Lung inhomogeneities, inflation and [18F]2-fluoro-2-deoxy-D-glucose uptake rate in acute respiratory distress syndrome.
The aim of the study was to determine the size and location of homogeneous inflamed/noninflamed and inhomogeneous inflamed/noninflamed lung compartments and their association with acute respiratory distress syndrome (ARDS) severity.In total, 20 ARDS patients underwent 5 and 45 cmH2O computed tomography (CT) scans to measure lung recruitability. [(18)F]2-fluoro-2-deoxy-d-glucose ([(18)F]FDG) uptake and lung inhomogeneities were quantified with a positron emission tomography-CT scan at 10 cmH2O. We defined four compartments with normal/abnormal [(18)F]FDG uptake and lung homogeneity.The homogeneous compartment with normal [(18)F]FDG uptake was primarily composed of well-inflated tissue (80±16%), double-sized in nondependent lung (32±27% versus 16±17%, p<0.0001) and decreased in size from mild, moderate to severe ARDS (33±14%, 26±20% and 5±9% of the total lung volume, respectively, p=0.05). The homogeneous compartment with high [(18)F]FDG uptake was similarly distributed between the dependent and nondependent lung. The inhomogeneous compartment with normal [(18)F]FDG uptake represented 4% of the lung volume. The inhomogeneous compartment with high [(18)F]FDG uptake was preferentially located in the dependent lung (21±10% versus 12±10%, p<0.0001), mostly at the open/closed interfaces and related to recruitability (r(2)=0.53, p<0.001).The homogeneous lung compartment with normal inflation and [(18)F]FDG uptake decreases with ARDS severity, while the inhomogeneous poorly/not inflated compartment increases. Most of the lung inhomogeneities are inflamed. A minor fraction of healthy tissue remains in severe ARDS.


Visit-to-Visit Glycemic Variability and Risks of Cardiovascular Events and All-Cause Mortality: The ALLHAT Study.
The prognostic value of long-term glycemic variability is incompletely understood. We evaluated the influence of visit-to-visit variability (VVV) of fasting blood glucose (FBG) on incident cardiovascular disease (CVD) and mortality. We conducted a prospective cohort analysis including 4,982 participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) who attended the baseline, 24-month, and 48-month visits. VVV of FBG was defined as the SD or variability independent of the mean (VIM) across FBG measurements obtained at the three visits. Participants free of CVD during the first 48 months of the study were followed for incident CVD (coronary heart disease [CHD], stroke, and heart failure [HF]) and all-cause mortality. Over a median follow-up of 5 years, there were 305 CVD events (189 CHD, 45 stroke, and 81 HF) and 154 deaths. The adjusted hazard ratio (HR) comparing participants in the highest versus lowest quartile of SD of FBG (≥26.4 vs. <5.5 mg/dL) was 1.43 (95% CI 0.93-2.19) for CVD and 2.22 (95% CI 1.22-4.04) for all-cause mortality. HR for VIM was 1.17 (95% CI 0.84-1.62) for CVD and 1.89 (95% CI 1.21-2.93) for all-cause mortality. Among individuals without diabetes, the highest quartile of SD of FBG (HR 2.67 [95% CI 0.14-6.25]) or VIM (HR 2.50 [95% CI 1.40-4.46]) conferred a higher risk of death. Greater VVV of FBG is associated with increased mortality risk. Our data highlight the importance of achieving normal and consistent glycemic levels for improving clinical outcomes.


Automatic discovery and classification of bioinformatics Web sources.
The World Wide Web provides an incredible resource to genomics researchers in the form of query access to distributed data sources--e.g. BLAST sequence homology search interfaces. The number of these autonomous sources and their rate of change outpaces the speed at which they can be manually classified, meaning that the available data is not being utilized to its full potential. Manually maintaining a wrapper library will not scale to accommodate the growth of genomics data sources on the Web, challenging us to produce an automated system that can find, classify and wrap new sources without constant human intervention. Previous research has not addressed the problem of automatically locating, classifying and integrating classes of bioinformatics data sources. This paper presents an overview of a system for finding classes of bioinformatics data sources and integrating them behind a unified interface. We describe our approach for automatic classification of new Web sources into relevance categories that eliminates the human effort required to maintain a current repository of sources. Our approach is based on a meta-data description of classes of interesting sources that describes the important features of an entire class of services without tying that description to any particular Web source. We examine the features of this format in the context of BLAST sources to show how it relates to Web sources that are being described. We then show how a description can be used to determine if an arbitrary Web source is an instance of the described service. To validate the effectiveness of this approach, we have constructed a prototype that correctly classifies approximately two-thirds of the BLAST sources we tested. We conclude with a discussion of these results, the factors that affect correct automatic classification and areas for future study.


Relationship between retinal microvascular impairment and subclinical atherosclerosis in SLE.
Patients with SLE have higher cardiovascular (CV) risk compared with healthy controls (HC) and are characterised by accelerated atherosclerosis; intima media thickness (IMT), marker of subclinical atherosclerosis, is higher in patients with SLE than in HCs. Retinal microvascular impairment detected through optical coherence tomography angiography (OCTA) was investigated as a marker of systemic vascular involvement in SLE.The aim of the study was to evaluate the relationship between retinal vascular impairment and IMT in SLE. Cross-sectional study recruiting patients with SLE and HCs. Data of the study population were collected. CV risk was evaluated through the American College of Cardiology/American Heart Association (ACC/AHA) guidelines, Framingham and QRESEARCH risk estimator V.3 (QRISK3) scores. Both groups underwent OCTA and carotid ultrasound with IMT assessment.Statistical analysis was accomplished using Pearson/Spearman, t-test/Mann-Whitney or χ2 test. Variables statistically significant at univariate regression analysis were tested in an age-corrected and sex-corrected multivariate regression model. 43 patients with SLE and 34 HCs were recruited. Patients with SLE showed higher triglycerides (p=0.019), Triglycerides-Glucose (TyG) Index (p=0.035), ACC/AHA guidelines (p=0.001), Framingham Risk Scores (p=0.008) and a reduced superficial (p<0.001) and deep (p=0.005) whole retinal vessel density (VD) compared with HCs.In SLE univariate analysis, deep whole VD showed a negative correlation with IMT (p=0.027), age (p=0.001), systolic blood pressure (p=0.011), QRISK3 Score (p<0.001), Systemic Lupus International Collaborating Clinics Damage Index (p=0.006) and apolipoprotein B (p=0.021), while a positive correlation was found with female sex (p=0.029). Age-adjusted and sex-adjusted multivariate analysis confirmed QRISK3 Score (p=0.049) and IMT (p=0.039) to be independent risk factors for reduced retinal VD. Patients with SLE showed lower retinal VD and higher CV risk indicators compared with HCs. Among patients with SLE, QRISK3 Score and IMT were found to be independent risk factors for retinal vascular impairment, suggesting a role of OCTA in evaluating preclinical CV involvement in SLE. Moreover, TyG Index could represent a biomarker of CV risk in patients with SLE compared with HCs.


Bis(oxazoline)-based coordination polymers: a recoverable system for enantioselective Henry reactions.
An efficient release-capture strategy for the recovery and reuse of enantioselective catalysts in the Henry reaction is described. This strategy is based on the precipitation of an insoluble coordination polymer at the end of each reaction, allowing easy separation from products. The coordination polymer is formed through aggregation of Cu(II) ions with ditopic bisoxazoline-based chiral ligands. Up to 11 catalytic cycles have been conducted keeping good yields and enantioselectivities.


Molecular and Functional Analysis of Trehalose-6-Phosphate Synthase Genes Enhancing Salt Tolerance in Anoectochilus roxburghii (Wall.) Lindl.
Trehalose is a reducing disaccharide, acting as a protectant against various environmental stresses in numerous organisms. In plants, trehalose-6-phosphate synthase (TPS) plays a crucial role in trehalose biosynthesis. Anoectochilus roxburghii (Wall.) Lindl. is a prominent species of the Anoectochilus genus, widely utilized as a health food. However, the functional analysis of TPS in this species has been limited. In this study, TPS genes were cloned from A. roxburghii. The ArTPS gene, with an open reading frame spanning 2850 bp, encodes 950 amino acids. Comparative and bioinformatics analysis revealed that the homology was presented between the ArTPS protein and TPSs from other plant species. The ORF sequence was utilized to construct a prokaryotic expression vector, Pet28a-ArTPS, which was then transformed into Escherichia coli. The resulting transformants displayed a significant increase in salt tolerance under the stress conditions of 300 mmol/L NaCl. Quantitative RT-PCR analysis demonstrated that the expression of ArTPS genes responded to NaCl stress. The accumulation of G6P was upregulated, whereas the content of T6P exhibited an opposite expression trend. The glycometabolism products, including trehalose, exhibited notable changes under NaCl stress, although their variations may differ in response to stimulation. The content of kinsenoside, a characteristic product of A. roxburghii, was significantly upregulated under NaCl stress. These results suggest that the ArTPS genes function in response to NaCl stimulation and play a key role in polysaccharide and glycoside metabolism in Anoectochilus. This study provides new insights into the engineering modification of the health food A. roxburghii to enhance the medicinal activity of its ingredients.


Phosphatidylinositol 3-kinase activation is required for sulfonylurea stimulation of glucose transport in rat skeletal muscle.
Sulfonylureas are drugs widely used in the treatment of patients with type 2 diabetes mellitus. In addition to their pancreatic effect of stimulating insulin secretion, many studies suggest that sulfonylureas also have extrapancreatic actions. We have previously reported that gliclazide, a second-generation sulfonylurea, stimulates the glucose uptake by rat hindquarter skeletal muscle directly and immediately by promoting the translocation of glucose transporter 4 to the plasma membrane. The aim of our study was to approach the gliclazide intracellular signaling pathway. For this purpose, we incubated clamped and isolated soleus muscle from rat with gliclazide. The following results were obtained: 1) gliclazide stimulates insulin receptor substrate (IRS)-1-phosphatidylinositol 3 (PI3)-kinase-associated activity, and this activity is necessary for gliclazide-stimulated glucose transport; 2) gliclazide treatment produces a gradual translocation of the diacylglycerol (DAG)-dependent isoforms protein kinase C (PKC) alpha, theta, and epsilon from cytosolic to membrane fraction that is dependent on PI3-kinase and phospholipase C (PLC)-gamma activation; and 3) PKC and PLC-gamma activation is necessary for gliclazide-stimulated glucose transport. We propose a hypothetical signaling pathway by which gliclazide could stimulate IRS-1 that would allow its association with PI3-kinase, promoting its activation. PI3-kinase products could induce PLC-gamma activation, whose hydrolytic activity could activate the DAG-dependent isoforms PKC alpha, theta, and epsilon.


