Endovascular management of Paget-Schroetter syndrome.
Spontaneous thrombosis of the axillary and subclavian venous segments in young, healthy adults (effort thrombosis or Paget-Schroetter syndrome) is a rare but potentially disabling affliction. The diagnosis should be suspected in any young patient presenting with unilateral arm swelling. Typically, the dominant arm is affected, and frequent, repetitive arm use is a common component of the patients' history. Although the diagnosis can often be confirmed with a venous duplex evaluation, the central location of the venous abnormality occasionally mandates cross-sectional imaging or contrast venography to confirm the diagnosis. The underlying pathophysiology of this disorder is felt to be repetitive venous trauma owing to arm motion in the narrow anatomic space between the clavicle and first rib. The treatment of Paget-Schroetter syndrome is controversial and varies according to individual, institutional, and regional preferences. In general, the trend is toward more aggressive endovascular treatment. Prompt anticoagulation is generally accepted as the minimal treatment offered. Catheter-directed thrombolysis has also acquired a prominent role in reestablishing venous patency. The importance of relieving the anatomic compression of the subclavian vein by first rib resection remains controversial, with some experts advocating surgical intervention in all affected patients, whereas others perform this procedure selectively in cases of persistent venous stenosis or ongoing symptoms. Angioplasty with or without stenting is generally discouraged in the absence of anatomic decompression but may play an adjunctive role in patients undergoing first rib resection.


[Dimensioning nursing staff: analysis of the nurse's work at the pediatric ICU of HU-USP].
The purposes of this study were to evaluate effective time of the nurse's work during the morning shift at the Pediatric ICU of HU-USP, to identify percentage of effective time of work of these nurses dedicated to direct and indirect assistance and to determine the index of productivity of the professionals doing a retrospective analysis of daily activities records. The mean of the effective time a month of these nurses' work corresponded to 275.5 minutes, of which 49.9% were related to indirect and 50.1% to direct assistance. According to the evaluation criterion available in the literature, the productivity index found is between satisfactory and excellent.


Models suggesting field experiments to test two hypotheses explaining successional diversity.
A simple mathematical model of competition is developed that includes two alternative mechanisms promoting successional diversity. The first underpins the competition-colonization hypothesis in which early successional species are able to persist because they colonize disturbed habitats before the arrival of late successional dominant competitors. The second underpins the niche hypothesis, in which early successional species are able to persist, even with unlimited colonization by late successional dominants, because they specialize on the resource-rich conditions typical of recently disturbed sites. We modify the widely studied competition-colonization model so that it also includes the mechanism behind the niche hypothesis. Analysis of this model suggests simple experiments that determine whether the successional diversity of a field system is maintained primarily by the competition-colonization mechanism, primarily by the niche mechanism, by neither, or by both. We develop quantitative metrics of the relative importance of the two mechanisms. We also discuss the implications for the management of biodiversity in communities structured by the two mechanisms.


Antigenic properties and population stability of a foot-and-mouth disease virus with an altered Arg-Gly-Asp receptor-recognition motif.
The antigenic properties and genetic stability of a multiply passaged foot-and-mouth disease virus (FMDV) clone C-S8c1 with an Arg-Gly-Gly triplet (RGG) instead of the Arg-Gly-Asp (RGD) integrin-recognition motif at positions 141 to 143 of capsid protein VP1 are described. Clear antigenic differences between FMDV RGG and clone C-S8c1 have been documented in ELISA, enzyme-linked immunoelectrotransfer (Western) blot and neutralization assays using site A-specific monoclonal antibodies and anti-FMDV polyclonal antibodies from swine and guinea pigs. The results validate with a live virus the role of the RGD (in particular Asp-143) in recognition of (and neutralization by) antibodies, a role previously suggested by immunochemical and structural studies with synthetic peptides. The FMDV RGG was genetically stable in a large proportion of serial infections of BHK-21 cells. However, a revertant virus with RGD was generated in one out of six passage series. Interestingly, this revertant FMDV did not reach dominance but established an equilibrium with its parental FMDV RGG, accompanied by an increase of quasispecies complexity at the sequences around the RGG triplet. FMDV RGG exhibited a selective disadvantage relative to other RGD-containing clones isolated from the same parental FMDV population. The results suggest that large antigenic variations can be prompted by replacements at critical capsid sites, including those involved in receptor recognition. These critical replacements may yield viruses whose stability allows them to replicate efficiently and to expand the sequence repertoire of an antigenic site.


WITHDRAWN: Cover figures published in Cortex volume 44 (2008).
This article has been withdrawn at the request of the editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.


Hemiresection Interposition Arthroplasty of the Distal Radioulnar Joint: A Long-term Outcome Study.
Background: The aim of this study was to assess factors associated with long-term patient-reported functional, pain, and satisfaction scores in patients who underwent (Bowers) hemiresection interposition technique (HIT) arthroplasty of the distal radioulnar joint (DRUJ). The secondary aims were to determine the complication and reoperation rates. Methods: A retrospective study with long-term follow-up of patients undergoing HIT arthroplasty was performed. Demographic, disease, and treatment characteristics were collected for the 66 included patients. Thirty-one patients completed all surveys, which were the Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH), our custom-made HIT arthroplasty questionnaire, Numeric Rating Scale (NRS) for pain, and NRS for satisfaction. The mean interval between surgery and follow-up by means of questionnaires was 8.6 ± 3.4 years. Results: The mean QuickDASH score was 31.0 ± 20.2. The mean score of the HIT arthroplasty questionnaire was 2 ± 2. The median NRS for pain was 1 (interquartile range [IQR], 0-3), and the median NRS for satisfaction was 9 (IQR, 8-10). The complication rate and reoperation rate were 14% and 8%, respectively. Conclusion: Overall, patients expressed satisfaction with HIT arthroplasty, despite a mean QuickDASH score of 31.0. In our cohort, patients with inflammatory arthritis had higher satisfaction and lower pain scores. Patients who had prior trauma, prior surgery, or DRUJ subluxation are generally less satisfied. Men, older patients, and posttraumatic patients had higher long-term pain scores; however, posterior interosseous nerve neurectomy is associated with improved pain scores. Our findings support the use of HIT arthroplasty in patients with inflammatory arthritis.


Investigating Substrate Scope and Enantioselectivity of a Defluorinase by a Stereochemical Probe.
The possibility of a double Walden inversion mechanism of the fluoracetate dehalogenase FAcD (RPA1163) has been studied by subjecting rac-2-fluoro-2-phenyl acetic acid to the defluorination process. This stereochemical probe led to inversion of configuration in a kinetic resolution with an extremely high selectivity factor (E > 500), showing that the classical mechanism involving SN2 reaction by Asp110 pertains. The high preference for the (S)-substrate is of synthetic value. Wide substrate scope of RPA1163 in such hydrolytic kinetic resolutions can be expected because the reaction of the even more sterically demanding rac-2-fluoro-2-benzyl acetic acid proceeded similarly. Substrate acceptance and stereoselectivity were explained by extensive molecular modeling (MM) and molecular dynamics (MD) computations. These computations were also applied to fluoroacetic acid itself, leading to further insights.


7-Alkoxy-appended coumarin derivatives: synthesis, photo-physical properties, aggregation behaviours and current-voltage (I-V) characteristic studies on thin films.
In this study, we designed and synthesised a series of coumarin derivatives appended with a long alkoxy chain on the seventh position of the coumarin-3-carboxylate/carboxylic acid core to make thin film materials. Synthesised compounds were characterized by their UV and fluorescence spectra in solutions as well as their films prepared by both LB and spin-coated methods. The surface morphology and electrical behaviour of thin films were judged by AFM, SEM and I-V characteristic mapping respectively. Isotherm, UV-Vis absorption and fluorescence spectroscopic investigations revealed the formation of aggregates on thin films. The result of SEM and AFM images provides the information about the length and height of aggregates on the thin films of coumarin derivatives. From I-V characteristics, it was found that at room temperature, the spin-coated films of coumarin derivatives containing an ester functional group exhibited a threshold switching behaviour, whereas derivatives containing the carboxylic acid functional group showed both threshold and bipolar switching behaviours. We also noticed that the I-V characteristic features of synthesized materials depended on the length of the alkyl chain of individual series.


Skull Base Osteomyelitis: A Comprehensive Imaging Review.
Skull base osteomyelitis is a relatively rare condition, generally occurring as a complication of advanced otologic or sinus infection in immunocompromised patients. Skull base osteomyelitis is generally divided into 2 broad categories: typical and atypical. Typical skull base osteomyelitis occurs secondary to uncontrolled infection of the temporal bone region, most often from necrotizing external otitis caused by Pseudomonas aeruginosa in a patient with diabetes. Atypical skull base osteomyelitis occurs in the absence of obvious temporal bone infection or external auditory canal infection. It may be secondary to advanced sinusitis or deep face infection or might occur in the absence of a known local source of infection. Atypical skull base osteomyelitis preferentially affects the central skull base and can be caused by bacterial or fungal infections. Clinically, typical skull base osteomyelitis presents with signs and symptoms of otitis externa or other temporal bone infection. Both typical and atypical forms can produce nonspecific symptoms including headache and fever, and progress to cranial neuropathies and meningitis. Early diagnosis can be difficult both clinically and radiologically, and the diagnosis is often delayed. Radiologic evaluation plays a critical role in the diagnosis of skull base osteomyelitis, with CT and MR imaging serving complementary roles. CT best demonstrates cortical and trabecular destruction of bone. MR imaging is best for determining the overall extent of disease and best demonstrates involvement of marrow space and extraosseous soft tissue. Nuclear medicine studies can also be contributory to diagnosis and follow-up. The goal of this article was to review the basic pathophysiology, clinical findings, and key radiologic features of skull base osteomyelitis.


