in 24 patients with HCC 1 to 7 days before chemoembolization. The computed tomography (CT) perfusion parameters, such as hepatic arterial perfusion (HAP), hepatic portal perfusion (HPP), total liver perfusion (TLP), and hepatic arterial perfusion index (HAPI), were calculated with the slope method. The follow-up CT scans (noncontrast) were performed 4 weeks after chemoembolization to analyze lipiodol deposition. The lipiodol deposition in the tumor was classified into three grades and compared with CT perfusion parameters before chemoembolization. The HAP and TLP of tumors before chemoembolization were correlated with the grades of lipiodol deposition in tumors after chemoembolization (r = 0.768, P < .0001 and r = 0.616, P = .001, respectively). However, the HPP and HAPI of the tumors were not related to the grades of iodized oil deposition (r = 0.227, P = .286 and r = 0.111, P = .607, respectively). Higher HAP was correlated with better lipiodol deposition, and lower HAP was correlated with poorer lipiodol deposition. MDCT perfusion imaging has the potential to help select more appropriate patients with HCC for chemoembolization.


Celiac axis as the upper origin of ascending left colic artery: an unusual multidetector computed tomography finding.


Angiogenesis and current antiangiogenic strategies for the treatment of cancer. Angiogenesis is a complex process critical for embryonic development and for survival. It is also a critical player in many pathologic processes, most notably in neoplasia. The cell signaling pathways involved in angiogenesis have become key targets for drug design, with more than 2,500 clinical trials currently under way. This review summarizes the essential features of angiogenesis and discusses therapeutic strategies that have been applied to specific diseases known to be associated with perturbation of normal angiogenic control.


Evaluation of formation of granulation tissue caused by metallic stent placement in a rat urethral model. To evaluate the feasibility of metallic stent placement and the formation of granulation tissue caused by stent placement in a rat urethral model. A bare self-expanding metallic stent was inserted in the urethra under fluoroscopic guidance in 20 male Sprague-Dawley rats. Ten rats were euthanized at 4 weeks (group A), and the other 10 were euthanized at 8 weeks after stent placement (group B). Stenosis diameter, number of epithelial layers, degree of inflammatory cell infiltration, thickness of submucosal fibrosis, and percentage of granulation tissue area were assessed. Stent placement was technically successful in all rats. Urethrograms showed perforation in three rats, partial migration in three, and stone formation in four. Granulation tissue formation was observed in all rats at the stent-implanted urethra, and the average percentage of granulation tissue area accounted for 41% and 45% of the original urethral lumen area in groups A and B, respectively. Urethrograms and urethral specimens showed significantly less stenosis diameter, less thickness of submucosal fibrosis, and lower percentage of granulation tissue area in the proximal urethra than in the distal urethra in both groups (P < .05). Histologic results demonstrated significantly fewer epithelial layers in group B compared with group A (P = .028). Placement of a self-expandable metallic stent proved to be feasible in the rat urethra and an efficient approach to stimulate granulation tissue formation as a potential model for reproducing the mechanisms of restenosis.


Health-related quality of life and exercise tolerance in recipients of heart transplants and left ventricular assist devices: a prospective, comparative study. The aim of this study was to evaluate and compare health-related quality of life (HRQoL) and physical exercise tolerance in patients after heart transplantation (HTx) or implantation of a left ventricular assist device (LVAD). A prospective, comparative design was used to characterize changes over time in HRQoL (SF-36) and exercise tolerance in patients after HTx (n = 54) and during LVAD support (n = 36). Nine LVAD patients were lost for follow-up. The majority of patients in both groups were male (97%); the LVAD cohort tended to be younger (p = 0.06). HRQoL improved significantly in HTx patients in the SF-36 physical (p = 0.02), but not in the psychosocial (p = 0.27) component score during follow-up. In the LVAD group, HRQoL showed improvements for both the SF-36 physical and psychosocial component scores (both p = 0.04). Between-group comparisons revealed better HRQoL for the HTx cohort than the LVAD cohort for 2 of 8 SF-36 subscales. Age-, gender- and body mass index (BMI)-adjusted exercise tolerance (workload; VO(2max)) showed significant improvements for both HTx (p = 0.01) and LVAD (p = 0.01) patients. Adjusted maximum oxygen consumption was higher for HTx patients (p = 0.05) relative to LVAD patients at 8 ± 1 months after implant. HRQoL and exercise capacity increased in both groups over the time-course of the study. After adjusting for relevant variables, HTx patients showed a higher exercise tolerance compared with the LVAD group during follow-up. Thus, future large-scale intervention studies should emphasize the specific needs of these patient cohorts.