Profiling the effects of short time-course cold ischemia on tumor protein phosphorylation using a Bayesian approach.
Phosphorylated proteins provide insight into tumor etiology and are used as diagnostic, prognostic, and therapeutic markers of complex diseases. However, pre-analytic variations, such as freezing delay after biopsy acquisition, often occur in real hospital settings and potentially lead to inaccurate results. The objective of this work is to develop statistical methodology to assess the stability of phosphorylated proteins under short-time cold ischemia. We consider a hierarchical model to determine if phosphorylation abundance of a protein at a particular phosphorylation site remains constant or not during cold ischemia. When phosphorylation levels vary across time, we estimate the direction of the changes in each protein based on the maximum overall posterior probability and on the pairwise posterior probabilities, respectively. We analyze a dataset of ovarian tumor tissues that suffered cold-ischemia shock before the proteomic profiling. Gajadhar et al. (2015) applied independent clusterings for each patient because of the high heterogeneity across patients, while our proposed model shares information allowing conclusions for the entire sample population. Using the proposed model, 15 out of 32 proteins show significant changes during 1-hour cold ischemia. Through simulation studies, we conclude that our proposed methodology has a higher accuracy for detecting changes compared to an order restricted inference method. Our approach provides inference on the stability of these phosphorylated proteins, which is valuable when using these proteins as biomarkers for a disease.


Physical Behavior Profiles in Chronic Cancer-Related Fatigue.
Increasing physical activity level is a generally effective intervention goal for patients who suffer from chronic cancer-related fatigue (CCRF). However, patients are unlikely to benefit equally from these interventions, as their behavioral starting points might vary substantially. Therefore, we explored patterns of physical behavior of participants who suffer from CCRF. Baseline data of a randomized controlled trial were used for a latent profile analysis on nine accelerometer-derived physical behavior measures, describing levels and patterns of physical activity, moderate-to-vigorous intensity physical activity (MVPA), and sedentary behavior. The relation between participant characteristics and the latent profiles was analyzed. Accelerometer data of 172 participants from the Netherlands was analyzed. Three latent profiles were distinguished that differed most on physical activity level and total time spent in MVPA. Eighty-eight percent of all participants were assigned to a profile with a probability higher than 8. Age and perceiving limitations by comorbid conditions and pain were significant covariates of profile membership. We distinguished three physical behavior profiles. The differences between the patterns indicate that the heterogeneity of this sample requires patients to have substantially different treatment goals. Further research should test the applicability of these profiles in clinical practice.


Laboratory identification and sensitivity testing of yeast isolates.
Methods used for identification and sensitivity testing of yeasts are presented. Identification depends on both morphologic features and biochemical characteristics. The germ tube test is a simple test for the identification of the commonest yeast pathogen, Candida albicans. Species not identified by this method can be identified by means of several other tests, the most important being the carbohydrate assimilation test. Several kits are commercially available and most appear to be satisfactory. Antifungal susceptibility tests are not standardized, and results are often subject to considerable variation. Until improved methods are developed, it might be advisable that smaller laboratories only do a preliminary screening test for flucytosine susceptibility and, if indicated, also for amphotericin B susceptibility. Important isolates should be sent to laboratories with a special interest in antifungal susceptibility testing for more extensive testing.


Stable angina: drugs, angioplasty or surgery?
Stable angina is a common condition with a good overall prognosis and annual mortality is 2-4%, whatever treatment is employed. Medical therapy with nitrates, beta-blockers, calcium antagonists and lipid-lowering agents is appropriate as first-line therapy in those patients not specifically identified as being at risk by exercise testing and/or angiography. Dosage should be optimized. Coronary artery bypass grafting appears to improve prognosis in those at risk when compared with medical therapy but the trials are old and do not take into account major advances in medical therapy nor the use of arterial conduits in coronary artery bypass grafting (CABG). Percutaneous transluminal coronary angioplasty (PTCA) relieves symptoms when medical therapy is ineffective but its role as an initial therapy has not been established, nor does it compare favourably with CABG with regard to the degree of revascularization and subsequent re-intervention or need for additional anti-anginal drugs. There are little substantial data on prognostic effects. PTCA is, however, less traumatic, less expensive and associated with a quicker recovery than CABG, providing a viable alternative for symptomatic (not prognostic) benefit in appropriately selected and informed patients. Medical therapy, PTCA and CABG should not be seen as competitive but complementary strategies. Optimal utilization of all three treatment modalities, either alone or in combination, can provide substantial symptomatic relief for the angina patient.


Poverty and health: the mediating role of perceived discrimination.
Social-class discrimination is evident in many societies around the world, but little is known about its impact on the poor or its role as an explanatory variable in the link between socioeconomic status and health. The current study tested the extent to which perceived discrimination explains socioeconomic gradients in physical health. Participants were 252 adolescents (51% male, 49% female; mean age = 17.51 years, SD = 1.03 years) who participated in Wave 3 of an ongoing longitudinal study focusing on the developmental consequences of rural poverty. Physical health was operationalized as allostatic load, a measure of cumulative wear and tear on the body caused by overactivation of physiological systems that respond to stress. Mediation analyses suggested that 13% of the effect of poverty on allostatic load is explained by perceived discrimination. The findings suggest that social-class discrimination is one important mechanism behind the influence of poverty on physical health.


Endothelial cell barrier regulation by sphingosine 1-phosphate.
Disruption of vascular barrier integrity markedly increases permeability to fluid and solute and is the central pathophysiologic mechanism of many inflammatory disease processes, including sepsis and acute lung injury (ALI). Dynamic control of the endothelial barrier involves complex signaling to the endothelial cytoskeleton and to adhesion complexes between neighboring cells and between cells and the underlying matrix. Sphingosine 1-phosphate (S1P), a biologically active lipid generated by hydrolysis of membrane lipids in activated platelets, organizes actin into a strong cortical ring and strengthens both intercellular and cell-matrix adherence. The mechanisms by which S1P increases endothelial barrier integrity remain the focus of intense basic research. The downstream structural changes induced by S1P interact to decrease vascular permeability to fluid and solute, which translates into a reduction lung edema formation in animal models of ALI, thus suggesting a potentially life-saving therapeutic role for vascular barrier modulation in critically ill patients.


Polyanion based controlled release system for the GnRH-receptor antagonist degarelix.
The aim of this study was to investigate the interaction between the positively charged gonadotropin releasing hormone receptor antagonist degarelix and the two polyanions alginate and carboxymethyl cellulose (CMC). Light as well as transmission electron microscopy revealed that complexes formed by simple mixing of the peptide with one of the polymers had a nano-structure consisting of twisted fibers. The remarkable unique process of complex formation could be followed by isothermal titration calorimetry: We found that peptide self-aggregates dissolved upon the addition of polyanion and peptide-polymer-complexes formed thereafter with the anionic polymer as a template. Peptide release from the complexes was tested in vitro and in vivo and compared to the dissolution of drug from self-aggregates. In vitro the release was monitored over a period of three months. We could find only slight differences in the release kinetics for the alginate and the CMC complexes compared to the pure drug. An in vivo study in Sprague Dawley rats showed similar degarelix plasma concentration levels for the complex formulations and an aqueous degarelix solution following subcutaneous injection. Overall, our findings suggest a competition between complex formation and peptide aggregation, which did not increase the availability of free drug.


Urinary excretion levels of water-soluble vitamins in pregnant and lactating women in Japan.
Recent studies have shown that the urinary excretion levels of water-soluble vitamins can be used as biomarkers for the nutritional status of these vitamins. To determine changes in the urinary excretion levels of water-soluble vitamins during pregnant and lactating stages, we surveyed and compared levels of nine water-soluble vitamins in control (non-pregnant and non-lactating women), pregnant and lactating women. Control women (n=37), women in the 2nd (16-27 wk, n=24) and 3rd trimester of pregnancy (over 28 wk, n=32), and early- (0-5 mo, n=54) and late-stage lactating (6-11 mo, n=49) women took part in the survey. The mean age of subjects was ~30 y, and mean height was ~160 cm. A single 24-h urine sample was collected 1 d after the completion of a validated, self-administered comprehensive diet history questionnaire to measure water-soluble vitamins or metabolites. The average intake of each water-soluble vitamin was ≍ the estimated average requirement value and adequate intake for the Japanese Dietary Reference Intakes in all life stages, except for vitamin B6 and folate intakes during pregnancy. No change was observed in the urinary excretion levels of vitamin B2, vitamin B6, vitamin B12, biotin or vitamin C among stages. Urine nicotinamide and folate levels were higher in pregnant women than in control women. Urine excretion level of vitamin B1 decreased during lactation and that of pantothenic acid decreased during pregnancy and lactation. These results provide valuable information for setting the Dietary Reference Intakes of water-soluble vitamins for pregnant and lactating women.


The network dynamics of self-compassion components and psychological symptoms during an intervention.
The change process of psychological interventions is complex and should be understood with a systems perspective. This study sought to examine the network dynamics of self-compassion components and psychological symptoms during an intervention. A total of 139 participants completed daily assessments during a 28-day intervention. Utilizing multilevel vector autoregressive (VAR) model, temporal and contemporaneous networks were generated and group differences in network dynamics were evaluated through descriptive assessment and permutation tests. The intervention group displayed a significant increase in self-compassion and decrease in psychological symptoms, with self-compassion mediating the intervention effects on symptoms. Network analysis revealed some network dynamics that might be relevant to desirable therapeutic changes in the intervention group. The intervention group demonstrated a significantly less connected contemporaneous depression network, indicating a decreased vulnerability to symptom activation. Additionally, the intervention group showed significantly more temporal connections from self-compassion to anxiety, indicating an increased influence of self-compassion on anxiety. These findings suggest that the intervention may have reshaped the interconnection pattern of symptoms and that between self-compassion components and symptoms.


[Epidemiology and risk factors of breast cancer].
A major public health issue, breast cancer affects 53000 women each year in France. The leading cause of cancer deaths in women, its risk factors are numerous and include age, early puberty and/or late menopause, later age at first pregnancy as well as a family history of the disease.