TGFbeta/Activin/Nodal pathway in inhibition of human embryonic stem cell differentiation by mechanical strain.
Cyclic biaxial mechanical strain has been reported to inhibit human embryonic stem cell differentiation without selecting against survival of differentiated or undifferentiated cells. We show that TGFbeta/Activin/Nodal signaling plays a crucial role in repression of human embryonic stem cell (hESC) differentiation under mechanical strain. Strain-induced transcription of TGFbeta1, Activin A, and Nodal, and upregulated Similar to Mothers Against Decapentaplegic homolog (Smad)2/3 phosphorylation in undifferentiated hESC. TGFbeta/Activin/Nodal receptor inhibitor SB431542 stimulated differentiation of hESCs cultured under biaxial strain. Exogenous addition of TGFbeta1, Activin A, or Nodal alone was insufficient to stimulate hESC self-renewal to replicate behavior of hESCs in presence of strain. However, exogenous TGFbeta1 and Activin A in combination partially replicated the self-renewing phenotype induced by strain but when combined with strain did not further stimulate self-renewal. In presence of mechanical strain, addition of a neutralizing antibody to TGFbeta1 promoted hESC differentiation whereas inhibition of Activin A by Follistatin promoted hESC differentiation to a lesser extent. Together, these findings show that TGFbeta superfamily activation of Smad2/3 is required for repression of spontaneous differentiation under strain and suggest that strain may induce autocrine or paracrine signaling through TGFbeta superfamily ligands.


Strain imaging and elasticity reconstruction of arteries based on intravascular ultrasound video images.
Based on intravascular ultrasound (IVUS) video images, a novel motion estimation method combining the genetic algorithm-based optical flow method and a step-by-step and sum strategy has been developed to estimate the displacement and strain distributions on the scan cross sections of the arteries. And then, real elasticity distributions were reconstructed under the conditions of small and large deformation. Experimental results of in vitro porcine arteries demonstrated the feasibility of the method. This investigation may have potentials to provide new technological means for monitoring and evaluating percutaneous transluminal coronary angioplasty procedure, especially, for the end users of IVUSpercimaging equipment.


Enhancing Radiology Education With Social Media.
Social media plays a significant role in many of our daily lives, both personally and professionally. This article will focus on the ways in which social media can be used to enhance radiology education today. These educational opportunities include, but are not limited to, RadDiscord, sharing interesting cases, X chats, virtual lectures, and grand rounds.


Use of the Pediatric Symptom Checklist in a low-income, Mexican American population.
To evaluate the usefulness of the Pediatric Symptom Checklist (PSC) in identifying behavioral problems in low-income, Mexican American children. A cross-sectional study design was used to examine the PSC as a screening test, with the Child Behavior Checklist (CBCL) as the criterion standard. The study was conducted at a health center in a diverse low-income community. Patients Eligible patients were children and adolescents, 4 to 16 years of age, who were seen for nonemergent, well-child care. Of 253 eligible children during a 9-month study period, 210 agreed to participate in the study. There was a 100% completion rate of the questionnaires. The average age of the children was 7.5 years, and 45% were female. Ninety-five percent of patients were of Hispanic descent (Mexican American); 86% of families spoke only Spanish. Socioeconomic status was low (more than three fourths of families earned <$20 000 annually). The CBCL Total scale determined that 27 (13%) of the children had clinical levels of behavioral problems. With a cutoff score of 24, the PSC screened 2 (1%) of the 210 children as positive for behavioral problems. Using the CBCL as the criterion standard, the PSC sensitivity was 7.4%, and the specificity was 100%. Receiver operator characteristic analysis determined that a PSC cutoff score of 12 most correctly classified children with and without behavioral problems (sensitivity, 0.74; specificity, 0.94). When using the PSC, a new cutoff score of 12 for clinical significance should be considered if screening low-income, Mexican American children for behavioral problems. Additional study is indicated to determine the causes of the PSC's apparently lower sensitivity in Mexican American populations.


The ABCD2 score: a poor predictor of stroke risk in the emergency department.
In patients presenting with transient ischemic attack in the emergency department, what is the accuracy of the ABCD2 score for predicting stroke? Perry JJ, Sharma M, Sivilotti ML, et al. Prospective validation of the ABCD2 score for patients in the emergency department with TIA. CMAJ 2011;183:1137-45. The study collaborators sought to externally validate the ABCD2 score as a tool for identifying patients seen in the emergency department with transient ischemic attack who are at high risk for stroke within 7 (primary outcome) and 90 (one of the secondary outcomes) days.


Clinical research in pediatric plastic surgery and systematic review of quality-of-life questionnaires.
In the first part of this article, examples of different research designs used to study pediatric patients who undergo plastic surgery are described. The remainder of the article discusses the measurement of outcomes in pediatric plastic surgery research, with a particular focus on the assessment of quality of life (QOL). Issues specific to measuring QOL in children are discussed (eg, developmental considerations, use of self- versus proxy report). The results of a systematic literature review to identify and appraise pediatric plastic surgery condition-specific measures of QOL are presented.


Pregnenolone rescues schizophrenia-like behavior in dopamine transporter knockout mice.
Pregnenolone belongs to a class of endogenous neurosteroids in the central nervous system (CNS), which has been suggested to enhance cognitive functions through GABA(A) receptor signaling by its metabolites. It has been shown that the level of pregnenolone is altered in certain brain areas of schizophrenic patients, and clozapine enhances pregnenolone in the CNS in rats, suggesting that pregnenolone could be used to treat certain symptoms of schizophrenia. In addition, early phase proof-of-concept clinical trials have indicated that pregnenolone is effective in reducing the negative symptoms and cognitive deficits of schizophrenia patients. Here, we evaluate the actions of pregnenolone on a mouse model for schizophrenia, the dopamine transporter knockout mouse (DAT KO). DAT KO mice mirror certain symptoms evident in patients with schizophrenia, such as the psychomotor agitation, stereotypy, deficits of prepulse inhibition and cognitive impairments. Following acute treatment, pregnenolone was found to reduce the hyperlocomotion, stereotypic bouts and pre-pulse inhibition (PPI) deficits in DAT KO mice in a dose-dependent manner. At 60 mg/kg of pregnenolone, there were no significant differences in locomotor activities and stereotypy between wild-type and DAT KO mice. Similarly, acute treatment of 60 mg/kg of pregnenolone fully rescued PPI deficits of DAT KO mice. Following chronic treatment with pregnenolone at 60 mg/kg, the cognitive deficits of DAT KO mice were rescued in the paradigms of novel object recognition test and social transmission of food preference test. Pregnenolone thus holds promise as a therapeutic candidate in schizophrenia.


Molecular mechanisms of oxidative stress-induced carcinogenesis: from epidemiology to oxygenomics.
Oxidative stress is associated with inflammation, radiation, reperfusion, and iron overload. Epidemiological observations have shown that oxidative stress is one of the major sources of carcinogenesis, the top-ranked cause of human mortality worldwide. In situations of oxidative stress, reactive oxygen and nitrogen species contribute to the alteration of genome information, presumably followed by selection of the adapted proliferating cells in a given environment. Recent data suggest that common molecular mechanisms exist in oxidative stress-induced carcinogenesis, including p16(INK4A) inactivation. Thus far, oxidative DNA damage in the genome as a cause of mutation has been recognized to be randomly distributed based on in vitro experiments, while localization of oxidative DNA damage in vivo has not been pursued. However, using a novel technique based on DNA immunoprecipitation in combination with genome information, we now know that the localization of oxidative DNA damage is not random in vivo. We propose to call this rather novel research area "oxygenomics." Many signaling pathways start from the recognition of DNA damage. Thus, possible underlying principles should be elucidated in association with each cell type, the genomic location of the damage with its transcriptional activity as well as the chromatin status determining the epigenetic effect.


Effect of different dietary proteins on plasma and liver fatty acid compositions in growing rats.
Weanling male rats were fed semipurified diets containing 20% protein derived from casein, soy protein, or wheat gluten for 5 weeks. The fat source was 2% safflower oil (containing 79.4% 18:2n-6). In comparison with the casein-fed rats, the growth rate of rats fed plant proteins was slower, particularly that of rats fed the wheat gluten diet. The plasma cholesterol levels were significantly lower in rats fed wheat gluten than in those fed the other dietary protein regimens. The fatty acid compositions of plasma and liver lipids were also examined. The ratios of 16:1/16:0, 18:1/18:0 and 20:4n-6/18:2n-6 in both plasma and liver phospholipids and cholesteryl esters were consistently reduced in animals fed plant protein suggesting a reduced activity of fatty acid desaturation. The reduction of fatty acid desaturation may possibly be attributed to the low lysine/arginine ratio in plant proteins.


Linkage disequilibrium and demographic history of wild and domestic canids.
Assessing the extent of linkage disequilibrium (LD) in natural populations of a nonmodel species has been difficult due to the lack of available genomic markers. However, with advances in genotyping and genome sequencing, genomic characterization of natural populations has become feasible. Using sequence data and SNP genotypes, we measured LD and modeled the demographic history of wild canid populations and domestic dog breeds. In 11 gray wolf populations and one coyote population, we find that the extent of LD as measured by the distance at which r2=0.2 extends <10 kb in outbred populations to >1.7 Mb in populations that have experienced significant founder events and bottlenecks. This large range in the extent of LD parallels that observed in 18 dog breeds where the r2 value varies from approximately 20 kb to >5 Mb. Furthermore, in modeling demographic history under a composite-likelihood framework, we find that two of five wild canid populations exhibit evidence of a historical population contraction. Five domestic dog breeds display evidence for a minor population contraction during domestication and a more severe contraction during breed formation. Only a 5% reduction in nucleotide diversity was observed as a result of domestication, whereas the loss of nucleotide diversity with breed formation averaged 35%.


New Method to Calculate the Angular Weighting Function for a Scattering Instrument: Application to a Dust Sensor on Mars.
Suspended dust above the Martian surface is an important element in Martian climatology. In the frame of the Exomars'22 mission, we developed a dust sensor instrument, designed to provide size parameters of dust particles suspended in Mars surface from the light scattered by the particles. Thus, to interpret the data of the dust sensor, we need a method to calculate the theoretical optical power dispersed by the particles and, therefore, the theoretical signal obtained by the instrument. This signal depends on the suspended particles and on the instrument configuration. In this paper, we present a new method to calculate the angular weighting function (Wf) for scattering sensors. Wf encompasses the scattering angles measured by the sensor and depends only on the instrument and not on the suspended particles. To calculate this Wf, we use fundamental radiometry principles and an appropriate coordinate system, where one coordinate is the scattering angle. The method is applied to the dust sensor instrument and compared with other methods. The comparison highlights the advantages of the proposed method since it avoids using an ideal sampling volume, preserves the radiometric meaning, and avoids instrument calibration. The effectiveness of the method makes it a valuable tool for the design of scattering instruments and also for the interpretation of their data.