In-hospital delay of elective surgery for high volume procedures: the impact on infectious complications. Development of infectious complications after high volume elective surgical procedures imposes a significant clinical burden to the United States population. This study evaluated the association of in-hospital delay of elective procedures and the subsequent impact on infectious complications after coronary artery bypass graft (CABG) surgery, colon resection, and lung resection. The Nationwide Inpatient Sample was queried between 2003 and 2007, and patients who developed postoperative infectious complications were identified. Time to elective surgery in days from admission was calculated: 0, 1 day, 2 to 5 days, and 6 to 10 days. Infectious complications evaluated included pneumonia, urinary tract infections, postoperative sepsis, and surgical site infections. Chi-square, multivariable logistic regression analyses, analysis of variance, and Cochran-Armitage trend test were used. There were 87,318 CABG procedures, 46,728 colon resections, and 28,960 lung resections evaluated. Total infection rates significantly increased after elective surgery delays: CABG: 0 days, 5.73%;1 day, 6.68%; 2 to 5 days, 9.33%; 6 to 10 days,18.24%; colon resections: 0 days, 8.43 %;1 day, 11.86%; 2 to 5 days,15.79%;6 to 10 days,21.62%; and lung resections: 0 days, 10.17%;1 day, 14.53%; 2 to 5 days, 15.53%; 6 to 10 days, 20.56%, p < 0.0001 for all trends. Trends for increasing infections after delay were significant for pneumonia and sepsis for all procedures (p < 0.0001); urinary tract infections and surgical site infections significantly increased after CABG and colon resection. Age 80 years and older, female gender, black and Hispanic race or ethnicity, and comorbidities including congestive heart failure, chronic pulmonary disease, and renal failure were associated with delay in surgery. Postoperative hospital mortality after delayed procedures was also greater. Mean cost increased after all procedures with delays: CABG, from $25,164 to $42,055 (p < 0.0001); colon resections, from $13,660 to $25,307) (p < 0.0001); and lung resections, from $18,519 to $25,054 (p < 0.0001). In-hospital delay of elective surgery from the day of admission was associated with a significant increase in infectious complications and mortality. This delay was also associated with a significant increase in hospital cost. Future policy directed toward preventing in-hospital delay of elective surgery may offer significant cost savings and decrease infectious complications after elective surgery.


Polymorphonuclear cell priming associated with NF-kB activation in patients with severe injury is partially dependent on macrophage migration inhibitory factor. Severe trauma may induce alternations of cytokine response and polymorphonuclear cell (PMN) activity in patients. This study investigated the correlation of plasma migration inhibitory factor (MIF) level and PMN activation after severe injury, and their relationship with clinical outcomes. A prospective observational study was performed at the emergency department and intensive care unit of a university hospital. Thirty-two severe blunt trauma patients (Injury Severity Score greater than 16) with systemic inflammatory response syndrome (SIRS) were enrolled. Age- and gender-matched healthy persons were the controls. Patient blood samples were obtained within 24 hours of and at 72 hours after injury. PMNs were isolated and measured for NF-kBp65 translocation and respiratory burst. Plasma MIF, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8, and IL-10 concentrations were measured. Control PMNs were incubated with patient plasma preincubated with anti-MIF antibody or anti-IL-6 antibody; cytokine blockade effects were evaluated. Twelve patients developed organ failure. Compared with patients without organ failure, patients with organ failure had lower blood pressure and a higher base deficit on admission, higher NF-kBp65 translocation and respiratory burst of PMNs, and higher plasma MIF (968 ± 246 pg/mL vs 564 ± 299 pg/mL) and IL-6 (202 ± 91 pg/mL vs 119 ± 84 pg/mL) levels within 24 hours after injury. Plasma MIF had significant positive correlation with NF-kB translocation of PMNs within 24 hours of incurring trauma (R = 0.668). The presence of anti-MIF antibody in patients' plasma obtained within 24 hours, but not at 72 hours, after injury could significantly partially block the NF-kBp65 translocation and respiratory activity of PMNs in the controls. An early increase of plasma MIF associates with NF-kB translocation and respiratory burst in PMNs of severe trauma patients and correlates with higher morbidity. MIF is one of the important factors responsible for early PMN activation and may provide a target of immunomodulation after injury.