Early pneumotoxic effects after oral administration of 1,2-dichloroethane.
Early biochemical and histological changes in rat lungs were investigated after oral administration of 136 mg/kg 1,2-dichloroethane in oleum solution. The experiment was performed using 80 male Wistar rats. Bronchoalveolar lavage fluid and lung homogenate were examined on posttreatment days 1, 5, 15, and 30. In bronchoalveolar lavage fluid, the activities of lactate dehydrogenase, alkaline phosphatase, and acid phosphatase were elevated on day 1. The activities of superoxide dismutase, catalase, and glutathione peroxidase, and the content of malondialdehyde in lung homogenate, were also increased on day 1. The histological investigation indicated congestion, edema, and lung interstitial inflammatory changes. It was concluded that oral administration of 1,2-dichloroethane causes mild-to-moderate transitory toxic injury of the lung. Lipid peroxidation and the levels of key antioxidant enzymes are increased in the earliest posttreatment period.


[How to describe indoor environment in epidemiological studies dealing with respiratory diseases].
Indoor environment can be partly responsible for respiratory health. The aim of this paper is to summarize epidemiological studies dealing with the relations between indoor pollutions and asthma or atopy, to analyze the ways of characterization of the dwellings and to expose health effects of the studied risk factors and results of the confrontation between data issued from questionnaires and from environmental measurements. Thirty two papers were listed on Medline data base since 1990. These are mainly case-control studies and cross-sectional surveys and most often concern children. The health status is objectively evaluated by medical examinations or indirectly characterized by questionnaires on symptoms. All the studies use a questionnaire to describe indoor environment while some environmental measurements, mostly of biological pollutions, could be realized simultaneously. Some associations between different characteristics of the dwellings and respiratory symptoms are commonly found. Thus, exposure to allergens of the dwellings, environmental tobacco smoke, home dampness or characteristics and cleaning of the bedding increase the prevalence of respiratory symptoms. Residential exposure to chemical pollutants, due to the existence of recent paints are also related to different respiratory symptoms. By contrast, for other indoor risk factors, without standardized evaluation, the impact on respiratory health is inconstant. These factors are sociodemographic environment, heating and cooking installations, use of a humidifier, treatment air system or ventilation system, wall-to-wall carpets or pets at home. On examining this review literature, disparity in description of the indoor environment, depending on the studied pollutants, is pointed out. That is why we advice to use ever validated questionnaires to evaluate environmental tobacco smoke, home dampness and presence of pets, in association with environmental measurements to study indoor sources of allergens. Conversely, to evaluate the home exposure to chemical pollutions poorly studied today, some new questionnaires have to be elaborated and validated with regard to environmental measurements before being used in epidemiological studies.


The application of acute oral toxicity computational models in dangerous goods classification.
Acute oral toxicity (AOT) data inform the acute toxicity potential of a compound and guides occupational safety and transportation practices. AOT data enable the categorization of a chemical into the appropriate AOT Globally Harmonized System (GHS) category based on the severity of the hazard. AOT data are also utilized to identify compounds that are Dangerous Goods (DGs) and subsequent transportation guidance for shipping of these hazardous materials. Proper identification of DGs is challenging for novel compounds that lack data. It is not feasible to err on the side of caution for all compounds lacking AOT data and to designate them as DGs, as shipping a compound as a DG has cost, resource, and time implications. With the wealth of available historical AOT data, AOT testing approaches are evolving, and in silico AOT models are emerging as tools that can be utilized with confidence to assess the acute toxicity potential of de novo molecules. Such approaches align with the 3R principles, offering a reduction or even replacement of traditional in vivo testing methods and can also be leveraged for product stewardship purposes. Utilizing proprietary historical in vivo AOT data for 210 pharmaceutical compounds (PCs), we evaluated the performance of two established in silico AOT programs: the Leadscope AOT Model Suite and the Collaborative Acute Toxicity Modeling Suite. These models accurately identified 94% and 97% compounds that were not DGs (GHS categories 4, 5, and not classified (NC)) suggesting that the models are fit-for-purpose in identifying PCs with low acute oral toxicity potential (LD50 >300 mg/kg). Utilization of these models to identify compounds that are not DGs can enable them to be de-prioritized for in vivo testing. This manuscript provides a detailed evaluation and assessment of the two models and recommends the most suitable applications of such models.


Day admission for thoracic aortic surgery.
Elective cardiac surgical patients can be admitted on the morning of the operation. The day admission surgery is safe with optimal care for patients and provides an economical benefit. In our institution if immediate surgery is not required, patients are entered into program for serial follow up. An elective aortic intervention for open surgical or endovascular surgery is recommended when the risk of aortic rupture outweighs the risk of surgery. Patients are seen 3 to 7 days prior of day admission surgery in preoperative clinic. On the morning of surgery, the patient undergoes a reassessment to ensure no interval changes have occurred. We hereby describe our three years experience with 350 patients were referred from the Aortic Aneurysm Surveillance Program. We believe that not only patients, but all medical personal benefit from a complete preoperative evaluation of these complicated patients and this creates harmony during the entire hospitalization!


Reclamation of Cr-contaminated or Cu-contaminated agricultural soils using sunflower and chelants.
Chromium (Cr) and copper (Cu) are pollutants with a strong environmental impact. "Green biotechnology" as phytoremediation represents a sustainability opportunity for soil reclamation. In this study, we evaluated the possibility to reclaim agricultural soils located in the Solofrana valley, contaminated by Cr or Cu. Chromium contamination derives by repeated flooding events of Solofrana rivers containing Cr because of leather tanning plants, while Cu soil pollution was due to the use of Cu-rich pesticides in agriculture. Both metals showed a very low bioavailability. In order to perform an assisted phytoremediation of polluted fields, we carried out a preliminary ex situ experimentation testing for the first time sunflowers (cv. Pretor) and chelants (ethylenediaminetetraacetic acid (EDTA) and/or ethylene diamine disuccinate (EDDS)), useful when metal bioavailability is low. No symptoms of toxicity were observed in sunflowers grown on both soils, while biomass was improved when EDDS was added. Cr and Cu bioavailability was only slightly enhanced by chelants at the end of the treatments. Both Cr and Cu were mainly accumulated in the roots; moreover, Cu was also translocated to the aboveground organs in the presence of EDTA. The ex situ experimentation demonstrated that assisted phytoremediation is a very slow process not useful in the case of persistent pollution.


Ex vivo expansion of human cord blood hematopoietic progenitor cells using glutaraldehyde-fixed human bone marrow stromal cells.
Human stromal cells were immortalized and fixed with glutaraldehyde to support an ex vivo expansion of human cord blood hematopoietic progenitor cells. In addition, this enabled glutaraldehyde-fixed stromal cells to be stored at 4 degrees C. Although freeze-dried glutaraldehyde-fixed stromal cells did not increase the number of the progenitor cells, the percent decrease in the number of CD34(+) cells in the presence of freeze-dried glutaraldehyde-fixed stromal cells was less than that in the absence of the stromal cells. Thus, glutaraldehyde-fixed stromal cells can serve as a stabilizing device for hematopoietic cell expansion.


Xanthine oxidase inhibits transmembrane signal transduction in vascular endothelial cells.
The effect of xanthine oxidase (XO)-mediated oxidant stress on endothelial cell signal transduction was determined in bradykinin-stimulated cells loaded with the Ca+(+)-sensitive probe fura-2. Calf pulmonary artery endothelial cells were incubated with a reaction mixture containing XO (50 mU/ml) and its substrate, hypoxanthine (HX) (0.5 mM), for periods of 0.5 to 2.0 hr. HX/XO time dependently increased basal cytosolic free Ca++ ([Ca++]i) and decreased the response of [Ca++]i to bradykinin, so that incubation of cells with HX/XO for 1.5 hr or longer eliminated responsiveness to agonist. In presence of XO, HX dose dependently increased basal [Ca++]i (EC50 approximately 3 x 10(-5) M) and decreased the response of [Ca++]i to bradykinin. Sequential application of bradykinin and Ca++ to cells suspended in Ca+(+)-free/EGTA buffer was performed to characterize the effects of HX/XO on receptor-activated Ca++ entry and release of Ca++ from internal stores. HX/XO attenuated internal store Ca++ release and inhibited the bradykinin-stimulated Ca++ influx pathway in a time-dependent manner. When the HX dose was decreased by an order of magnitude, HX/XO selectively inhibited the agonist-stimulated influx pathway with little effect on internal store Ca++ release. Coincubation with superoxide dismutase tended to potentiate the effects of HX/XO, whereas catalase provided almost complete protection. Similar results to HX/XO-induced alterations in Ca++ signaling were observed when glucose-glucose oxidase (G/GO) was used as the oxidant-generating system. Inhibition of Ca++ signaling by HX/XO and G/GO occurred in the absence of decreased cell viability. Together, these results suggest that HX/XO-induced inhibition of signal transduction in endothelial cells is a function of H2O2-mediated oxidant stress and represents an early dysfunction in the process of oxidant injury.


Preliminary observations on expression of transforming growth factors beta1 and beta3 in equine full-thickness skin wounds healing normally or with exuberant granulation tissue.
To determine whether transforming growth factor (TGF)-beta1 and -beta3 expression differs between equine limb wounds healing normally and those healing with experimentally induced exuberant granulation tissue (EGT). Six wounds were created on the lateral aspect of both metacarpi of each horse; one forelimb was untreated, and the other was bandaged to stimulate the development of EGT. Sequential wound biopsies allowed comparison of growth factor expression between the two types of wound. Four horses (2 to 4 years of age; 350 to 420 kg). Wounds were assessed grossly, histologically, and by enzyme-linked immunosorbent assay (ELISA) for TGF-beta1 and -beta3 expression at 12 and 24 hours and 2, 5, 10, and 14 days postoperatively. Bandaged wounds developed EGT. In all wounds, TGF-beta1 peaked early and remained elevated at 14 days. Peak TGF-beta1 concentration was higher in wounds with EGT, but not significantly so. Expression of TGF-beta3 differed from TGF-beta1, with peak TGF-beta3 concentrations being delayed. Concentrations of TGF-beta3 were higher in wounds healing normally, but this difference was not significant. During both normal and exuberant wound repair, the expression of TGF-beta1 occurred earlier than TGF-beta3 expression. Wounds healing with EGT tended to have higher concentrations of fibrogenic TGF-beta1 and lower concentrations of antifibrotic TGF-beta3 than wounds healing normally, although these differences were not statistically significant. This study suggests that the production of EGT in bandaged wounds may be related to increased expression of fibrogenic TGF-beta1 and decreased expression of antifibrotic TGF-beta3. Further investigation of the roles of TGF-beta1 and -beta3 may be important in understanding the molecular control of EGT in horses.