Identification of Diabetic Small-Fiber Neuropathy Based on Electrophysiological and Psychophysical Responses to Intra-Epidermal Electric Stimulation using a Naïve Bayes Classifier.
Diagnosis and stratification of small-fiber neuropathy patients is difficult due to a lack of methods that are both sensitive and specific. Our lab recently developed a method to accurately measure psychophysical and electrophysiological responses to intra-epidermal electric stimulation, specifically targeting small nerve fibers in the skin. In this work, we study whether using one or a combination of psychophysical and electrophysiological outcome measures can be used to identify diabetic small-fiber neuropathy. It was found that classification of small-fiber neuropathy based on psychophysical and electrophysiological responses to intra-epidermal electric stimulation could match or even outperform current state-of-the-art methods for the diagnosis of small-fiber neuropathy.Clinical Relevance-Neuropathy is damage or dysfunction of nerves in the skin, often leading to the development of chronic pain. Small-fiber neuropathy is the most prevalent type of neuropathy and occurs frequently in patients with diabetes mellitus, but can also occur in other diseases or in response to chemotherapy. Early detection of neuropathy could help diabetic patients to adapt glucose management, and doctors to adjust treatment strategies to prevent nerve loss and chronic pain, but is impeded by a lack of clinical tools to monitor small nerve fiber function.


[Colocutaneous fistula after a PEG procedure with introducer technique and gastropexy].
The pull-PEG (percutaneous endoscopic gastrostomy) is the most commonly used procedure for PEG placement. Alternative methods may be used in patients with an obstructed oesophagus. We here present the case of an unusual complication during PEG placement with the new introducer technique and gastropexy. A 74-year-old men with progressive thymus cell carcinoma was referred for a PEG procedure. Since the tumour stenosis in the oesophagus was only passable with a slim-sight endoscope (5,9 mm), we decided in favour of the direct PEG method with gastropexy. The procedure was performed without any complications. 35 days later we changed the balloon catheter and were able to easily inflate the balloon. Surprisingly, the X-ray performed thereafter, revealed a misplacement of the catheter in the colon without any notable contrast medium in the stomach. Although the patient expressed no complaints, he underwent surgery on the same day proving the colocutaneous fistula. There were no signs of peritonitis. The patient's postoperative recovery was uneventful. Pull-PEG requires an intact oesophageal passage. The spread of bacteria and tumour cells is a possible risk factor. Direct punction PEG might be better in these cases. This method is not a standard procedure, but the recent implementation of an additional gastropexy represents a significant improvement. We experienced a rare complication, which was first described in 1987. However, this case is the first documented complication in association with gastropexy. This case shows that even gastropexy does not prevent colon interposition. Therefore, an endoscopic or radiological control of the tube placement after changing seems to be necessary.


Over-expression of Orai1 mediates cell proliferation and associates with poor prognosis in human non-small cell lung carcinoma.
Orai1 and STIM1 mediate calcium release-activated calcium current (CRAC) which is the best characterized store-operated calcium current involving in a wide range of cell progresses, such as cell proliferation, metastasis, apoptosis. Orai1 has been studied as a carcinogenic biomarker in some cancers such as esophageal cancer. However, its function and clinical significance in non-small cell lung cancer (NSCLC) have not been well studied. The present study was aimed at discussing the relationship between Orai1 and lung cancer malignant behavior with its clinical significance. We used quantitative real-time-PCR and Western blot to detect the expression of Orai1 in NSCLC cell lines and fresh cancer tissues. Immunohistochemistry were performed to test the location and expression of Orai1 in paraffin sections. We found that Orai1 was markedly overexpressed in both NSCLC cell lines and fresh cancer tissues. Immunohistochemistry data also revealed that overexpression of Orai1 was present in 42.4% of NSCLC tissues, compared with the corresponding adjacent nontumorous tissues. Furthermore, NSCLC patients with high Orai1 expression survived shorter than those with low Orai1 expression. In addition, when knockdown Orai1 by RNAi technic, we found the PI3k/AKT/ERK pathway was inhibited which may indicated that Orai1 could influence cell proliferation. Taken together, our study demonstrated that Orai1 was remarkably overexpressed in NSCLC and could be served as a potential prognostic marker for patients with this deadly disease.


Characterization of cardiovascular clinical events and impact of event adjudication on the treatment effect of darapladib versus placebo in patients with stable coronary heart disease: Insights from the STABILITY trial.
Clinical Endpoint Classification (CEC) in clinical trials allows FOR standardized, systematic, blinded, and unbiased adjudication of investigator-reported events. We quantified the agreement rates in the STABILITY trial on 15,828 patients with stable coronary heart disease. Investigators were instructed to report all potential events. Each reported event was reviewed independently by 2 reviewers according to prespecified processes and prespecified end point definitions. Concordance between reported and adjudicated cardiovascular (CV) events was evaluated, as well as event classification influence on final study results. In total, CEC reviewed 7,096 events: 1,064 deaths (696 CV deaths), 958 myocardial infarctions (MI), 433 strokes, 182 transient ischemic attacks, 2,052 coronary revascularizations, 1,407 hospitalizations for unstable angina, and 967 hospitalizations for heart failure. In total, 71.8% events were confirmed by CEC. Concordance was high (>80%) for cause of death and nonfatal MI and lower for hospitalization for unstable angina (25%) and heart failure (50%). For the primary outcome (composite of CV death, MI, and stroke), investigators reported 2,086 events with 82.5% confirmed by CEC. The STABILITY trial treatment effect of darapladib versus placebo on the primary outcome was consistent using investigator-reported events (hazard ratio 0.96 [95% CI 0.87-1.06]) or adjudicated events (hazard ratio 0.94 [95% CI 0.85-1.03]). The primary outcome results of the STABILITY trial were consistent whether using investigator-reported or CEC-adjudicated events. The proportion of investigator-reported events confirmed by CEC varied by type of event. These results should help improve event identification in clinical trials to optimize ascertainment and adjudication.


Exploratory analysis of plasma cytokine/chemokine levels in 6-year-old children from a birth cohort study.
This study aimed to reveal a new dimension of allergy profiles in the general population by using machine learning to explore complex relationships among various cytokines/chemokines and allergic diseases (asthma and atopic dermatitis; AD). We examined the symptoms related to asthma and AD and the plasma levels of 72 cytokines/chemokines obtained from a general population of 161 children at 6 years of age who participated in a pilot birth cohort study of the Japan Environment and Children's Study (JECS). The children whose signs and symptoms fulfilled the criteria of AD, which are mostly based on questionnaire including past symptoms, tended to have higher levels of the two chemokine ligands, CCL17 and CCL27, which are used for diagnosis of AD. On the other hand, another AD-related chemokine CCL22 level in plasma was higher only in children with visible flexural eczema, which is one of AD diagnostic criteria but was judged on the same day of blood examination unlike other criteria. Here, we also developed an innovative method of machine learning for elucidating the complex cytokine/chemokine milieu related to symptoms of allergic diseases by using clustering analysis based on the random forest dissimilarity measure that relies on artificial intelligence (AI) technique. To our surprise, the majority of children showing at least any asthma-related symptoms during the last month were divided by AI into the two clusters, either cluster-2 having elevated levels of IL-33 (related to eosinophil activation) or cluster-3 having elevated levels of CXCL7/NAP2 (related to neutrophil activation), among the total three clusters. Future studies will clarify better approach for allergic diseases by endotype classification.


Patients' views about taking a polypill to manage cardiovascular risk: a qualitative study in primary care.
A 'polypill' containing a combination of antihypertensives and statins could prevent up to 80% of cardiovascular disease (CVD) events. To investigate patients' opinions about the use of a polypill for CVD prevention. Qualitative study of 17 patients from seven primary care practices in Birmingham, UK. Patients were recruited through purposive sampling to maximise variation of characteristics. Semi-structured interviews were conducted with responders. Results were analysed and reported using a qualitative description approach. Patients expressed concerns that polypill prescription for primary prevention simply on the basis of age was unnecessary and would lead to side effects, despite recognising potential benefits. For high-risk patients, or for secondary prevention, a polypill was deemed more acceptable, but was still felt to require regular monitoring of blood pressure and cholesterol. Patients were sceptical about the role of a polypill as a 'blanket' approach. If a population strategy offering a polypill to all people over a certain age was to be implemented, it would need to be supported by patient education.


[Acquired von Willebrand's disease type 2A following arteriovenous fistula for haemodialysis?].
Acquired von Willebrand's disease (aVWD) is considered to be an underestimated cause of unexplained bleeding. Adsorption of von Willebrand factor (VWF) to tumour cells or hydroxyethyl starch and elimination of VWF by autoantibodies as well as shear stress-induced mechanical alteration of VWF with concomitant cleavage by enzymes may lead to an acquired deficiency of VWF and a bleeding disorder. We report a 39-year-old woman who developed spontaneous bleeding five years after surgical creation of an arteriovenous fistula (AVF) for haemodialysis treatment. AVWD type 2A was diagnosed after successful renal transplantation. One year after surgical closure of the AVF, the aVWD could not be verified again. Thus, the aVWD may have developed because of altered blood flow and shear stress inside the arteriovenous fistula.


Extracorporeal membrane oxygenation with subclavian artery cannulation in awake patients with pulmonary hypertension.
Pulmonary hypertension (PH) is a challenging disease process to manage. Respiratory and hemodynamic changes that accompany general anesthesia lead to a significant risk of cardiovascular collapse. Certain cases of decompensated PH require extracorporeal membrane oxygenation (ECMO) support as either a bridge to lung transplantation or bridge to recovery. Performing ECMO cannulation without intubation or general anesthesia in these patients may be safer given the severity of their underlying disease process. We present three cases of upper body ECMO cannulation performed on patients with pulmonary hypertension while awake and without mechanical ventilation.