Persistence of antibodies to the topical hemostat bovine thrombin. Immunoassays that detect antibovine thrombin product antibodies are not widely available. However, knowing whether these antibodies are present preoperatively would be useful because re-exposure to bovine thrombin-containing products is contraindicated in patients with pre-existing antiproduct antibodies due to the risk of developing immune-mediated coagulopathies. In these exploratory analyses, we characterized one aspect of immune sensitization, the persistence of circulating antibodies after exposure to bovine thrombin product. Elapsed time since a historical surgical procedure with documented or highly likely use of bovine thrombin product was determined for 204 patients enrolled in a recently completed trial. After study completion, baseline samples were assayed for antibovine thrombin product antibodies using validated immunoassays. Antibody data were sorted by time elapsed since the historical procedure. The proportion of patients with antibovine thrombin product antibodies and 95% confidence interval (CI) were determined for each 1-year period, providing an estimate for antibody persistence. Antibovine thrombin product antibodies were detected in 20.7% of patients (23 of 111; 95% CI 14.2%, 29.2%) with ≤1 year since the historical surgical procedure; 6.8% of patients (3 of 44; 95% CI 1.68%, 18.9%) with 1 to <2 years; 16.1% of patients (5 of 31; 95% CI 6.62%, 33.1%) with 2 to <3 years; and 5.6% of patients (1 of 18; 95% CI 0.00%, 27.6%) with ≥3 years since the historical procedure. The proportion of patients with antibovine thrombin product antibodies ranged from 5.6% to 20.7% across the multiyear postoperative window. Clinicians should be aware that antibodies to bovine thrombin products may persist for years after exposure.


Surgical site infection in colorectal surgery: a review of the nonpharmacologic tools of prevention.


Management of giant hemangioma of the liver: resection versus observation. Management of patients with giant hemangiomas of the liver encounters persistent controversy. Although recent case series suggest a low complication rate with nonoperative management, the classic paradigm of preventive operative resection remains. A retrospective cohort study was conducted of 492 patients with giant hepatic hemangioma (>4 cm in size) diagnosed between 1985 and 2005 at Mayo Clinic Rochester. Long-term outcomes were assessed by patient survey, with a follow-up of 11 ± 6.4 years. Of 492 patients, 289 responded to the survey. In the nonoperative group (n = 233), 20% had persistent or new onset of hemangioma-associated symptoms, including potentially life-threatening complications in 2%. In the operative group (n = 56), perioperative complications occurred in 14%, including potentially life-threatening complications in 7%. None of the operative patients had persistent or new onset of hemangioma-associated symptoms after resection of the dominant hemangioma. In group comparison, the rate of adverse events was similar (20% versus 14%; p = 0.45) with an overall low risk for potentially life-threatening complications (2% versus 7%; p = 0.07). Size of hemangiomas was not associated with adverse events in either group. Subjective health status and quality of life at follow-up were similar in both groups (p > 0.54). Clinical observation of patients with giant hemangioma of the liver has a similar rate of complications compared with operative management, but might prevent the need for invasive interventions in some patients. Clinical observation is preferred in most patients and operative treatment should be reserved for patients with severe symptoms or disease-associated complications.


Neonatal ovarian lymphangioma.

Neonatal ovarian lymphangioma. Ovarian cysts are primarily of follicular origin and ovarian lymphangioma is an extremely rare lesion. We report a case of prenatal diagnosis of unilateral ovarian cyst in which pathologic examination revealed an ovarian lymphangioma. Ovarian cystic lymphangioma should be included in the differential diagnosis of an ovarian cyst mass in neonate.


Surgical resection for locoregional esophageal cancer is underutilized in the United States. Although esophagectomy provides the highest probability of cure in patients with esophageal cancer, many candidates are never referred for surgery. We hypothesized that esophagectomy for esophageal cancer is underused, and we assessed the prevalence of resection in national, state, and local cancer data registries. Clinical stage, surgical and nonsurgical treatments, age, and race of patients with cancer of the esophagus were identified from the Surveillance, Epidemiology and End Results (SEER) registry (1988 to 2004), the Healthcare Association of NY State registry (HANYS 2007), and a single referral center (2000 to 2007). SEER identified a total of 25,306 patients with esophageal cancer (average age 65.0 years, male-to-female ratio 3:1). HANYS identified 1,012 cases of esophageal cancer (average age 67 years, M:F ratio 3:1); stage was not available from NY State registry data. A single referral center identified 385 patients (48 per year; average age 67 years, M:F 3:1). For SEER data, logistic regression was used to examine determinants of esophageal resection; variables tested included age, race, and gender. Surgical exploration was performed in 29% of the total and only 44.2% of potentially resectable patients. Esophageal resection was performed in 44% of estimated cancer patients in NY State. By comparison, 64% of patients at a specialized referral center underwent surgical exploration, 96% of whom had resection. SEER resection rates for esophageal cancer did not change between 1988 and 2004. Males were more likely to receive operative treatment. Nonwhites were less likely to undergo surgery than whites (odds ratio 0.45, p < 0.001). Surgical therapy for locoregional esophageal cancer is likely underused. Racial variations in esophagectomy are significant. Referral to specialized centers may result in an increase in patients considered for surgical therapy.