[Health and living conditions: reflections around an attempt for a multiple and sectoral approach].
There is consensus amongst community members, local practitioners and policy and decision makers on the need for an inter-sectoral approach to health, environment and living conditions. The author analyses the processes of linking various sectors involved in six health and environment projects developed at the local or regional level in Brussels-Capital. The question of inter-sectoral collaboration is addressed differently at the regional and local levels. This question is also dealt with according to the underpinning conceptual framework of a given project. Three conceptual frameworks were identified, each reflecting the processes of knowledge development or action from the sector having initiated the project. Each framework is characterised by a clear demarcation between the fields of health and habitation and a particular linking between these two fields and other aspects of life. The sector initiating the project imposes its own model, logic and expertise, which then leads to difficulties in ensuring active participation of the other sectors implicated. The linkage of vertical or specialised approaches and broad, general ones is too often solely reduced to the integration of specialised aspects into all purpose actions. The analysis of the different projects demonstrates the lack of awareness by specialists, in this case being environmental, of the composition and complexity of the interaction between multiple aspects of life when trying to link with other sectors. Finally, the viable preservation and continuation of overarching, universal approaches are impeded by the lack of recognition and absence of funding for interventions which aim at affecting multiple aspects of life.


High-contrast, all-optical switching in bacteriorhodopsin films.
We report experiments with nonlinear-absorption-based, high-contrast, all-optical switching in photochromic bacteriorhodopsin (BR) films. The switching action is accomplished by control of the transmission of a weak probe beam through a BR sample with the help of strong pump beam illumination at 532 nm wavelength. We found that the switching properties of BR films depend on several experimentally controllable parameters such as probe wavelength, pump beam intensity, and excitation rate. A comparative study of the switching behavior and other parameters of practical use was carried out at three probe wavelengths (543, 594, and 633 nm) and various beam powers and pump excitation rates. The results are presented for commercially available wild-type and D96N variant BR films.


Open-label phase II to evaluate the efficacy of NEoadjuvant dose-dense MVAC In cOmbination with durvalumab and tremelimumab in muscle-invasive urothelial carcinoma: NEMIO.
Neoadjuvant cisplatin-based chemotherapy (NAC) is the standard of care in localized muscle-invasive bladder cancer (MIBC). However, 60-70% of patients have residual tumor after NAC. Based on the overall response rate observed in the metastatic setting, ddMVAC is the most commonly used NAC regimen in Europe. The emergence of immune checkpoint inhibitor (ICI) in the metastatic setting raises the question if the combination of chemo plus ICI could increase the pCR rate. NEMIO is a French open-label randomized phase I/II trial assessing in the neoadjuvant setting the combination of ddMVAC plus durvalumab alone or with tremelimumab: 4 cycles of ddMVAC/2 weeks + 2 cycles of Durvalumab +/- Tremelimumab/4 weeks. Cystectomy is performed 4-8 weeks after the last dose of ddMVAC. Six pts will be included in each arm in a safety run-in cohort to evaluate the toxicity rate. Each arm will be expanded to a maximum of 60 pts. The primary endpoint of the safety run-in phase will be the rate of grade 3/4 treatment-related adverse events G3/4 TRAE. The primary endpoint of the phase II will be the pathological response rate and G 3/4 TRAE. Exploratory endpoints will include biomarkers of response and resistance to the combo. A total of 120 patients will be included in 15 French centers and we expect the recruitment to be completed in 2021. NEMIO trial will assess for the first time the tolerance and the efficacy of ddMVAC regimen associated with checkpoints inhibitors as neoadjuvant treatment in localized MIBC. NCT number: NCT03549715. Registered on June 8, 2018.


The role of vibration in tactile speed perception.
The relative motion between the surface of an object and our fingers produces patterns of skin deformation such as stretch, indentation, and vibrations. In this study, we hypothesized that motion-induced vibrations are combined with other tactile cues for the discrimination of tactile speed. Specifically, we hypothesized that vibrations provide a critical cue to tactile speed on surfaces lacking individually detectable features like dots or ridges. Thus masking vibrations unrelated to slip motion should impair the discriminability of tactile speed, and the effect should be surface-dependent. To test this hypothesis, we measured the precision of participants in discriminating the speed of moving surfaces having either a fine or a ridged texture, while adding masking vibratory noise in the working range of the fast-adapting mechanoreceptive afferents. Vibratory noise significantly reduced the precision of speed discrimination, and the effect was much stronger on the fine-textured than on the ridged surface. On both surfaces, masking vibrations at intermediate frequencies of 64 Hz (65-μm peak-to-peak amplitude) and 128 Hz (10 μm) had the strongest effect, followed by high-frequency vibrations of 256 Hz (1 μm) and low-frequency vibrations of 32 Hz (50 and 25 μm). These results are consistent with our hypothesis that slip-induced vibrations concur to the discrimination of tactile speed.


Spatial and Seasonal Variation in a Reservoir Sedimentary Microbial Community as Determined by Phospholipid Analysis.
Sediment samples were collected monthly from Acton Lake, a eutrophic reservoir located in an agricultural region of southwestern Ohio, from three stations (River, Middle, and Dam) during the period May 1995 through January 1997. Sedimentary microbial biomass and community structures from these stations were studied using phospholipid analysis. At the River and Middle stations, the water column remained aerobic throughout the year, whereas the water overlying the Dam station sediments became anaerobic during summer stratification. Sedimentary microbial biomass at the River and Middle stations, as measured by the phospholipid phosphate (PLP) method, ranged from 225 to 450 nmol PLP g?1 d.w. (dry weight). Sedimentary microbial biomass at the Dam station was typically greater and ranged from 500 to 1,500 nmol PLP g?1 d.w. Principal component analysis of phospholipid fatty acid (PLFA) profiles indicated that the sedimentary microbial communities at all three stations displayed seasonal patterns of change. Among these patterns of change was a shift from aerobic microorganisms during times of cold water to anaerobic microorganisms during times of warm water. The Dam station differed from the River and Middle stations in that sediments from this station had disproportionately more polyenoic fatty acids, whereas sediments from the River and Middle stations had disproportionately more bacterial fatty acids. These data suggest that the Dam station may be a depositional zone for microeukaryotic phytoplankton produced in the overlying water column. These findings have implications for the understanding of carbon flux in reservoirs and preservation of organic matter in aquatic systems.


IL-1 receptor blockade alleviates endotoxin-mediated impairment of renal drug excretory functions in rats.
The aim of our study was to investigate whether two potent anti-inflammatory agents, dexamethasone and anakinra, an IL-1 receptor antagonist, may influence acute kidney injury (AKI) and associated drug excretory functions during endotoxemia (LPS) in rats. Ten hours after LPS administration, untreated endotoxemic rats developed typical symptoms of AKI, with reduced GFR, impaired tubular excretion of urea and sodium, and decreased urinary excretion of azithromycin, an anionic substrate for multidrug resistance-transporting proteins. Administration of both immunosuppressants attenuated the inflammatory response, liver damage, AKI, and increased renal clearance of azithromycin mainly by restoration of GFR, without significant influence on its tubular secretion. The lack of such an effect was related to the differential effect of both agents on the renal expression of individual drug transporters. Only dexamethasone increased the urinary clearance of bile acids, in accordance with the reduction of the apical transporter (Asbt) for their tubular reabsorption. In summary, our data demonstrated the potency of both agents used for the prevention of AKI, imposed by endotoxins, and for the restoration of renal drug elimination, mainly by the improvement of GFR. The influence of both drugs on altered tubular functions and the expression of drug transporters was differential, emphasizing the necessity of knowledge of transporting pathways for individual drugs applied during sepsis. The effect of anakinra suggests a significant contribution of IL-1 signaling to the pathogenesis of LPS-induced AKI.


Synthesis of RNA in mammalian cells during mitosis and interphase.
Chinese hamster cells in the mitotic and G(1) phases of the growth cycle were incubated for 30 or 60 min in suspension tissue culture and pulse-labeled with tritiated uridine. After appropriate chases, washes, and extractions, it was found that all incorporation into the nucleic acid may be accounted for by those cells in interphase. An average of 410 counts was found for incorporation into the cell population (approximately 2.0 x 10(5) cells) of which over 80% of the cells was initially in mitosis. The increasing number of cells leaving mitosis and entering interphase during the 30 min incubation was theoretically able to account for 470 counts. In addition, short-pulse labeling experiments have shown a consistent linear relationship between the percentage of cells in division and the incorporation of the isotope, which strongly suggests that, if 100% of the cells were in mitosis, the counts would be essentially zero. Thus, the entire label may be attributed to those cells in interphase where portions of the chromosomal material are known to be already extended.


Early Optimistic Effect in Periodontology and Implant Dentistry Trials.
Differences in effect estimates between early primary trials included in a meta-analysis and the pooled estimate of meta-analysis might indicate potential novelty bias. The objective of this study was to assess the presence of novelty bias in a sample of studies published in periodontology and implant dentistry. On August 7, 2020, we searched the PubMed database for meta-analyses of clinical studies published between August 2015 and August 2020. Meta-analyses with at least 4 primary studies were selected for assessment. We fitted logistic regression models using trial characteristics as predictors to assess the association between these characteristics and 1) the odds of the first trial's estimate to be included in the meta-analysis confidence interval (CI) and 2) the odds of overlap between the first trial's CI and the meta-analysis prediction interval (PI). Ninety-two meta-analyses provided data for assessment. In absolute values, 70% of the meta-analyses have a pooled estimate smaller than the corresponding estimate of the first trial, although there was overlap of the CI of estimates from the first trial and the meta-analysis in 87% of the cases. This is probably due to the small number of trials in most meta-analyses and the subsequently large uncertainty associated with the pooled effect estimate. As the number of trials in the meta-analysis increased, the odds of the treatment effect estimate of the first trial to be included in the meta-analysis CI decreased by 15% for every additional trial (odds ratio, 0.85; 95% CI, 0.73 to 0.96). Meta-analytic effect estimates appear to be more conservative than those from the first trial in the meta-analysis. Our findings show evidence of novelty bias in periodontology and implant dentistry; therefore, clinicians should be aware of the risk of making decisions based on the information reported in new trials because of the risk of exaggerated estimates in these trials.