Incidence and burden of long COVID in Africa: a systematic review and meta-analysis.
Long COVID, also known as "post-acute sequelae of COVID-19," affects at least 65 million individuals worldwide with a wide spectrum of symptoms that may last weeks, months, or permanently. Its epidemiology and burden in Africa are unclear. This meta-analysis examines long-term COVID-19 effects in the WHO African Region. A systematic search in several databases was carried out up to 12 February 2023 including observational studies from African countries reporting the cumulative incidence of long COVID signs and symptoms. Only studies conducted in African countries were included. Several sensitivity and meta-regression analyses were performed. Among 1547 papers initially screened, 25 were included, consisting of 29,213 participants. The incidence of any long COVID symptomatology was 48.6% (95% CI 37.4-59.8) as psychiatric conditions were the most frequent, particularly post-traumatic stress disorder reaching a cumulative incidence of 25% (95% CI 21.1-30.4). Higher age (p = 0.027) and hospitalization (p = 0.05) were associated with a higher frequency of long COVID. Long COVID poses a significant burden in Africa, particularly concerning psychiatric conditions. The study recommends identifying at-risk people and defining treatment strategies and recommendations for African long-COVID patients. High-quality studies addressing this condition in African setting are urgently needed.


Synthesis of Novel Pyridine Bearing Biologically Active Imidiazolyl, Pyrazolyl, Oxa/thiadiazolyl and Urea Derivatives as Promising Anticancer Agents.
A novel series of pyridine containing 1,3,4-oxa/thiadiazol derivatives 4a,b, pyrazole derivatives 5-7, thiazole derivatives 9a,b and 17a-c, urea derivatives 12a-c, imidiazole derivative 16, imidazo[1,2-a]pyridine derivatives 18a, b, tetrazole 19, pyrane 20 and pyridine derivatives 21 has been synthesized. This research aims to synthesize 6-(Trifluoromethyl)-2-{[3-(trifluoromethyl)phenyl] amino} nicotinohydrazide 2 and 6-(trifluoromethyl)-2-{[3-(trifluoromethyl)phenyl]amino} pyridin-3-carboaldhyde 15 as key intermediate for the synthesis of novel pyridine derivatives bearing different heterocyclic rings in order to study the additive effect of this ring toward tumor cell lines. 6-(Trifluoromethyl)-2-{[3-(trifluoromethyl)phenyl]amino} nicotinohydrazide 2 was synthesized in a series of synthetic steps and was used as key intermediate for the synthesis of compounds 3-(1,3,4- oxa/thiadiazol-2-yl)-6-(trifluoromethyl)-N-(3- trifluoromethyl) phenyl) pyridin-2-amine 4a,b, (3,5-dimethyl- 1H-pyrazol-1-yl derivatives) [6-(trifluoromethyl)-2-{[3- trifluoromethyl) phenyl] amino} pyridin-3- yl]methanone 5a,b, 6-8, 9a,b and 12a-c. Also, 6-(trifluoromethyl)-2-{[3-(trifluoromethyl)phenyl]amino} pyridin-3-carboaldhyde (15) was used as a key intermediate for the synthesis of novel series of pyridine derivatives with different heterocyclic ring (16-21). Structures of the newly synthesized compounds were established by elemental analysis and spectral data. All the synthesized compounds were screened for their in vitro anticancer activity against liver cancer (HepG2), human colon cancer (HT-29) and human breast adenocarcinoma cell lines (MCF-7). All the synthesized compounds were investigated for their in vitro antitumor activity. Compounds 4b, 9a,b and 19 showed higher antitumor activity than the doxorubicin. Interestingly, pyridine with pfluorophenyl urea 12a demonstrated the most potent antitumor activity. The activity of these compounds is strongly dependent on the basic skeleton of the molecules and the nature of the heterocyclic ring attached to the pyridine moiety.


Single molecule sensing by nanopores and nanopore devices.
Molecular-scale pore structures, called nanopores, can be assembled by protein ion channels through genetic engineering or be artificially fabricated on solid substrates using fashion nanotechnology. When target molecules interact with the functionalized lumen of a nanopore, they characteristically block the ion pathway. The resulting conductance changes allow for identification of single molecules and quantification of target species in the mixture. In this review, we first overview nanopore-based sensory techniques that have been created for the detection of myriad biomedical targets, from metal ions, drug compounds, and cellular second messengers to proteins and DNA. Then we introduce our recent discoveries in nanopore single molecule detection: (1) using the protein nanopore to study folding/unfolding of the G-quadruplex aptamer; (2) creating a portable and durable biochip that is integrated with a single-protein pore sensor (this chip is compared with recently developed protein pore sensors based on stabilized bilayers on glass nanopore membranes and droplet interface bilayer); and (3) creating a glass nanopore-terminated probe for single-molecule DNA detection, chiral enantiomer discrimination, and identification of the bioterrorist agent ricin with an aptamer-encoded nanopore.


Conserved genetic regions across angiosperms as tools to develop single-copy nuclear markers in gymnosperms: an example using cycads.
Several individuals of the Caribbean Zamia clade and other cycad genera were used to identify single-copy nuclear genes for phylogeographic and phylogenetic studies in Cycadales. Two strategies were employed to select target loci: (i) a tblastX search of Arabidopsis conserved ortholog sequence (COS) set and (ii) a tblastX search of Arabidopsis-Populus-Vitis-Oryza Shared Single-Copy genes (APVO SSC) against the EST Zamia databases in GenBank. From the first strategy, 30 loci were selected, and from the second, 16 loci. In both cases, the matching GenBank accessions of Zamia were used as a query for retrieving highly similar sequences from Cycas, Picea, Pinus species or Ginkgo biloba. After retrieving and aligning all the sequences in each locus, intron predictions were completed to assist in primer design. PCR was carried out in three rounds to detect paralogous loci. A total of 29 loci were successfully amplified as a single band of which 20 were likely single-copy loci. These loci showed different diversity and divergence levels. A preliminary screening allowed us to select 8 promising loci (40S, ATG2, BG, GroES, GTP, LiSH, PEX4 and TR) for the Zamia pumila complex and 4 loci (COS26, GroES, GTP and HTS) for all other cycad genera.


The nutrition of the budgerigar (Melopsittacus undulatus).
Growing interest in the nutrition of the budgerigar (Melopsittacus undulatus) has highlighted the paucity of knowledge in this area. The aims of this study were to review the available literature on their individual nutrient requirements and relate this to the nutrient content of their predominantly seed-based diet and to investigate the effect of the bird's daily energy requirement on the fluctuations in body weight. Studies were conducted at the Waltham Centre to measure the relationship between daily metabolizable energy intake (kJ/kg BW) and body weight change (g/d) for groups of adult budgerigars. The birds were found to require daily 48-128 kJ/bird depending on their body mass (birds in our colony typically weigh 30-80 g). During a series of breeding trials the daily energy intake for a breeding pair plus their three chicks, at peak energy intake, was found to be 483-505 kJ (at pairing, the mean daily energy intake of the breeding pairs was 231 kJ). Apparent metabolizability of the major nutrients from a seed diet were generally found to be greater than 80%, which allows these birds to assimilate the high levels of energy needed for their basal metabolism. In summary, the nutrient requirements of the budgerigar (where known) were found to be similar to those of other avian species, however, further work is needed, especially in the area of availability of key nutrients. Further developments in the dietary management of these birds will only be possible if researchers can overcome the birds' poor acceptance of novel foods and satisfy their high basal energy requirements before establishing their requirements for individual nutrients.


Vascular risk factor profiles in the first phase of the Scottish Heart and Arterial Risk Prevention (SHARP) Survey, 1991-1996.
The SHARP survey data comprises personal information, family history, lifestyle and risk factor prevalence for 19,400 men and women sampled from the Scottish working population between 1991 and 1996. The purpose of the survey was the achievement of a clearer understanding of coronary risk factor prevalence in the working population of Scotland; the education of that population through counselling and advice; and a clearer appreciation of an individual's risk factor profile as a predictor for future events. In this paper a selection of attributes is explored for the information they yield about the characteristics of an apparently healthy population. Comparisons are drawn with earlier studies. A mobile risk factor screening unit toured workplaces throughout Scotland and recorded information on age, sex, occupation, social class, personal and family history, smoking, alcohol and salt consumption, body mass index, blood pressure, glucose and total cholesterol. The variation in measured levels for common risk factors in a sample of apparently healthy Scottish people shows substantial differences from the measured variation in an unstratified survey. Across all conventional coronary risk factor measurements, working Scottish people are uniformly "more healthy" than the general population. A comparison of trend with age for male and female smokers and non-smokers in cholesterol level shows no difference between smokers and non-smokers; a similar comparison for body mass index and weight shows some consistent differences but without statistical significance.


[Effect of low intensity helium-neon laser and decimeter electromagnetic irradiation on functional indices of immune cells in patients with rheumatoid arthritis].
Clinical, laboratory, and immunoassay of 58 patients with rheumatoid arthritis, first and second degree of activity was carried out. Low-energy helium-neon laser exposure and decimeter electromagnetic radiation (DMEM) of peripheral blood was given along with the use of non-steroidal antiinflammatory drugs and methotrexate. Peculiarities of this magnetic-laser effect on proliferation response and apoptosis of mononuclear leucocytes in vitro and in vivo have been revealed. It was also established that the application of DMEM-therapy brought patients with RA in shorter period of time to clinical improvement evaluated by ACR criteria.


Diffusion-weighted MRI versus 18F-FDG PET/CT: performance as predictors of tumor treatment response and patient survival in patients with non-small cell lung cancer receiving chemoradiotherapy.
The purpose of this study was to compare the predictive capabilities of diffusion-weighted MRI (DWI) and 18F-FDG PET/CT for tumor response to therapy and survival in patients with non-small cell lung cancer (NSCLC) receiving chemoradiotherapy. The study included 64 patients with NSCLC diagnosed as stage III who underwent pretherapeutic DWI and FDG PET/CT and were treated with chemoradiotherapy. For quantitative prediction, apparent diffusion coefficient (ADC) for DWI and maximum standardized uptake value (SUVmax) for PET/CT were measured at all targeted lesions and averaged to obtain final values for each patient. To evaluate the predictive capability of either index for distinguishing partial response and nonresponse (stable or progressive disease) groups, receiver operating characteristic analysis was performed, and sensitivity, specificity, and accuracy of the two modalities were compared using the McNemar test. Finally, overall and progression-free survival curves divided by the corresponding threshold value were compared by means of the log-rank test. The area under the curve (Az) for ADC (Az=0.84) was significantly larger than that for SUVmax (Az=0.64, p<0.05). The application of feasible threshold values resulted in specificity (44.4%) and accuracy (76.6%) of DWI becoming significantly higher than those of PET/CT (specificity, 11.1%; p<0.05 and accuracy, 67.2%, p<0.05). In addition, only overall survival and progression-free survival of the two groups divided by ADC at 2.1×10(-3) mm2/s and SUVmax at 10 showed a significant difference (p<0.05). DWI may have better potential than FDG PET/CT for prediction of tumor response to therapy in NSCLC patients before chemoradiotherapy.