Education for life.

Education for life.


Chlamydiaceae in cattle: commensals, trigger organisms, or pathogens? Epidemiological data indicate that infection of cattle with chlamydiae such as Chlamydophila (C.) pecorum, C. abortus, C. psittaci and Chlamydia suis, is ubiquitous with mixed infections occurring frequently. The apparent lack of association between infection and clinical disease has resulted in debate as to the pathogenic significance of these organisms, and their tendency to sub-clinical and/or persistent infection presents a challenge to the study of their potential effects. However, recent evidence indicates that chlamydial infections have a substantial and quantifiable impact on livestock productivity with chronic, recurrent infections associated with pulmonary disease in calves and with infertility and sub-clinical mastitis in dairy cows. Data also suggest these infections manifest clinically when they coincide with a number of epidemiological risk factors. Future research should: (1) use relevant animal models to clarify the pathogenesis of bovine chlamydioses; (2) quantify the impact of chlamydial infection at a herd level and identify strategies for its control, including sub-unit vaccine development; and (3) evaluate the zoonotic risk of bovine chlamydial infections which will require the development of species-specific serodiagnostics.


Qualitative and quantitative ultrashort echo time (UTE) imaging of cortical bone. We describe the use of two-dimensional ultrashort echo time (2D UTE) sequences with minimum TEs of 8 μs to image and quantify cortical bone on a clinical 3T scanner. An adiabatic inversion pulse was used for long T(2) water and fat signal suppression. Adiabatic inversion prepared UTE acquisitions with varying TEs were used for T(2) measurement. Saturation recovery UTE acquisitions were used for T(1) measurement. Bone water concentration was measured with the aid of an external reference phantom. UTE techniques were evaluated on cadaveric specimens and healthy volunteers. A signal-to-noise ratio of around 30, contrast-to-noise ratio of around 27/20 between bone and muscle/fat were achieved in tibia in vivo with a nominal voxel size of 0.23 × 0.23 × 6.0 mm(3) in a scan time of 5 min. A mean T(1) of 223 ± 11 ms and mean T(2) of 390 ± 19 μs were found. Mean bone water concentrations of 23.3 ± 1.6% with UTE and 21.7 ± 1.3% with adiabatic inversion prepared UTE sequences were found in tibia in five normal volunteers. The results show that in vivo qualitative and quantitative evaluation of cortical bone is feasible with 2D UTE sequences.


Theoretical studies on the interactions of XIAP-BIR3 domain with bicyclic and tricyclic core monovalent Smac mimetics. X-linked IAP can bind caspase-9 and inhibit its activity. Mitochondrial protein Smac/DIABLO can also interact with XIAP and relieve the inhibition on caspase-9 to induce apoptosis. A series of artificial Smac mimetics have been used to mimic the Smac N-terminal tetrapeptide AVPI to bind to XIAP-BIR3, but these structural diverse mimetics exhibited distinct binding affinities. To get an insight into the binding nature and optimize the structures, molecular docking and dynamics simulations were used to study the binding of XIAP-BIR3 with three groups of Smac mimetics. The docking results reveal that these Smac mimetics anchored on the surface groove of XIAP-BIR3 and superimposed well with AVPI. The modifications on the seven-membered ring of bicyclic core segment do not strengthen the binding affinity, while a benzyl introduced to the five-membered ring is favorable to the binding. Molecular dynamics simulations on three typical systems show that these complexes are very stable. Hydrogen bonds between the bicyclic core segment and Thr308 play critical roles in maintaining the stability of complex. The binding free energies calculated by MM_PBSA method are consistent with the experimental results.