Fetal electrocardiogram: ST waveform analysis in intrapartum surveillance.
ST waveform analysis of fetal electrocardiogram (ECG) for intrapartum surveillance (STAN) is a newly introduced method for fetal surveillance. The purpose of this commentary is to assist in the proper use of fetal ECG in combination with cardiotocography (CTG) during labour. Guidelines and recommendations concerning CTG and ST waveform interpretation and classification are stated that were agreed on by the European experts on ST waveform analysis for intrapartum surveillance during a meeting in Utretcht, The Netherlands in January 2007.


Rhino-Cerebral Aspergillosis in an Immunocompetent Patient.
Rhino-cerebral aspergillosis is a rare phenomenon describing a contiguous spread of Aspergillus species from the paranasal sinuses to the intracranial space. In this case report, we describe a case of invasive rhino-cerebral aspergillosis arising in the setting of prolonged intranasal steroid use in an 81-year-old patient with chronic sinusitis. This case report emphasizes the importance of recognizing steroid use as a risk factor for invasive aspergillosis in otherwise immunocompetent individuals.


Spectratyping of TCRs expressed by CTL-infiltrating minor histocompatibility antigen-disparate allografts.
Minor histocompatibility Ags (HA) play prominent roles in stimulating allograft rejection and are recognized by CTLs that mediate this process. However, there is no information on the diversity of TCRs that are specific for single minor histocompatibility Ag peptides and expressed by CTLs in vivo. We have used the technique of spectratyping to study the diversity of Vbeta usage and beta complementarity-determining region 3 (CDR3) length of TCRs expressed by CTL-infiltrating skin allografts expressing the immunogenic H4 peptide during the process of rejection. Spectratyping revealed overall reduction in diversity of both Vbeta usage and CDR3 length, with sequential application of primary, second-set, and third-set H4-incompatible grafts. This dissection of the array of beta-chains expressed by graft-infiltrating CTLs allowed the direct sequencing of individual beta-chain PCR products. Beta CDR3s were characterized by a net negative charge, as we have observed previously with CDR3s expressed by H4-specific CTL clones selected in vitro. Identical and closely related CDR3 amino acid sequences could be identified that were shared by TCRs that 1) utilized different Vbeta genes, 2) derived from different mice, or 3) derived from different sequential sets of allografts on individual mice. Furthermore, a number of CDR3 sequences expressed by graft-infiltrating CTLs were identical or closely related to sequences we have identified previously in in vitro selected CTL clones that were specific for the H4 peptide.


The mucosal adjuvant effect of plant polysaccharides for induction of protective immunity against Helicobacter pylori infection.
Some plant polysaccharides (PPSs) had been used as the adjuvants for systemic vaccination. In this study, we investigated whether PPSs could exhibit adjuvant effect at the mucosa. Groups of mice were intranasally immunized with Epimedium Polysaccharide (EPS), Trollius chinensis polysaccharide (TCPS), Siberian solomonseal rhizome polysaccharide (SSRPS) and Astragalus polysaccharides (APS) together with ovalbumin (OVA). Significantly higher levels of OVA-specific IgG in serum and secretory IgA in saliva, vaginal wash and intestinal lavage fluid were induced after immunization with OVA plus one of the four PPSs compared to OVA alone. Antigen absorption and TLR2 (Toll-like receptor 2) activation may be related to their mucosal adjuvant effect. Of note, when APS used as an adjuvant, intranasally vaccination with recombination UreB (rUreB, Urease subunit B) conferred more robust protection against Helicobacter pylori (H. pylori). Immunized with rUreB in combination APS resulted in mixed specific Th1 and Th17 immune response, which may contribute to the inhibition of H. pylori colonization. Though specific Th2-dominant responses were elicited when the other three PPS intranasally immunized with rUreB, no significant difference in the protective effect were found between those groups and rUreb alone group. Taken together, the four PPSs may be promising candidates for mucosal adjuvant, and APS could enhance rUreB-specific protective immunity against H. pylori infection.


A 365-day view of the difficult patients treated in an Australian adult burn center.
Although the effect of burns on mental health has been well examined, the aims of this study were to determine the prevalence of pre-existing mental health, drug and alcohol, and forensic problems in an Australian burn patient population; examine differences between these groups in terms of burns characteristics and healing; and also establish any patterns of presentation amongst these groups. Retrospective case notes of all the acute burn admissions, 273 patients, into a busy tertiary adults burn center in a full year were reviewed. Almost half of the patients admitted had underlying complex issues. Those with psychotic, forensic, and/or drug and alcohol problems tended to stay longer in hospital and required more procedures, despite burn sizes comparable with those in the general population. These patients also tended to sustain their burn injuries, and present to hospital, on a Saturday, Sunday, or Monday, rarely coming later in the week. Those with depression/anxiety had similar lengths of stay, number of procedures and random temporal presentations to the general burns population. Burn centers should be well staffed and educated in how to deal with patients with complex needs; this staffing should be actively structured to deal with a clear pattern of presentation over the weekend and Monday.


Unraveling the Complex Interplay of Phase Transitions in Spinel Ferrites: A Comprehensive Quantum Mechanical Vibrational Study of ZnFe2O4.
The rich phase transition landscape of spinel ferrites and its profound impact on their physical properties have garnered significant interest in recent years. The complex interplay of divalent and trivalent cations distributed across A- and B-sites gives rise to a captivating variety of interactions. In this study, we delve into the structural, electronic, magnetic, and vibrational properties of ZnFe2O4 as a function of the degree of inversion, employing first-principles density functional theory with global and range-separated hybrid functionals and a local basis set. The ground state of ZnFe2O4 is an open-shell system, characterized by Zn atoms occupying tetrahedral sites, Fe atoms residing in octahedral sites, and Fe atom spins exhibiting ligand parallel alignment. In the normal structure, the antiparallel arrangement is less stable than the ferro arrangement by 0.058 eV (673 K) for fully relaxed structures, decreasing to 0.034 eV (395 K) upon incorporating a zero-point vibrations contribution. For normal ferromagnetic ZnFe2O4, we calculated scattering for A1g, Eg, and 3T2g symmetry at 676.6, 367.1, and (189.7, 457.7, 602.3) cm-1, respectively. Additionally, four T1u vibrational frequencies predicted by group theory were obtained at 524.59, 358.48, 312.49, and 192.9 cm-1, demonstrating excellent agreement with the experimental studies. We also explored the influence of spin rearrangement and inversion (X = 0.5 and 1) on Raman and infrared spectra. By analyzing the infrared spectra of isotopic substitutions, we reevaluated the assignments of the four T1u modes in light of available experimental data. Notably, the sensitivity of peak positions and intensities for some Raman modes, particularly A1g and T2g(2), to spin arrangement could provide a convenient experimental tool for detecting phase transitions induced by changes in temperature or external electric fields. This investigation shines a light on the complex interplay of phase transitions in spinel ferrites, paving the way for a deeper understanding of their properties and potential applications.


Characterization of two hepatitis B virus populations isolated from a hepatitis B surface antigen-negative patient.
In a study of surface antigen-negative, but weakly hepatitis B virus (HBV) DNA-positive, patients, we were able to amplify and clone whole HBV genomes from the serum of a cirrhotic patient. Sequencing showed that the patient harbored two different HBV populations, one of genotype A and the other of genotype D, with the genotype D genome apparently predominating. The surface antigen of the genotype A virus is heavily mutated, especially in the extracellular << determinant a >> region, with several mutations that have not been previously described. The genotype D virus is a precore mutant. Both genomes possess the common A1762T-G1764A double mutation of the basal core promoter (BCP), and the genotype D virus is also mutated in the << TATA box >> of the large surface antigen promoter. Biological characterization showed that the genotype A genome was fully replication-competent, whereas the genotype D genome replicated poorly. The small surface antigen of the genotype A virus was only very weakly recognized by commercial tests. The small surface antigen of the genotype D virus could be recognized by the tests, but it was mainly retained within transfected cells, probably because of an excess of large surface antigen. In conclusion, the cryptic nature of this double HBV infection is characterized by the predominance of the replication-deficient genotype D virus over the replication-competent genotype A virus.


Is there an alternative to the surgical above-knee bypass in treatment of superficial femoral artery disease? Experiences with Viabahn stent graft.
We conducted a retrospective study to compare short- and mid-term patencies of Viabahn with surgical above-knee prosthetic bypass (pAKB). The records of 52 patients with either pAKB (n = 25) or Viabahn (n = 27) were reviewed. The majority had Rutherford clinical grade 3. Patients were followed after 3, 6, and 12 months and yearly thereafter. For Viabahn, the short-term (1-16 months) primary patency rate was 60% with a secondary patency rate of 90%, and mid-term (1-68 months) patencies of 47% and 83.3%, respectively. In pAKB, the short-term results revealed a primary patency rate of 78% with a secondary patency of 91% and mid-term results of 65% and 90%, respectively. No statistical difference was found concerning short-term patencies. Mid-term primary patency was lower for Viabahn (P < .05) and secondary patency proved no significant difference. Viabahn revealed similar short-term primary and secondary patencies but lower mid-term primary patency. It provides a good alternative therapy to pAKB.


Highly efficient piezotronic strain sensors with symmetrical Schottky contacts on the monopolar surface of ZnO nanobelts.
Piezotronic strain sensors have drawn a lot of attention since the piezotronic theory was established. In this work, we developed a flexible piezotronic strain sensor based on an indium-doped ZnO nanobelt, of which the top surface was the monopolar surface. By connecting two electrodes with the two ends of the top surface of the nanobelt, the strain sensor was constructed. Compared with a nanorod/nanowire based strain sensor, this monopolar surface device avoids the need to identify the polar direction. Under strain, a static potential with the same value and polarity was generated by the coupling effect of the piezoelectric effect and the Poisson effect. This induced piezopotential influenced the Schottky barrier heights at the interfaces of both the source and drain electrodes, resulting in current changes with the same trend at forward and reverse biases. By applying a series of periodical strains, the sensor showed clear, fast and accurate current responses. The gauge factor achieved for compressive strain was 4036. This type of piezotronic strain sensor with a polar surface facing upward presented a high performance and easier fabrication, showing promise for applications in electrical mechanical sensors and MEMS.