Methods for Handling Missing Data in the Behavioral Neurosciences: Don't Throw the Baby Rat out with the Bath Water.
Missing data are a major problem in the behavioral neurosciences, particularly when data collection is costly. Often researchers exclude cases with missing data, which can result in biased estimates and reduced power. Trying to avoid the deletion of a case because of a missing data point can be conducted, but implementing a naïve missing data method can result in distorted estimates and incorrect conclusions. New approaches for handling missing data have been developed but these techniques are not typically included in undergraduate research methods texts. The topic of missing data techniques would be useful for teaching research methods and for helping students with their research projects. This paper aimed to illustrate that estimating missing data is often more efficacious than complete case analysis, otherwise known as listwise deletion. Longitudinal data was obtained from an experiment examining the effects of an anorectic drug on food consumption in a small sample (n=17) of rats. The complete dataset was degraded by removing a percentage of datapoints (1-5%, 10%). Four missing data techniques: listwise deletion, mean substitution, regression, and expectation-maximization (EM) were applied to all six datasets to ensure that each approach was applied to the same missing data points. P-values, effect sizes, and Bayes factors were computed. Results demonstrated listwise deletion was the least effective method. EM and regression imputation were the preferred methods when more than 5% of the data were missing. Based on these findings it is recommended that researchers avoid using listwise deletion and consider alternative missing data techniques.


Specific inhibitors of the three RNA polymerases from the aquatic fungus Blastocladiella emersonii.
Specific inhibitors of each of the three RNA polymerases of Blastocladiella emersonii have been found. Cycloheximide specifically inhibited the in vitro activity of the DEAE-fraction I enzyme, alpha-amanitin specifically inhibited the DEAE-fraction II enzyme, and rifampicin specifically inhibited the fraction III enzyme. DNA stimulation and dependency on the four riboside triphosphates were shown to be characteristic of each of the three fractions. Optimum concentrations of magnesium ions required were shown to differ among the three fractions and to be somewhat higher than optimum concentrations of manganese ions. The effect of pH on activity was essentially identical for each of the three fractions. Kinetic experiments and nuclease assays indicated the presence of some interfering substances in the partially purified RNA polymerase fractions.


Mechanical interactions between four heart chambers with and without the pericardium in canine hearts.
By using excised postmortem hearts obtained from 15 mongrel dogs with the pericardium intact, we investigated mechanical interactions between the four heart chambers from the standpoint of ventricular pressure-volume relationships. The interactions investigated were those between (1) the atrium and the ventricle, (2) the right ventricle and left ventricles, (3) the atrium and one ventricle vs. the other ventricle, and finally (4) the left and right atrium and the right ventricle vs. the left ventricle. For these purposes, we inserted compliant balloons into the four heart chambers without injuring the pericardium, i.e., we incised the base of the atria which was not covered with the pericardium. We obtained the right and/or left ventricular pressure-volume relationships under a constant pressure in three other heart chambers by changing the height of the reservoir connected to each balloon. As a result, both ventricular pressure-volume relationships were hardly affected by an increase in the atrial pressure ranging from 5 to 30 cm H2O with the pericardium removed, although the ventricle became less compliant due to an increase of the same magnitude of the opposite ventricular pressure. On the other hand, the effect of an increase in atrial pressure was distinct with the pericardium intact. Also, all mechanical interactions were enhanced dramatically with the intact pericardium. Thus, the pericardium plays an important role in these mechanical interactions, especially when the filling pressures of all heart chambers increase simultaneously. Clinically, these findings may be important to understanding ventricular functions as related to various heart disease-especially acute heart failure.


A Bioinspired Dynamics-Based Adaptive Fuzzy SMC Method for Half-Car Active Suspension Systems With Input Dead Zones and Saturations.
Active suspension systems are widely used in vehicles to improve ride comfort and handling performance. However, existing control strategies may be limited by various factors, including insufficient consideration of different operation conditions, such as changing in vehicle mass, defects in strategy design leading to incapability for guaranteeing finite-time stability, lack of considering input effects of dead zone and saturation, excessive energy cost, etc. Importantly, very few results considered the energy-saving performance of active suspension systems although a well-perceived issue in practice. An adaptive fuzzy SMC method based on a bioinspired reference model is established in this article, which is to purposely address these problems and be able to provide finite-time convergence and energy-saving performance simultaneously. The proposed control method effectively utilizes beneficial nonlinear stiffness and nonlinear damping properties that the bioinspired reference model could provide. Therefore, superior vibration suppression performance with less energy consumption and improved ride comfort can all be obtained readily. By using a fuzzy-logic system (FLS), the proposed method is beneficial in compensating for system parameter uncertainties, external disturbances, input dead zones, and saturations. Furthermore, based on the adaptive PD-SMC method, the tracking errors can converge to zeros in finite time. The stability of the equilibrium point of all the states in active suspension systems is theoretically proven by Lyapunov techniques. Finally, simulation results are provided to verify the correctness and effectiveness of the proposed control scheme.


Single-pixel imaging 12 years on: a review.
Modern cameras typically use an array of millions of detector pixels to capture images. By contrast, single-pixel cameras use a sequence of mask patterns to filter the scene along with the corresponding measurements of the transmitted intensity which is recorded using a single-pixel detector. This review considers the development of single-pixel cameras from the seminal work of Duarte et al. up to the present state of the art. We cover the variety of hardware configurations, design of mask patterns and the associated reconstruction algorithms, many of which relate to the field of compressed sensing and, more recently, machine learning. Overall, single-pixel cameras lend themselves to imaging at non-visible wavelengths and with precise timing or depth resolution. We discuss the suitability of single-pixel cameras for different application areas, including infrared imaging and 3D situation awareness for autonomous vehicles.


[Epidemiology of cardiovascular diseases in the Spanish elderly population].
This paper is a comprehensive and critical review of the updated information available in Spain for the elderly population on the epidemiology of cardiovascular diseases. Clinical (coronary heart disease, heart failure, and cerebrovascular disease) and subclinical (left ventricular hypertrophy, carotid stenosis) cardiovascular diseases are reviewed. Prevalence and distribution of major classical cardiovascular risk factors such as hypertension, hyperlipidemia, diabetes mellitus and smoking and information on new risk factors such as microalbuminuria or abdominal obesity are also presented. The article is also focused on the high rates of morbidity, mortality and the burden of handicap in this age group in comparison with middle-aged people. Finally we call attention to the few and inconsistent population data available for some of the mentioned topics in our country, particularly the lack of specific figures of incidence and risk rates from cohort studies of elderly people in Spain.


Structural insight into the human immunodeficiency virus Vif SOCS box and its role in human E3 ubiquitin ligase assembly.
Human immunodeficiency virus (HIV) virion infectivity factor (Vif) causes the proteasome-mediated destruction of human antiviral protein APOBEC3G by tethering it to a cellular E3 ubiquitin ligase composed of ElonginB, ElonginC, Cullin5, and Rbx2. It has been proposed that HIV Vif hijacks the E3 ligase through two regions within its C-terminal domain: a BC box region that interacts with ElonginC and a novel zinc finger motif that interacts with Cullin5. We have determined the crystal structure of the HIV Vif BC box in complex with human ElonginB and ElonginC. This complex presents direct structural evidence of the recruitment of a human ubiquitin ligase by a viral BC box protein that mimics the conserved interactions of cellular ubiquitin ligases. We further mutated conserved hydrophobic residues in a region downstream of the Vif BC box. These mutations demonstrate that this region, the Vif Cullin box, composes a third E3-ligase recruiting site critical for interaction between Vif and Cullin5. Furthermore, our homology modeling reveals that the Vif Cullin box and zinc finger motif may be positioned adjacent to the N terminus of Cullin5 for interaction with loop regions in the first cullin repeat of Cullin5.


Comparison of oncological outcomes of right-sided colon cancer versus left-sided colon cancer after curative resection: Which side is better outcome?
There are embryological origins, anatomical, histological, genetic, and immunological differences between right-sided colon cancer (RCC) and left-sided colon cancer (LCC). Many studies have sought to determine the survival and prognosis according to tumor location. This study aimed to analyze outcomes between RCC and LCC. Between January 2000 and December 2012, data on 414 patients who underwent curative resection for RCC and LCC were retrieved from a retrospective database. Propensity score matching (1:1) was performed and RCC was identified in 207 and LCC in 207 patients. On average, RCC exhibited a more advanced N stage, increased tumor size, more frequently poorly differentiated tumors, more harvested lymph nodes, and more positivity of lymphovascular invasion than LCC. With a median follow-up of 66.7 months, the 5-year overall survival (OS) rates for RCC and LCC were 82.1% and 88.7%, respectively, (P < .05). The 5-year disease-free survival (DFS) rates were 81.4% (RCC) and 88.3% (LCC; P < .05). In stage III cancers, the DFS rates were 61.1% (RCC) and 81.9% (LCC; P < .05), while the OS rates were 65.6% (RCC) and 78.6% (LCC; P = .056). On the basis of present data, LCC exhibited better survival outcomes than RCC after curative resection. Especially in stage III, LCC showed better oncologic outcomes. Proper specialized treatment related to the location of colon cancer is needed.


Drosophila S6 Kinase like inhibits neuromuscular junction growth by downregulating the BMP receptor thickveins.
Synaptic connections must be precisely controlled to ensure proper neural circuit formation. In Drosophila melanogaster, bone morphogenetic protein (BMP) promotes growth of the neuromuscular junction (NMJ) by binding and activating the BMP ligand receptors wishful thinking (Wit) and thickveins (Tkv) expressed in motor neurons. We report here that an evolutionally conserved, previously uncharacterized member of the S6 kinase (S6K) family S6K like (S6KL) acts as a negative regulator of BMP signaling. S6KL null mutants were viable and fertile but exhibited more satellite boutons, fewer and larger synaptic vesicles, larger spontaneous miniature excitatory junctional potential (mEJP) amplitudes, and reduced synaptic endocytosis at the NMJ terminals. Reducing the gene dose by half of tkv in S6KL mutant background reversed the NMJ overgrowth phenotype. The NMJ phenotypes of S6KL mutants were accompanied by an elevated level of Tkv protein and phosphorylated Mad, an effector of the BMP signaling pathway, in the nervous system. In addition, Tkv physically interacted with S6KL in cultured S2 cells. Furthermore, knockdown of S6KL enhanced Tkv expression, while S6KL overexpression downregulated Tkv in cultured S2 cells. This latter effect was blocked by the proteasome inhibitor MG132. Our results together demonstrate for the first time that S6KL regulates synaptic development and function by facilitating proteasomal degradation of the BMP receptor Tkv.