Clinical outcomes following hematopoietic stem cell transplantation for the treatment of mucopolysaccharidosis VI. Mucopolysaccharidosis VI (MPS VI, Maroteaux-Lamy Syndrome) is one of approximately 50 known lysosomal storage disorders. MPS VI is characterized by an absence or deficiency of N-acetylgalactosamine 4-sulfatase (arylsulfatase B) resulting in accumulation of dermatan sulfate. Prior to the availability of enzyme replacement therapy (ERT), the clinical management of MPS VI was limited to supportive care and allogeneic hematopoietic stem cell transplantation (HSCT); however, due to the rarity of this disease, little is known about the long-term outcomes of HSCT for MPS VI. The following retrospective study was performed using aggregate data gathered by the Center for International Blood and Marrow Transplant Research (CIBMTR) between 1982 and 2007 to determine survival probability for patients with MPS VI following allogeneic HSCT. This analysis identified 45 MPS VI patients with a median age of 5 years (range, 1-22 years) at the time they received an allogeneic HSCT. Cumulative incidence (95% CI) of acute graft-vs.-host disease at 100 days was 36% (21-53%). Probability of survival was 78% (65-89%) at 100 days and 66% (52-79%) at 1 and 3 years. While these data are based upon small numbers of recipients, they represent the largest series to date and may help clinicians assess the relative risks and benefits of currently available therapies.


Bone vascularization and remodeling.

Bone vascularization and remodeling.


Prevalence of treated diabetes: Geographical variations at the small-area level and their association with area-level characteristics. A multilevel analysis in Southeastern France. This study estimated geographical variations in the prevalence of treated diabetes (TD) at the small-area level in Southeastern France to determine whether or not the characteristics of these areas (in particular, socioeconomic status or "SES") are associated with TD independent of person-level factors. The study used drug reimbursement data for 2008 from the General Health Insurance Scheme in Southeastern France for beneficiaries aged 18 years or over. TD patients were defined as those to whom oral antidiabetic drugs or insulin had been dispensed at least three times within the year. Area (canton) characteristics associated with the prevalence of TD were studied using multilevel Poisson regression. In 2008, the crude prevalence of TD in adults in Southeastern France was 5.14%. In addition, TD prevalence was significantly higher in the more deprived and population-dense cantons independent of person-level factors (age, gender, low SES). This study found a positive association between area deprivation and TD, and adds further evidence to the scanty data so far available on this topic. This finding should contribute to pinpointing priority action areas for programmes of diabetes prevention. However, more research is needed to further elucidate the mechanism(s) linking area deprivation and diabetes.


Effect of ultrasound and temperature on tomato peroxidase. Tomato peroxidase (POD) was inactivated by heat and ultrasound. Thermal inactivation of tomato POD was performed at temperatures of 63, 64, 65, 66 and 67°C. Thermal inactivation of POD in tomato showed apparent first-order kinetics. E(a) was calculated from the slopes of Arrhenius plot and found as 14.9×10(4) J/mol. The effect of ultrasound on tomato peroxidase inactivation was investigated at 15%, 25%, 40%, 50% and 75% ultrasonic powers for 20-150 s. It was observed that as the ultrasonic power increased, inactivation rate increased. 100% POD inactivation was observed at 50% power for 150 s and at 75% power for 90 s of ultrasonication. Regeneration of POD activity was investigated for the samples exposed to ultrasound at different ultrasonic powers. It was observed that at 15% and 25% ultrasonic powers, residual enzyme activity increased linearly, whereas at powers of 40%, 50% and 75% residual enzyme activity increased nonlinearly. There was no regeneration in the samples which 100% enzyme inactivation obtained by ultrasound. A significant decrease in vitamin C content of tomato extract was observed as a function of temperature and treatment time, whereas ultrasonic treatment had no significant effect on vitamin C content of tomato extract.


Synthesis of chalcone (3-(4-fluorophenyl)-1-(4-methoxyphenyl)prop-2-en-1-one): advantage of sonochemical method over conventional method. In this work, an attempt was made to synthesize chalcone (3-(4-fluorophenyl)-1-(4-methoxyphenyl)prop-2-en-1-one) by condensation of 4-fluorobenzaldehyde with 1-(4-methoxyphenyl)ethanone under basic conditions by using both conventional (NUS) and sonochemical (US) methods. A simple condensation reaction of 4-fluorobenzaldehyde and 1-(4-methoxyphenyl)ethanone using potassium hydroxide as a base was carried out for the study. The synthesized chalcone derivative was characterized for FTIR, NMR, elemental analyses and studied for XRD, PSM, TGA and SEM properties to evaluate its performance obtained under ultrasonic energy. It was observed that complete conversion to chalcone occurred in 10 min by sonochemical method and in 4h by conventional method. Also it was found that crystallinity of the US synthesized chalcone was found to be increased by 63% than that of NUS synthesized chalcone. Finally, it has been observed that chalcone synthesis using sonochemical method is an energy efficient technique over conventional method (almost 90% of energy saving).