Oral Administration of Glucosylceramide Suppresses Tumor Growth by Affecting the Ceramide/Sphingosine-1-Phosphate Balance in Breast Cancer Tissue.
Ceramide and sphingosine-1-phosphate (S1P) play opposing roles in cell death and survival, and maintain a dynamic balance called the sphingolipid rheostat. Glucosylceramide is a substrate to generate ceramide but its effect on breast cancer by oral administration was never tested. The purpose of this study was to reveal the anticancer activity of glucosylceramide and its potential as a new therapeutic agent in breast cancer. E0771 cells were inoculated into the breast tissue of female C57BL/6NJcl mice. Glucosylceramide was administered orally to the mice for nine consecutive days. The concentrations of sphingolipid mediators including ceramide, glucosylceramide, and S1P in tumor tissues and serum were determined by mass spectrometry. Oral administration of glucosylceramide significantly suppressed E0771 tumor growth compared with the control group (P = 0.006). There were no significant differences in the serum concentrations of sphingolipid mediators including ceramide and S1P between the mice treated with glucosylceramide and control-treated mice. The ceramide concentration was significantly lower in tumor tissues (P = 0.026), and the S1P concentration was significantly higher than that in paired non-tumor tissues (P = 0.009). The S1P concentration in tumor tissues was significantly lower in mice treated with glucosylceramide than in control-treated mice (P = 0.001). The ceramide-to-S1P concentration ratio in tumor tissues was significantly higher in mice treated with glucosylceramide than in control-treated mice (P = 0.034). Breast tumors could enhance their survival by increasing S1P conversion from ceramide. Oral administration of glucosylceramide suppressed tumor growth by affecting the ceramide/S1P balance. Oral administration of glucosylceramide is a promising basis for a new therapeutic approach.


Prognostic Immune Effector Signature in Adult Acute Lymphoblastic Leukemia Patients Is Dominated by γδ T Cells.
The success of immunotherapy has highlighted the critical role of the immune microenvironment in acute lymphoblastic leukemia (ALL); however, the immune landscape in ALL remains incompletely understood and most studies have focused on conventional T cells or NK cells. This study investigated the prognostic impact of circulating γδ T-cell alterations using high-dimensional analysis in a cohort of newly diagnosed adult ALL patients (10 B-ALL; 9 Philadelphia+ ALL; 9 T-ALL). Our analysis revealed common alterations in CD8+ T cells and γδ T cells of relapsed patients, including accumulation of early stage differentiation and increased expression of BTLA and CD73. We demonstrated that the circulating γδ T-cell signature was the most discriminating between relapsed and disease-free groups. In addition, Vδ2 T-cell alterations strongly discriminated patients by relapse status. Taken together, these data highlight the role of ɣδ T cells in adult ALL patients, among whom Vδ2 T cells may be a pivotal contributor to T-cell immunity in ALL. Our findings provide a strong rationale for further monitoring and potentiating Vδ2 T cells in ALL, including in the autologous setting.


Map locations of mouse hepatitis virus temperature-sensitive mutants: confirmation of variable rates of recombination.
Using standard genetic recombination techniques, studies in our laboratory suggest that recombination rates are very high and vary in different portions of the mouse hepatitis virus (MHV) genome. To determine the actual recombination frequencies in the MHV genome and localize the nucleotide boundaries of individual viral genes, we have sequenced temperature-sensitive and revertant viruses to identify the location of specific mutant alleles. Complementation group F RNA+ ts mutants (LA7, NC6, and NC16) each contained a unique mutation which was tightly linked to the ts phenotype and resulted in a conservative or nonconservative amino acid change in the MHV S glycoprotein gene. In agreement with previous recombination mapping studies, the mutation in LA7 and NC6 mapped within the S1 domain while NC16 mapped within the S2 domain. To determine the map coordinates of the MHV polymerase genes, several RNA- mutants and their revertants belonging to complementation groups C (NC3 and LA9) and E (LA18 and NC4) were also sequenced. Mutations were identified in each virus that were tightly linked to the ts phenotype and resulted in either a conservative or nonconservative amino acid change. The group C allele spanned the ORF 1a/ORF 1b junction, while the group E mutants mapped at the C terminus of ORF 1b about 20 to 22 kb from the 5' end of the genome. Mutation rates, calculated from the reversion frequencies of plaque-purified ts viruses requiring a single nucleotide alteration for reversion, approached 1.32 (+/- 0.89) x 10(-4) substitutions per nucleotide site per round of template copying. Detailed recombination mapping studies across known distances between these different ts alleles has confirmed that homologous recombination rates approached 25% and varied within different portions of the MHV genome.


Profiling bioactive flavonoids and carotenoids in select south Indian spices and nuts.
The objective of this study was to examine the bioactive flavonoids and carotenoids concentration in fifteen south Indian spice and two tree nut species using high performance liquid chromatography (HPLC). Among four flavonoids, catechin concentration was the highest in all spices and nuts and ranged between 97.1 and 1745.4 µg g-1. Quercetin concentration was the greatest in cinnamon, followed by garlic and cumin and ranged from 0.4 to 65 µg g-1 in other spices and nuts. Lutein concentration ranged from 0.1 to 102.8 µg g-1. Of the spices and nuts studied, β-carotene concentration was highest in coriander leaves (74.7 µg g-1), followed by red pepper (12.5 µg g-1) and curry leaves (8.5 µg g-1). This research shows that consumption of south Indian spices and nuts could substantially benefit consumers living in regions experiencing Vitamin A and other micronutrient deficiencies.


TP53 codon 72 Arg/Arg polymorphism is associated with a higher risk for inflammatory bowel disease development.
To investigate the association between tumor protein 53 (TP53) codon 72 polymorphisms and the risk for inflammatory bowel disease (IBD) development. Numerous genetic and epigenetic drivers have been identified for IBD including the TP53 gene. Pathogenic mutations in TP53 gene have only been reported in 50% of colorectal cancer (CRC) patients. A single nucleotide polymorphism (SNP) in the TP53 gene resulting in the presence of either arginine (Arg) or proline (Pro) or both at codon 72 was shown to alter TP53 tumor-suppressor properties. This SNP has been investigated as a risk factor for numerous cancers, including CRC. In this study we analyzed TP53 codon 72 polymorphism distribution in 461 IBD, 181 primary sclerosing cholangitis patients and 62 healthy controls. Genotyping of TP53 was performed by sequencing and restriction fragment length polymorphism analysis of genomic DNA extracted from peripheral blood. The most frequent TP53 genotype in IBD patients was Arg/Arg occurring in 54%-64% of cases (and in only 32% of controls). Arg/Pro was the most prevalent genotype in controls (53%) and less common in patients (31%-40%). Pro/Pro frequency was not significantly different between controls and IBD patients. The data suggests that the TP53 codon 72 Arg/Arg genotype is associated with increased risk for IBD development.


[Charcoal and isoflurane alveolar washout in low-flow circuit].
The inclusion of charcoal filters in anaesthetic low-flow systems contributes to the acceleration of the kinetics of isoflurane (Forane). In twenty subjects, scheduled for extra- and intracranial surgery, ventilated with a low-flow system (Ohmeda Excel OAV7750 with rebreathing cassette) with a mean total flow of 0.7 l/min, awakening was complete within 5 minutes from stopping isoflurane and including charcoal in the circuit. At the awakening, the expiratory concentration of isoflurane was 0.23% (95% confidence intervals: 0.19-0.27%): these values are similar to those of MACawake of isoflurane after fast alveolar washout. The use of charcoal during low-flow anaesthesia makes low-flow systems more flexible in their use; the anaesthetic level is more easily controllable and accidental overdosing of volatile anaesthetics can be immediately removed.


Endoscopic evacuation of septated chronic subdural hemorrhage - Technical considerations, results, and outcome.
Chronic subdural hematoma (cSDH) is a common entity in the elderly. Homogeneous or well-liquefied CSDH has a standard line of treatment through burr hole and irrigation. However, the management of septated chronic subdural hematoma (sCSDH) with multiple membranes does not have a well-defined surgical approach. The neomembranes forming septations prevent evacuation of clots through burr holes, and the small remaining loculi with clots will enlarge overtime to cause recurrence. Patients with sCSDH were operated through a minicraniotomy (2.5 cm × 2.5 cm) using rigid endoscopes for visualization of the subdural space. Using endoscope, the entire subdural space can be visualized. The neomembranes are removed with standard neurosurgical microinstruments. The entire cavity is irrigated under vision to remove all clots and ensures hemostasis. Eighty-three endoscope-assisted evacuations were done in 68 patients from January 2016 to April 2020. Fifty (73.5%) patients had unilateral and 18 (26.5%) had bilateral subdural. Only 1 patient (1.47%) had a clinically significant recollection of subdural bleeding 1 month after the procedure. Over a mean follow-up period of 25.3 months (range 1-53 months), rest of patients did not show any recollection. Endoscopic evacuation of sCSDH is a safe and effective method and can be used to improve clot evacuation, and remove neomembranes under direct vision to reduce the rates of recollection. This method also obviates the need for larger craniotomies to remove membranes.


Tc-99m HIDA dosimetry in patients with various hepatic disorders.
The pharmacodynamics of Tc-99m dimethyliminodiacetic acid were studied for normal subjects and for patients with a variety of hepatobiliary disorders. It was determined that, in normal subjects, approximately 65% of the gallbladder agent bypassed the gallbladder and was excreted directly from the liver into the small intestine. This bypassing of the gallbladder was even higher in patients with cystic-duct or common-duct obstruction. The radiation burdens to the gallbladder wall and other critical organs were calculated using the dynamic data obtained from patients with a variety of gallbladder disease. The dose to the gallbladder wall was found to be significantly lower than previously reported. Gallbladder ejection and clearance characteristics when stimulated by food intake were studied for normal subjects. Dosimetry calculations demonstrated a fivefold reduction of absorbed dose to the gallbladder wall when the gallbladder was stimulated to contract using a fatty meal. Accordingly, a fatty meal is recommended for patients at the end of all gallbladder imaging studies.