Human islet amyloid polypeptide at the air-aqueous interface: a Langmuir monolayer approach.
Human islet amyloid polypeptide (hIAPP) is the source of the major component of the amyloid deposits found in the islets of Langerhans of around 95 per cent type 2 diabetic patients. The formation of aggregates and mature fibrils is thought to be responsible for the dysfunction and death of the insulin-producing pancreatic β-cells. Investigation on the conformation, orientation and self-assembly of the hIAPP at time zero could be beneficial for our understanding of its stability and aggregation process. To obtain these insights, the hIAPP at time zero was studied at the air-aqueous interface using the Langmuir monolayer technique. The properties of the hIAPP Langmuir monolayer at the air-aqueous interface on a NaCl subphase with pH 2.0, 5.6 and 9.0 were examined by surface pressure- and potential-area isotherms, UV-Vis absorption, fluorescence spectroscopy and Brewster angle microscopy. The conformational and orientational changes of the hIAPP Langmuir monolayer under different surface pressures were characterized by p-polarized infrared-reflection absorption spectroscopy, and the results did not show any prominent changes of conformation or orientation. The predominant secondary structure of the hIAPP at the air-aqueous interface was α-helix conformation, with a parallel orientation to the interface during compression. These results showed that the hIAPP Langmuir monolayer at the air-aqueous interface was stable, and no aggregate or domain of the hIAPP at the air-aqueous interface was observed during the time of experiments.


[Radioisotope decontamination of X-ray detector (photostimulable phosphor plate)].
We tried to remove contamination of radioisotope (RI) for an X-ray detector (photostimulable phosphor plate; IP) and verified that our procedure suggested by Nishihara et al. was effective for decontamination. The procedure was as follows. First, the IP was kept for approximately twelve hours, and then it was processed [image (A)] as well as a clinical processing mode. Second, using a wet-type chemical wiper, we scavenged the IP to remove the adhered RI on its surface. Then, once again, the IP was kept for approximately fifteen hours and processed [image (B)] in order to check an effect of decontamination. Finally, the two images of (A) and (B) were analyzed using ImageJ, which can be downloaded as a free software, and a percentage of removal was calculated. The procedure was applied to two IPs using the FCR 5501 plus. In the present case, the percentage of removal was approximately 96%. The removed radioisotopes in the chemical wipers were analyzed by Ge detector. Then, (134)Cs and (137)Cs were found with activities of 2.9 4.3 Bq and 3.5 5.2 Bq, respectively. For three months after that, we cannot see black spots on the IPs owing to the contamination of the RI and there are no defects caused by decontamination using a wet-type chemical wiper.


The Effects of Resection Technique on Implant Migration in Single Radius Posterior-Stabilized Total Knee Replacement.
The purpose of the present study was to measure the effects of gap balancing and resection techniques on migration of a single total knee replacement implant design. A total of 23 patients (24 knees) were recruited on referral to either a surgeon performing gap balancing or a surgeon performing measured resection and followed prospectively. All patients received a fixed bearing, posterior stabilized total knee replacement implant of a single radius femoral component design with cement fixation, and all aspects of care outside of resection technique were identical. Patients underwent radiostereometric analysis (RSA) at 2 weeks (baseline), 6 weeks, 3 months, 6 months, 1 year, and 2 years. Migration of the tibial and femoral components was compared between groups. Tibial component migration was greater at 2 years in the gap balancing group (mean difference = 0.336 mm, p = 0.036), but there was no difference at 1 year. One measured resection and three gap balancing tibial components demonstrated continuous migration > 0.2 mm between years 1 and 2. There was no difference in femoral component migration. Small differences in tibial component migration were found between the gap balancing and measured resection techniques. However, comparing the migration to established predictive thresholds for long-term loosening risk, implants performed with both techniques were found to have equally low revision risk.


Periodic migrainous neuralgia: a cause of dental pain.
The clinical findings in thirty-five cases of periodic migrainous neuralgia (PMN) are given. Typical case histories are used to illustrate the fact that the condition may mimic dental pain. The nomenclature and association of the condition with migraine are briefly discussed, and a plea is made that the condition always be considered in cases of facial pain, when other clinical features of the disease are present, in order to save needless loss of teeth and delay in treatment.


Mesenteric fibromatosis.
Two rare cases of mesenteric fibromatosis are presented. The first patient had a right upper quadrant mass and colicky abdominal pain. The tumor originated from the mesentery of the colon and it infiltrated the gallbladder, cystic duct, and the liver. The second patient had severe hematemesis and melena. The origin of the tumor, which infiltrated 3/4 part of the stomach, the gastrohepatic ligament, the first part of the duodenum, and the liver could not be determined. In the first patient, partial colectomy and cholecystectomy were performed and the liver lesion was completely excised. The second patient underwent subtotal gastrectomy and left lobectomy of the liver. The first part of the duodenum was excised. Gastrojejunostomy was performed. No recurrence was recorded in either patients during 16 and 13 months follow-up, respectively. In this report, diagnostic aids, differential diagnosis and treatment of this rare disease are discussed.


Acculturation's influence on antifat attitudes, body image and eating behaviors.
Antifat attitudes (AFA) refer to the belief that overweight and obese individuals are responsible for their weight. Using 264 Latina and European American females, a regression showed that AFA positively correlated with body dissatisfaction and eating concerns. An ANOVA revealed that European American females reported significantly greater AFA than Latinas. Furthermore, European American females and high acculturated Latinas reported significantly greater AFA than both bicultural and low acculturated Latinas. No differences existed between European Americans and high acculturated Latinas. Language-use significantly interacted with body dissatisfaction to predict AFA. The role of AFA, acculturation, and suggestions for future research are discussed.


Biochemical and functional analysis of COS3A, a novel CD63-specific monoclonal antibody.
Monoclonal antibodies (mAbs) have become essential tools in life science research and in medicine, because of their extreme specificity. Several mAbs against leukocyte surface molecules have been generated in our laboratory. From these, mAb COS3A was selected for biochemical and functional analysis. To analyze the properties and function of the mAb COS3A. Cellular distribution was analyzed by immunofluorescence staining and flow cytometry. Biochemical characterization of the molecular target of COS3A was approached by immunoprecipitation, Western blotting and amino acid sequencing using LC-MS. N-glycosidase F treatment of COS3A-precipitated protein and culture of U937 cells in the presence of tunicamycin before cell lysate preparation were used to study the glycosylation state of proteins. Phagocytosis was examined by flow cytometry. MAb COS3A bound specifically to a molecule expressed on the surface of various human hematopoietic cells and cell lines but not on erythrocytes. The antigen had a molecular weight of 30-70 kDa, which was reduced to 25 kDa by elimination of N-linked glycan. LC-MS data and immunoprecipitation indicated that mAb COS3A bound specifically to the CD63 molecule. Remarkably, functional analysis demonstrated that mAb COS3A dramatically reduced granulocyte phagocytosis. The mAb COS3A recognized the CD63 molecule and strongly diminished granulocyte phagocytosis of E. coli, suggesting that CD63 may play a crucial role in the initial step of phagocytosis. MAb COS3A is, therefore, suitable for both biochemical and functional studies of CD63, and may be used for further study of the mechanism of phagocytosis and also in therapeutic approaches.


Is it Williams syndrome? GTF2IRD1 implicated in visual-spatial construction and GTF2I in sociability revealed by high resolution arrays.
Genetic contributions to human cognition and behavior are clear but difficult to define. Williams syndrome (WS) provides a unique model for relating single genes to visual-spatial cognition and social behavior. We defined a approximately 1.5 Mb region of approximately 25 genes deleted in >98% of typical WS and then rare small deletions, showing that visual-spatial construction (VSC) in WS was associated with the genes GTF2IRD1 and GTF2I. To distinguish the roles of GTF2IRD1 and GTF2I in VSC and social behavior, we utilized multiple genomic methods (custom high resolution oligonucleotide microarray, multicolor FISH and somatic cell hybrids analyzed by PCR) to identify individuals deleted for either gene but not both. We analyzed genetic, cognitive and social behavior in a unique individual with WS features (heart defects, small size, facies), but with an atypical deletion of a set of genes that includes GTF2IRD1, but not GTF2I. The centromeric breakpoint localized to the region 72.32-72.38 Mb and the telomeric breakpoint to 72.66 Mb, 10 kb downstream of GTF2IRD1. Cognitive testing (WPPSI-R, K-BIT, and PLS-3) demonstrated striking deficits in VSC (Block Design, Object Assembly) but overall performance 1.5-3 SD above WS means. We have now integrated the genetic, clinical and cognitive data with previous reports of social behavior in this subject. These results combine with previous data from small deletions to suggest the gene GTF2IRD1 is associated with WS facies and VSC, and that GTF2I may contribute to WS social behaviors including increased gaze and attention to strangers.


Application of genotyping-by-sequencing on semiconductor sequencing platforms: a comparison of genetic and reference-based marker ordering in barley.
The rapid development of next-generation sequencing platforms has enabled the use of sequencing for routine genotyping across a range of genetics studies and breeding applications. Genotyping-by-sequencing (GBS), a low-cost, reduced representation sequencing method, is becoming a common approach for whole-genome marker profiling in many species. With quickly developing sequencing technologies, adapting current GBS methodologies to new platforms will leverage these advancements for future studies. To test new semiconductor sequencing platforms for GBS, we genotyped a barley recombinant inbred line (RIL) population. Based on a previous GBS approach, we designed bar code and adapter sets for the Ion Torrent platforms. Four sets of 24-plex libraries were constructed consisting of 94 RILs and the two parents and sequenced on two Ion platforms. In parallel, a 96-plex library of the same RILs was sequenced on the Illumina HiSeq 2000. We applied two different computational pipelines to analyze sequencing data; the reference-independent TASSEL pipeline and a reference-based pipeline using SAMtools. Sequence contigs positioned on the integrated physical and genetic map were used for read mapping and variant calling. We found high agreement in genotype calls between the different platforms and high concordance between genetic and reference-based marker order. There was, however, paucity in the number of SNP that were jointly discovered by the different pipelines indicating a strong effect of alignment and filtering parameters on SNP discovery. We show the utility of the current barley genome assembly as a framework for developing very low-cost genetic maps, facilitating high resolution genetic mapping and negating the need for developing de novo genetic maps for future studies in barley. Through demonstration of GBS on semiconductor sequencing platforms, we conclude that the GBS approach is amenable to a range of platforms and can easily be modified as new sequencing technologies, analysis tools and genomic resources develop.