[SUCCESSFUL INGUINAL ORCHIECTOMY IN A PATIENT WITH A PAINFUL METASTATIC SPERMATIC CORD TUMOR: A CASE REPORT].
A 71-year-old man was referred to our department due to inflammation in the right scrotum. A tumor in the right spermatic cord was suspected on palpation, and abdominal computed tomography revealed a 4-cm mass in the tail of the pancreas and a low-density lesion in the liver segment 6. In addition, the patient's serum level of CA19-9 was high, at 135.7 U/mi. We referred the patient to our institution's Department of Gastroenterology, where he was diagnosed as having a liver metastasis from pancreatic cancer. Despite three courses of gemcitabine and erlotinib combination therapy for pancreatic cancer, his serum level of CA19-9 increased to 744.0 U/m, indicating no response to chemotherapy. Because uncontrollable pain developed in the right scrotum and right inguinal area during the course of treatment, inguinal orchiectomy was performed for pain management and pathological diagnosis. Careful examination revealed a hard, whitish tumor occupying the right spermatic cord and extending from the epididymis to the internal inguinal ring. Because a palpable mass in the peritoneum near the internal inguinal ring was detected, part of the peritoneum was resected concurrently. Pathological findings were remarkable with spermatic cord metastasis and peritoneal dissemination from pancreatic cancer. Pain subsided postoperatively and no analgesics were needed. Pancreatic cancer accompanied by spermatic cord metastasis and peritoneal dissemination is extremely rare. Surgical resection in the present case provided effective treatment of the intractable pain due to spermatic cord metastasis. To the best of our knowledge, this is only the 14th case reported in Japan of spermatic cord metastasis from pancreatic cancer as a primary cancer.


Movement-induced uncoupling of primary sensory and motor areas in focal task-specific hand dystonia.
Due to growing evidence of sensorimotor integration impairment in focal task-specific hand dystonia, we aimed at describing primary sensory (S1) and primary motor (M1) cortex source activities and their functional cross-talk during a non-dystonia-inducing sensorimotor task free of biases generated by the interfering with the occurrence of dystonic movements. Magnetoencephalographic brain signals and opponens pollicis (OP) electromyographic activities were acquired at rest and during a simple isometric contraction performed either alone or in combination with median nerve stimulation. The task was performed separately with the right and left hand by eight patients suffering from focal task-specific hand dystonia and by eight healthy volunteers. Through an ad hoc procedure Functional Source Separation (FSS), distinct sources were identified in S1 (FSS1) and M1 (FSM1) devoted to hand control. Spectral properties and functional coupling (coherence) between the two sources were assessed in alpha [8,13]Hz, beta [14,32]Hz and gamma [33,45]Hz frequency bands. No differences were found between spectral properties of patients and controls for either FSM1 or FSS1 cerebral sources. Functional coupling between FSM1 and FSS1 (gamma band coherence), while comparable between dystonic patients and healthy controls at rest, was selectively reduced in patients during movement. All findings were present in both hemispheres. Because previous literature has shown that gamma-band sensory-motor synchronization reflects an efficiency index of sensory-motor integration, our data demonstrate that, in dystonic patients, uncoupling replaces the functional coupling required for efficient sensory-motor control during motor exertion. The presence of bi-hemispheric abnormalities in unilateral hand dystonia supports the presence of an endophenotypic trait.


Understanding Pulmonary Stress-Strain Relationships in Severe ARDS and Its Implications for Designing a Safer Approach to Setting the Ventilator.
This review describes the current understanding of the lungs' response to deforming stress under conditions of both normal physiology and acute lung injury. Several limiting assumptions are needed to infer lung parenchymal stress and strain from airway pressure, volume, and flow data from mechanically ventilated patients with injured lungs. These assumptions include the effects of the chest wall on lung-surface pressure, its topographical distribution, and the effects of non-uniform tissue properties on local parenchymal stresses. In addition, there is a spectrum of biophysical lung injury mechanisms that involves normal as well as tangential alveolar wall stresses. To these are added important secondary effects on pulmonary vascular resistance and right heart function. Understanding both the assumptions of lung mechanics and the scope of injury mechanisms operating during ARDS is necessary to interpret the results of clinical trials that inform prevailing ventilator-management guidelines. The implications issuing from these 3 topics inform a safer approach to setting and adjusting the ventilator to minimize the risk of ventilator-induced lung injury. This is enumerated in a 5-step approach that can be used to guide ventilator management of unstable patients with severe lung injury.


Papilledema: epidemiology, etiology, and clinical management.
Papilledema is optic disc swelling due to high intracranial pressure. Possible conditions causing high intracranial pressure and papilledema include intracerebral mass lesions, cerebral hemorrhage, head trauma, meningitis, hydrocephalus, spinal cord lesions, impairment of cerebral sinus drainage, anomalies of the cranium, and idiopathic intracranial hypertension (IIH). Irrespective of the cause, visual loss is the feared morbidity of papilledema, and the main mechanism of optic nerve damage is intraneuronal ischemia secondary to axoplasmic flow stasis. Treatment is directed at correcting the underlying cause. In cases where there is no other identifiable cause for intracranial hypertension (ie, IIH) the available options include both medical and surgical modalities. Weight loss and diuretics remain the mainstays for treatment of IIH, and surgery is typically reserved for patients who fail, are intolerant to, or non-compliant with maximum medical therapy.


In vitro activity of ferroquine (SAR97193) is independent of chloroquine resistance in Plasmodium falciparum.
Nowadays, chloroquine-resistant malaria appears in almost all endemic regions. Ferroquine is a derivative of chloroquine and shows good activity in vitro and in animal models, but the development of cross-resistance is of concern. We tested in vitro susceptibilities of Plasmodium falciparum field isolates from Gabon to ferroquine, chloroquine, and artesunate. As expected, chloroquine resistance was present in all parasite isolates (median 50% inhibitory concentration = 113 nmol/L). Ferroquine (1.94 nmol/L) and artesunate (0.96 nmol/L) were highly active, and no significant correlation between any of the three drugs was observed. In contrast to our findings, previous studies showed an association between chloroquine and ferroquine activities. We could reproduce this association by using different initial parasitemias, but analysis of covariance revealed that initial parasitemia and not parasite strain was the critical determinant for the correlation between chloroquine and ferroquine activities. We conclude that ferroquine is highly active in chloroquine-resistant parasites, and we anticipate no enhanced selection for resistance against ferroquine in chloroquine-resistant parasites.


Cyanogenesis and the role of cyanogenic compounds in insects.
The cyanogenic system comprising cyanogenic glycosides, hydroxynitriles (cyanohydrins), beta-glucosidases and nitrile lyases is widespread in the plant kingdom but also occurs in several arthropods. A few insects were found to contain mandelonitrile and, in one case, a small amount of prunasin was detected. Cardiospermin and gynocardin occur in one insect, and the cyanoglucosides linamarin and lotaustralin are found in several species of the lepidopterans. Biosynthesis of these cyanoglucosides has been studied in two of these species and their sequestration has been investigated in one species. For Zygaena trifolii the presence of the entire cyanide-handling system indicates an important function of these compounds. So far, their function as defensive compounds seems likely on the basis of their ability to generate HCN and their localization, and appears to be indicated by some feeding experiments with potential predators.


Sago supplementation for recovery from cycling in a warm-humid environment and its influence on subsequent cycling physiology and performance.
This study determined whether sago porridge ingested immediately after exercise (Exercise 1) in warm-humid conditions (30 ± 1°C, 71 ± 4 % RH; 20 km·h-1 frontal airflow) conferred more rapid recovery, as measured by repeat performance (Exercise 2), compared to a control condition. Eight well-trained, male cyclists/triathletes (34 ± 9 y, VO2peak 70 ± 10 ml·kg-1·min-1, peak aerobic power 413 ± 75 W) completed two 15-min time-trials pre-loaded with 15-min warm-up cycling following >24h standardization of training and diet. Mean power output was not different between trials during Exercise 1 (286 ± 67 vs. 281 ± 59 W), however, was reduced during Exercise 2 for control (274 ± 61 W) but not sago (283 ± 60 W) that led to a significant performance decrement (vs. Exercise 1) of 3.9% for control and an improvement (vs. control) of 3.7% for sago during Exercise 2 (P < 0.05). Sago ingestion was also associated with higher blood glucose concentrations during recovery compared to control. These results indicate that feeding sago during recovery from exercise in a warm-humid environment improves recovery of performance during a subsequent exercise bout when compared to a water-only control. As these effects were larger than the test-retest coefficient of variation for work completed during the 15-min time-trial (2.3%) it can be confidently concluded that the observed effects are real.


Influence of polydispersity on the phase behavior of colloidal goethite.
The effect of fractionation on the phase behavior of colloidal goethite dispersions with different polydispersities (17%, 35%, and 55% in length) has been studied by small angle x-ray scattering and transmission electron microscopy. All systems show at least nematic and smectic phases. The occurrence of the latter phase at such a high polydispersity is remarkable. It is shown that in the highly polydisperse systems strong fractionation occurs, which is able to reduce the local length polydispersity up to a factor of 2. A columnar phase was only found in the 35% and 55% polydisperse systems. It seems that the columnar phase accommodates the particles that do not fit into the smectic layers and, thus, reduces the length polydispersity within the smectic phase even further. The fact that a columnar phase was not found in the system of lowest polydispersity indicates that the smectic phase is the most stable phase at higher concentrations.


Expression of basal lamina protein mRNAs in the early embryonic chick eye.
Laminin, collagen IV, collagen XVIII, agrin, and nidogen are major protein constituents of the chick retinal basal lamina. To determine their sites of synthesis during de novo basal lamina assembly in vivo, we localized their mRNA expression in the eye during maximum expansion of the retina between embryonic day (E) 2.5 and E6. Our in situ hybridization studies showed that the expression pattern of every basal lamina protein mRNA in the developing eye is unique. Collagen IV and perlecan originate predominantly from the lens epithelium, whereas collagen XVIII, nidogen, and the laminin gamma 1 and beta1 chains are synthesized mainly by the ciliary body. Agrin, collagen XVIII, collagen IV, and laminin gamma 1 also originate from cells of the optic disc. The only basal lamina protein that is synthesized by the neural retina throughout development is agrin with ganglion cells as its main source. Some of the mRNAs have short, transient expressions in the retina, most notably that of collagen IV and laminin gamma 1, both of which appear in the ventral retina between E4 and E5. That most retinal basal lamina proteins originate from extraretinal tissues infers that the basal lamina proteins have to be shed from the lens, optic disc, and ciliary body into the vitreous body. The assembly of the retinal basal lamina then occurs by the binding of these proteins by cellular receptor proteins on the vitreal endfeet of the retinal neuroepithelial cells.


Warthin's tumor--epithelial cell differences.
An immunohistochemical technic to localize IgA and a histochemical technic to demonstrate beta-D-galactose and N-acetyl-S-galactosamine by peanut agglutinin are applied to paraffin-embedded sections of Warthin's tumor. The luminal layer of epithelium is positive for IgA, while the basal layer is positive for peanut agglutinin. The luminal layer epithelium apparently serves as the route through which IgA (derived from plasma cells in the lymphoid stroma) is secreted into the cystic spaces. The apical cytoplasmic staining for peanut agglutinin in the basal layer is uniquely different from the peanut agglutinin staining pattern in the normal parotid gland. We conclude that the two-layer epithelium of Warthin's tumor is different in morphology, biochemistry, and function.


[The making of hygienic modernity in Meiji Japan, 1868-1905].
This article is based on conceptual and methodological understanding of hygienic modernity in the nineteenth-century Western countries: one is the concept of modern hygiene in the context of modern state and the other is methodological relation of modern hygiene to scientific theory of germ . While modern state calls for the institutionalization of medical police as an administrative tool for consolidating the governmentality what Michel Foucault calls, scientific 'invention' of germ may be considered as 'logical, philosophical and historiographical'. Furthermore, the Meiji medicine men preferred Koch's to Pasteur's laboratory framework, not because the former was scientific than the latter but because Koch's programs were more compatible with imperial needs. The objective of this paper is to investigate four ways in which hygienic modernity had been established in Meiji Japan; (i) how Meiji imperialists perceived and managed to control Japanese hygienic condition, (ii) how Meiji-leading doctors learned about the German modern system of hygiene to consolidate Meiji empire; (iii) how modern germ theory functioned as the formation of imperial bodies in Meiji period; and (iv) how modem military hygiene contributed to Japanese defeat of Russia. Although I try to contend that modern hygiene was adopted as one of the most significant strategies for intensifying and extending the Meiji empire, this paper has some limits in not identifying how Japanese perception of infectious diseases were culturally adaptive to science-based hygienic programs the Meiji administrators had installed.


Reporting of Surgically Removed Lymph Nodes for Breast Tumors: Recommendations From the International Collaboration on Cancer Reporting.
The International Collaboration on Cancer Reporting (ICCR), supported by major pathology and cancer organizations, aims at the standardization of evidence-based pathology reporting of different types of cancers, with the inclusion of all parameters deemed to be relevant for best patient care and future data collection. Lymph node metastasis is one of the most important prognostic factors in breast cancer. To produce a histopathology reporting guide by a panel of recognized experts from the fields of pathology and surgery with elements deemed to be core (required) and noncore (recommended) to report when assessing regional lymph nodes of patients with breast cancer. Published literature, previous guidelines/recommendations, and current cancer staging principles were the basis of the data set drafted by the expert panel. This was discussed in a series of teleconferences and email communications. The draft data set was then made available for public consultation through the ICCR Web site. After this consultation and ICCR ratification, the data set was finalized. The ICCR has published a data set for the reporting of surgically removed lymph nodes (including sentinel lymph node biopsy, axillary lymph node dissection, targeted axillary surgery, and lymph node sampling specimens) for breast tumors. This is part of a series of 4 ICCR breast cancer-related data sets. It includes 10 core elements along with 2 noncore elements. This should allow for synoptic reporting, which is more precise, uniform, and complete than nonsynoptic reporting, and leads to improved patient outcomes.


Chronobiology in hematology and immunology.
The hematopoietic and the immune systems in all their components are characterized by a multifrequency time structure with prominent rhythms in cell proliferation and cell function in the circadian, infradian, and rhythms in cell proliferation and cell function in the circadian, infradian, and circannual frequency ranges. The circulating formed elements in the peripheral blood show highly reproducible circadian rhythms. The timing and the extent of these rhythms were established in a clinically healthy human population and are shown as chronograms, cosinor summaries and, for some high-amplitude rhythms, as time-qualified reference ranges (chronodesms). Not only the number but also the reactivity of circulating blood cells varies predictably as a function of time as shown for the circadian rhythm in responsiveness of human and murine lymphocytes in vitro to lectin mitogens (phytohemagglutinin and pokeweed mitogen). Some circadian rhythms of hematologic functions appear to be innate and are presumably genetically determined but are modulated and adjusted in their timing by environmental factors, so-called synchronizers. Phase alterations in the circadian rhythms of hematologic parameters of human subjects and of mice by manipulation of the activity-rest or light-dark schedule and/or of the time of food uptake are presented. Characteristically these functions do not change their timing immediately after a shift in synchronizer phase but adapt over several and in some instances over many transient cycles. The circadian rhythm of cell proliferation in the mammalian bone marrow and lymphoid system as shown in mice in vivo and in vitro may lend itself to timed treatment with cell-cycle-specific and nonspecific agents in an attempt to maximize the desired and to minimize the undesired treatment effects upon the marrow. Differences in response, and susceptibility of cells and tissues at different stages of their circadian and circaseptan (about 7-day) rhythms and presumably of cyclic variations in other frequencies are expected to lead to the development of a chronopharmacology of the hematopoietic and immune system. Infradian rhythms of several frequencies have been described for numerous hematologic and immune functions. Some of these, i.e., in the circaseptan frequency range, seem to be of importance for humoral and for cell mediated immune functions including allograft rejection. Infradian rhythms with periods of 19 to 22 days seem to occur in some hematologic functions and are very prominent in cyclic neutropenia and (with shorter periods) in its animal model, the grey collie syndrome.(ABSTRACT TRUNCATED AT 400 WORDS)


The Hazards of Regeneration: From Morgan's Legacy to Evo-Devo.
In his prominent book Regeneration (1901), T.H. Morgan's collected and synthesized theoretical and experimental findings from a diverse array of regenerating animals and plants. Through his endeavor, he introduced a new way to study regeneration and its evolution, setting a conceptual framework that still guides today's research and that embraces the contemporary evolutionary and developmental approaches.In the first part of the chapter, we summarize Morgan's major tenets and use it as a narrative thread to advocate interpreting regenerative biology through the theoretical tools provided by evolution and developmental biology, but also to highlight potential caveats resulting from the rapid proliferation of comparative studies and from the expansion of experimental laboratory models. In the second part, we review some experimental evo-devo approaches, highlighting their power and some of their interpretative dangers. Finally, in order to further understand the evolution of regenerative abilities, we portray an adaptive perspective on the evolution of regeneration and suggest a framework for investigating the adaptive nature of regeneration.


Development of Peptidomimetic Inhibitors of the ERG Gene Fusion Product in Prostate Cancer.
Transcription factors play a key role in the development of diverse cancers, and therapeutically targeting them has remained a challenge. In prostate cancer, the gene encoding the transcription factor ERG is recurrently rearranged and plays a critical role in prostate oncogenesis. Here, we identified a series of peptides that interact specifically with the DNA binding domain of ERG. ERG inhibitory peptides (EIPs) and derived peptidomimetics bound ERG with high affinity and specificity, leading to proteolytic degradation of the ERG protein. The EIPs attenuated ERG-mediated transcription, chromatin recruitment, protein-protein interactions, cell invasion and proliferation, and tumor growth. Thus, peptidomimetic targeting of transcription factor fusion products may provide a promising therapeutic strategy for prostate cancer as well as other malignancies.


Licensing age issues: deliberations from a workshop devoted to this topic.
To highlight the issues and discuss the research evidence regarding safety, mobility, and other consequences of different licensing ages. Information included is based on presentations and discussions at a 1-day workshop on licensing age issues and a review and synthesis of the international literature. The literature indicates that higher licensing ages are associated with safety benefits. There is an associated mobility loss, more likely to be an issue in rural states. Legislative attempts to raise the minimum age for independent driving in the United States--for example, from 16 to 17--have been resisted, although in some states the age has been raised indirectly through graduated driver licensing (GDL) policies. Jurisdictions can achieve reductions in teenage crashes by raising the licensing age. This can be done directly or indirectly by strengthening GDL systems, in particular extending the minimum length of the learner period. Supplementary materials are available for this article. Go to the publisher's online edition of Traffic Injury Prevention for the following supplemental resource: List of workshop participants.


Aziridine carboxylate from D-glucose: synthesis of polyhydroxylated piperidine, pyrrolidine alkaloids and study of their glycosidase inhibition.
The D-glucose derived aziridine carboxylate 5 was obtained from (E)-ethyl-6-bromo-1,2-O-isopropylidene-3-O-benzyl-5-deoxy-alpha-D-xylo-5-eno-heptofuranuronate 4 through conjugate addition of benzylamine and in situ intramolecular nucleophilic expulsion of bromine. The regioselective aziridine ring-opening, using water as a nucleophile, resulted in the alpha-hydroxy-beta-aminoester 6, which was exploited in the synthesis of six and five membered azasugars 1b/1c and 2b/2c, respectively. The glycosidase inhibitory activity of the title compounds was evaluated.


Is Recovery from Cannabis Dependence Possible? Factors that Help or Hinder Recovery in a National Sample of Canadians with a History of Cannabis Dependence.
To identify among Canadian adults who have ever been dependent upon cannabis, the prevalence of risk and protective factors associated with (1) cannabis remission, (2) the absence of psychiatric disorders or addictions in the past year (APD), and (3) positive mental health (PMH). Data from Statistics Canada's nationally representative 2012 Canadian Community Health Survey-Mental Health (n = 20, 777, of whom 336 have a history of cannabis dependence) was used. Chi-square tests and logistic regression analyses were conducted. The World Health Organization Composite International Diagnostic Interview (WHO-CIDI) measures were used to determine lifetime cannabis dependence, past-year remission from cannabis depression, and the absence of psychiatric disorders in the past year (APD) (i.e., no suicidal ideation, depressive episodes, anxiety disorders, bipolar disorders, or any substance dependence). PMH is comprised of three factors: APD, happiness or life satisfaction and social and psychological well-being. Among those with a history of cannabis dependence, 72% were in remission from cannabis dependence. Although 53% were free of major psychiatric disorders and any substance dependence and 43% of respondents were in PMH, these percentages were dramatically lower than those without a history of cannabis dependence (92% and 74%, respectively). Positive outcomes were more common among women, older respondents, those with higher levels of social support, and those who had never had major depressive disorder or generalized anxiety disorder. Although many Canadians with a history of cannabis dependence achieve remission and a large minority are truly resilient and achieve PMH, many are failing to thrive. Targeted outreach is warranted for the most vulnerable individuals with a history of cannabis dependence (e.g., men, younger respondents, those with low social support and a history of mental illness).