Gas embolism during laparoscopic liver resection in a pig model: frequency and severity.
Laparoscopic liver surgery is evolving rapidly. Carbon dioxide embolism is a potential complication. The aim of this work was to study the frequency and severity of gas embolism (GE) during laparoscopic liver lobe resection in a pig model and the resulting cardiovascular and respiratory changes. Fifteen anaesthetized piglets underwent laparoscopic left liver lobe resection. Haemodynamic and respiratory variables were monitored, including systemic and pulmonary arterial pressures, end-tidal CO2, and pulmonary dead space. Online blood gas monitoring and a transoesophageal echocardiography (TOE) were used. GE was graded semi-quantitatively as grade 0 (none), grade 1 (minor), or grade 2 (major), depending on the TOE results. In 10 of 15 piglets, GE occurred. In total, 33 separate episodes of GE were recorded. All 13 episodes of grade 2 and three of grade 1 were serious enough to cause mainly respiratory, but also haemodynamic effects. Mostly, grade 1 GE caused only minor respiratory or haemodynamic changes. Most variables were affected during grade 2 GE; the most important were Pa(o(2)), Pa(co(2)), end-tidal CO2, Vd/Vt, and mean pulmonary arterial pressure. GE occurred frequently during laparoscopic liver resection in this experimental study. Approximately half of the embolisms were serious enough to cause respiratory or haemodynamic disturbances or both. Pending further human studies, a combination of several monitoring techniques, with narrow limits for the alarm settings, will ensure correct interpretation of the complex physiological response to GE and reveal it early enough to alert the anaesthetist and the surgeon to the ongoing problem.


Transformation in heterokaryons of Neurospora crassa is nuclear rather than cellular phenomenon.
In Neurospora crassa, multinucleate macroconidia are used for genetic transformation. The barrier for such a transformation can be either at the cell membrane level or at the nuclear membrane level. For assessment of these possibilities, a forced heterokaryon (containing two genetically marked nuclei and auxotrophic for histidine) of Neurospora crassa was transformed with a plasmid containing his-3+ gene. The transformants, which could grow without histidine supplementation, were then resolved into component homokaryons to determine into which nucleus or nuclei the plasmid had entered. Our results suggest that the barrier for transformation in Neurospora crassa is at the nuclear level, not at the cell membrane level. In a heterokaryon containing two genetically distinct nuclei, plasmid DNA integrated into only one of the nuclear types at any instance, but never into both nuclear types. Thus, in Neurospora crassa, the competent nucleus is essential for the transformation event to take place, and at a given time only one type of nucleus is competent to take up the exogenous DNA. Genomic Southern analysis showed that the transformants harbor both ectopic and homologous integrations of the plasmid DNA. The type and number of integrations were reflected at the post-translational level, since the specific activity of histidinol dehydrogenase (the translation product of his-3+ gene) was variable among several transformants and always less than the level of the wild type.


Dose-escalation study of the pharmacokinetics and pharmacodynamics of rivaroxaban in healthy elderly subjects.
The aim of this study was to investigate the pharmacokinetics and pharmacodynamics of rivaroxaban--a novel, oral, direct Factor Xa (FXa) inhibitor--in healthy elderly subjects. In this single-centre, single-blind, placebo-controlled, parallel-group, dose-escalation study, 48 subjects (aged 60-76 years) were randomized to receive a single oral dose of 30, 40 or 50 mg of rivaroxaban or placebo. Rivaroxaban was absorbed rapidly, reaching peak plasma concentration (C(max)) 4 h after dosing in all groups. Bioavailability, in terms of the area under the plasma concentration-time curve (AUC) and C(max), increased slightly (less than dose proportionally) after administration of rivaroxaban 40 mg compared with 30 mg, but was not increased further with rivaroxaban 50 mg. Rivaroxaban pharmacodynamic effects (inhibition of FXa activity and prolongation of prothrombin time, activated partial thromboplastin time and HepTest) all showed a similar pattern, with maximum inhibition of FXa activity increasing from 68% after rivaroxaban 30 mg to 75% after 40 mg and no further increase with the 50 mg dose. Most adverse events were mild; observed rates were less than placebo for the 30 and 40 mg dose groups, and similar to placebo for 50 mg. No differences were found between male and female subjects. Effects of rivaroxaban doses above 50 mg were not investigated in this study. Each single dose of rivaroxaban was well tolerated, with predictable pharmacokinetics and pharmacodynamics at doses up to 40 mg, and provided effective anticoagulation in healthy elderly subjects. Adverse events were somewhat elevated in the 50 mg group, but given the small sample size, no specific conclusions can be drawn about this dosing level.


In situ reactivation of glycerol-inactivated coenzyme B12-dependent enzymes, glycerol dehydratase and diol dehydratase.
The catalytic properties of coenzyme B12-dependent glycerol dehydratase and diol dehydratase were studied in situ with Klebsiella pneumoniae cells permeabilized by toluene treatment, since the in situ enzymes approximate the in vivo conditions of the enzymes more closely than enzymes in cell-free extracts or cell homogenates. Both dehydratases in situ underwent rapid "suicidal" inactivation by glycerol during catalysis, as they do in vitro. The inactivated dehydratases in situ, however, were rapidly and continually reactivated by adenosine 5'-triphosphate (ATP) and Mn2+ in the presence of free adenosylcobalamin, although in cell-free extracts or in cell homogenates they could not be reactivated at all under the same reaction conditions. ATP was partially replaced by cytidine 5'-triphosphate or guanosine 5'-triphosphate but not by the beta, gamma-methylene analog of ATP in the in situ reactivation. Mn2+ was fully replaced by Mg2+ but only partially by Co2+. Hydroxocoblamin could not replace adenosylcobalamin in reactivation mixtures. The ability to reactivate the glycerol-inactivated dehydratases in situ was only seen in cells grown anaerobically in glycerol-containing media. This suggests that some factor(s) required for in situ reactivation is subject to induction by glycerol. Of the two possible mechanisms of in situ reactivation, i.e., the regeneration of adenosylcobalamin by Co-adenosylation of the bound inactivated coenzyme moiety (B12-adenosylation mechanism) and the displacement of the bound inactivated coenzyme moiety by free adenosyl-cobalamin (B12-exchange mechanism), the former seems very unlikely from the experimental results.


[Inhibitory effects of "Goishi-tea" as a post-fermented-tea on dietary-induced hypercholesteremia and atherosclerosis in rabbits].
Since lipid oxidation is involved in the deterioration of hypercholesterolemia-related atherosclerosis, ingestion of drinks and foods with antioxidant actions is useful for preventing lipid oxidation. Goishi-tea is a post-fermented-tea manufactured by a unique method in Japan, and may be useful for preventing various disorders. However, there is no scientific evidence. In this study, we compared the radical scavenging activity of goishi-tea with that of other teas, and administered this tea to a rabbit model of hypercholesteremia to evaluate its usefulness in the inhibition of hypercholesteremia and atherosclerosis. The radical scavenging activity of goishi-tea was similar to that of green-tea, and was higher than that of other types of fermented-teas. On the other hand, some difference of components was found between goishi-tea and green-tea. In cholesterol-fed rabbits, low-density lipoprotein (LDL)-cholesterol level in the goishi-tea-group was lower than that in the green-tea-group. Plasma lipidperoxide value was also lower in the goishi-tea-group than in the green-tea and tap-water-groups. On aortic endothelial staining, fat area in the goishi-tea-group was lower than that in the tap-water-group. Furthermore, fat accumulation in the aortic intima in the goishi-tea-group was very low. Goishi-tea has higher antioxidant activities than the other fermented-teas tested, which were generally low, and decreased serum lipid levels, suggesting that goishitea is a very peculiar fermented-tea with usefulness in the prevention of hypercholesterolemia and atherosclerosis.


Caffeine and catechin towards prevention of drug induced oxidation of hemoglobin: A spectroscopic study.
Administration of low doses of nitrates over prolonged periods in patients suffering from coronary heart disease may lead to chronic methemoglobinemia, a disease caused by oxidation of hemoglobin. Previous reports have shown that natural products like curcumin, vitamin E, vitamin C, resveratrol, etc., are capable of inhibition of nitrite induced oxidation of hemoglobin. Hence in this study we aimed to investigate the preventive role of antioxidants present in our diet, like caffeine and catechin hydrate which are commonly found in coffee and tea towards methemoglobin (met-Hb) formation. Our study revealed that when the hemolysate was pre-incubated with equimolar concentration of caffeine and its metabolite with respect to nitrite, the rate of the nitrite induced oxidation of HbA decreased from (7.33 ± 0.54) × 10-5 min-1 to (7.09 ± 1.05) × 10-5 min-1 and (2.98 ± 0.06) × 10-5 min-1 respectively. Hence it was evident that the metabolite of caffeine, 1-methyluric acid, exhibited better efficiency at physiological concentration than its precursor. On the contrary, only 4 mM catechin hydrate could enhance the rate of methemoglobin formation even in absence of nitrite and the rate of the reaction was (6.088 ± 0.31) × 10-5 min-1 which is comparable with that of 400 μM nitrite.


Transformation of plastids in the leaves of Acer negundo L. var. odessanum (H. Rothe).
The leaves of Acer negundo L. var. odessanum (H. Rothe), if permanently exposed to strong sunlight, do not green, but remain yellow and finally become bleached. In yellow leaves the plastids contain single thylakoids and no grana. In plastids of bleached leaves, however, only vesicles are present. The concentration of chlorophylls and photosynthetic activity are much lower in those leaves than in the green ones. If the illumination is reduced (e.g. by shading) both the yellow and the bleached leaves become greenish, and even fully green after a few days at a sufficiently low light intensity. The plastids of yellow-green leaves contain small grana. In dark green leaves the thylakoid system of the chloroplasts is normally developed forming true grana, regardless of whether the leaves were originally green, or became green by shading the yellow or bleached ones. Their pigment concentration and photosynthetic activity are also normal. If green leaves are exposed to sunlight they do not yellow or bleach. During a 3-week period the structure of the thylakoid system did not perceivably change, with the exception that large plastoglobules formed in the stroma.


Monitoring disease activity and progression in Crohn's disease. A Swiss perspective on the IBD ahead 'optimised monitoring' recommendations.
The structured IBD Ahead 'Optimised Monitoring' programme was designed to obtain the opinion, insight and advice of gastroenterologists on optimising the monitoring of Crohn's disease activity in four settings: (1) assessment at diagnosis, (2) monitoring in symptomatic patients, (3) monitoring in asymptomatic patients, and (4) the postoperative follow-up. For each of these settings, four monitoring methods were discussed: (a) symptom assessment, (b) endoscopy, (c) laboratory markers, and (d) imaging. Based on literature search and expert opinion compiled during an international consensus meeting, recommendations were given to answer the question 'which diagnostic method, when, and how often'. The International IBD Ahead Expert Panel advised to tailor this guidance to the healthcare system and the special prerequisites of each country. The IBD Ahead Swiss National Steering Committee proposes best-practice recommendations adapted for Switzerland. The IBD Ahead Steering Committee identified key questions and provided the Swiss Expert Panel with a structured literature research. The expert panel agreed on a set of statements. During an international expert meeting the consolidated outcome of the national meetings was merged into final statements agreed by the participating International and National Steering Committee members - the IBD Ahead 'Optimized Monitoring' Consensus. A systematic assessment of symptoms, endoscopy findings, and laboratory markers with special emphasis on faecal calprotectin is deemed necessary even in symptom-free patients. The choice of recommended imaging methods is adapted to the specific situation in Switzerland and highlights the importance of ultrasonography and magnetic resonance imaging besides endoscopy. The recommendations stress the importance of monitoring disease activity on a regular basis and by objective parameters, such as faecal calprotectin and endoscopy with detailed documentation of findings. Physicians should not rely on symptoms only and adapt the monitoring schedule and choice of options to individual situations.


Alanine aminotransferase catalyses the breakdown of alanine after hypoxia in Arabidopsis thaliana.
Alanine aminotransferase (AlaAT) catalyses the reversible transfer of an amino group from glutamate to pyruvate to form 2-oxoglutarate and alanine. The regulation of AlaAT in several plant species has been studied in response to low-oxygen stress, light and nitrogen application. In this study, induction of Arabidopsis AlaAT1 and AlaAT2 during hypoxia was observed at the transcriptional level, and an increase in enzyme activity was detected in hypoxically treated roots. In addition, the tissue-specific expression of AlaAT1 and AlaAT2 was analysed using promoter:GUS fusions. The GUS staining patterns indicated that both AlaAT genes are expressed predominantly in vascular tissues. We manipulated AlaAT expression to determine the relative importance of this enzyme in low-oxygen stress tolerance and nitrogen metabolism. This was done by analysing T-DNA mutants and over-expressing barley AlaAT in Arabidopsis. The AlaAT1 knockout mutant (alaat1-1) showed a dramatic reduction in AlaAT activity, suggesting that AlaAT1 is the major AlaAT isozyme in Arabidopsis. Over-expression of barley AlaAT significantly increased the AlaAT activity in the transgenic plants. These plants were analysed for metabolic changes over a period of hypoxic stress and during their subsequent recovery. The results showed that alaat1-1 plants accumulate more alanine than wild-type plants during the early phase of hypoxia, and the decline in accumulated alanine was delayed in the alaat1-1 line during the post-hypoxia recovery period. When alanine was supplied as the nitrogen source, alaat1-1 plants utilized alanine less efficiently than wild-type plants did. These results indicate that the primary role of AlaAT1 is to break down alanine when it is in excess. Therefore, AlaAT appears to be crucial for the rapid conversion of alanine to pyruvate during recovery from low-oxygen stress.


Formulation and Characterization of Pyrazinamide Polymeric Nanoparticles for Pulmonary Tuberculosis: Efficiency for Alveolar Macrophage Targeting.
Pyrazinamide, a highly specific agent against Mycobacterium tuberculosis is used as first-line drug to treat tuberculosis. The current work aims to formulate polymeric nanoparticles based drug delivery system to sustain the release profile and reduce the dosing frequency of pyrazinamide. Further aim was to target the macrophages within body fluid. These polymeric nanoparticles were prepared by simultaneous double-emulsion (W/O/W) solvent evaporation/diffusion technique. The prepared dispersions were characterized for various biopharmaceutical parameters such as particle size, zeta potential, polydispersity index, drug loading capacity, entrapment efficiency and targeting to alveolar macrophages. The formulated polymeric nanoparticles were in the particle size range of 45.51 to 300.4 nm with a maximum drug entrapment efficiency of 80.9%. The stability study of optimized batch conducted at 40±2°/75±5% relative humidity showed no significant changes up to 90 days. X-Ray Diffraction spectrum exhibits the transformation of crystalline form of drug to amorphous in the formulation. Scanning Electron Microscope image showed nanoparticles spherical in shape with smooth surface. In vitro release profiles were biphasic in nature with burst release followed by controlled release over a period of 24 h obeying diffusion mechanism. In vivo and ex vivo studies results of the study show significant uptake of the nanoparticles by alveolar macrophages through fluorescent micrograph. Polymeric nanoparticles formulation of pyrazinamide could encompass significant uptake by alveolar macrophages, the high first-pass metabolism, sustain the release of drug leading to reduction in dose, toxicity and improvement of patient compliance.


Differential effects of gonadotropin-releasing hormone (GnRH)-I and GnRH-II on prostate cancer cell signaling and death.
GnRH is known to directly regulate prostate cancer cell proliferation, but the precise mechanism of action of the peptide is still under investigation. This study demonstrates differential effects of GnRH-I and GnRH-II on androgen-independent human prostate cancer cells. Both GnRH-I and GnRH-II increased the intracellular Ca(2+) concentration ([Ca(2+)](i)) either through Ca(2+) influx from external Ca(2+) source or via mobilization of Ca(2+) from internal Ca(2+) stores. Interestingly, the [Ca(2+)](i) increase was mediated by activation of the ryanodine receptor but not the inositol trisphosphate receptor. Trptorelix-1, a novel GnRH-II antagonist but not cetrorelix, a classical GnRH-I antagonist, completely inhibited the GnRH-II-induced [Ca(2+)](i) increase. Concurrently at high concentrations, trptorelix-1 and cetrorelix inhibited GnRH-I-induced [Ca(2+)](i) increase, whereas at low concentrations they exerted an agonistic action, inducing Ca(2+) influx. High concentrations of trptorelix-1 but not cetrorelix-induced prostate cancer cell death, probably through an apoptotic process. Using photoaffinity labeling with (125)I-[azidobenzoyl-D-Lys(6)]GnRH-II, we observed that an 80-kDa protein specifically bound to GnRH-II. This study suggests the existence of a novel GnRH-II binding protein, in addition to a conventional GnRH-I receptor, in prostate cancer cells. These data may facilitate the development of innovatory therapeutic drugs for the treatment of prostate cancer.


Stroke patients' and carers' perception of barriers to accessing stroke information.
Education is a key component of post stroke care, but patients and carers often report dissatisfaction with information provided. A small number of studies have reported challenges surrounding the provision of information to this population, but patients' perspectives have not been explored in detail. The aim of this study was to identify patients' and carers' perceived barriers to accessing and understanding information about stroke. Interviews were conducted with patients and their carers prior to and 3 months following discharge from an acute stroke unit. Transcripts were analysed using qualitative content analysis. The three categories of barriers were identified: (1) limited availability and suitability of information, (2) barriers in the hospital environment, and (3) patient and carer barriers. Three themes were also identified, namely, (1) who is responsible, (2) communication, and (3) not knowing. These results have clinical implications for the way in which health professionals coordinate and present stroke information to patients and carers. Addressing these barriers may enhance patients' and carers' access to, understanding of, and satisfaction with information about stroke.


Decay of female sexual behavior under parthenogenesis.
A laboratory strain of Drosophila mercatorum has existed for 20 years without males and therefore without natural selection operating to maintain the genetic basis of female mating behavior. The females of this strain have recently experienced a genetic impairment of mating capacity. This observation exemplifies the mode of evolution of vestigial characters and supports Muller's theory that random mutation will tend to destroy the genetic basis of a character from which selection has been removed.


The pitx2 homeobox protein is required early for endoderm formation and nodal signaling. .
Nodal and Nodal-related factors play fundamental roles in a number of developmental processes, including mesoderm and endoderm formation, patterning of the anterior neural plate, and determination of bilateral asymmetry in vertebrates. pitx2, a paired-like homeobox gene, has been proposed to act downstream of Nodal in the gene cascade providing left-right cues to the developing organs. Here, we report that pitx2 is required early in the Nodal signaling pathway for specification of the endodermal and mesodermal germ layers. We found that pitx2 is expressed very early during Xenopus and zebrafish development and in many regions where Nodal signaling is required, including the presumptive mesoderm and endoderm at the blastula and gastrula stages and the prechordal mesoderm at later stages. In Xenopus embryos, overexpression of pitx2 caused ectopic expression of goosecoid and sox-17 and interfered with mesoderm formation. Overexpression of pitx2 in Xenopus animal cap explants partially mimics the effects of Nodal overexpression, suggesting that pitx2 is a mediator of Nodal signaling during specification of the endoderm and prechordal plate, but not during mesoderm induction. We further demonstrate that pitx2 is induced by Nodal signaling in Xenopus animal caps and that the early expression of zebrafish pitx2 is absent when the Nodal signaling pathway is inactive. Inhibition of pitx2 function using a chimeric EnR-pitx2 blocked specification of the mesoderm and endoderm and caused severe embryonic defects resembling those seen when Nodal signaling is inhibited. Following inhibition of pitx2 function, the fate of ventral vegetal blastomeres was shifted from an endodermal to a more mesodermal fate, an effect that was reversed by wild-type pitx2. Finally, we show that inhibition of pitx2 function interferes with the response of cells to Nodal signaling. Our results provide direct evidence that pitx2 function is required for normal specification of the endodermal and mesodermal germ layers.