Technical note: Towards more realistic 4DCT(MRI) numerical lung phantoms.
Numerical 4D phantoms, together with associated ground truth motion, offer a flexible and comprehensive data set for realistic simulations in radiotherapy and radiology in target sites affected by respiratory motion. We present an openly available upgrade to previously reported methods for generating realistic 4DCT lung numerical phantoms, which now incorporate respiratory ribcage motion and improved lung density representation throughout the breathing cycle. Density information of reference CTs, toget her with motion from multiple breathing cycle 4DMRIs have been combined to generate synthetic 4DCTs (4DCT(MRI)s). Inter-subject correspondence between the CT and MRI anatomy was first established via deformable image registration (DIR) of binary masks of the lungs and ribcage. Ribcage and lung motions were extracted independently from the 4DMRIs using DIR and applied to the corresponding locations in the CT after post-processing to preserve sliding organ motion. In addition, based on the Jacobian determinant of the resulting deformation vector fields, lung densities were scaled on a voxel-wise basis to more accurately represent changes in local lung density. For validating this process, synthetic 4DCTs, referred to as 4DCT(CT)s, were compared to the originating 4DCTs using motion extracted from the latter, and the dosimetric impact of the new features of ribcage motion and density correction were analyzed using pencil beam scanned proton 4D dose calculations. Lung density scaling led to a reduction of maximum mean lung Hounsfield units (HU) differences from 45 to 12 HU when comparing simulated 4DCT(CT)s to their originating 4DCTs. Comparing 4D dose distributions calculated on the enhanced 4DCT(CT)s to those on the original 4DCTs yielded 2%/2 mm gamma pass rates above 97% with an average improvement of 1.4% compared to previously reported phantoms. A previously reported 4DCT(MRI) workflow has been successfully improved and the resulting numerical phantoms exhibit more accurate lung density representations and realistic ribcage motion.


Genotypic spectrum and phenotype correlations of ABCA4-associated disease in patients of south Asian descent.
Variants in the ABCA4 gene are the most common cause of juvenile-onset blindness affecting close to 1 in 10 000 people worldwide. Disease severity varies largely according to genotype, which can be specific to ethnic and racial groups. Here we investigate the spectrum of ABCA4 variation and its phenotypic expression in 38 patients of South Asian descent, notably from India, Pakistan, Bangladesh and Sri Lanka. Sequencing of all exons and flanking intronic sequences of ABCA4 revealed disease-causing variants in all patients: 3 in 2.6%, 2 in 81.6% and 1 in 15.8%. Altogether, 36 distinct variants were identified, including 9 previously not described. The most frequent variant c.5882G>A, p.(G1961E) was found in half the patients, the highest ever reported in a single study cohort. The South Asian founder variant c.859-9T>C was identified along with other founder variants ascribed to Danish, Chinese, Mexican and African patients. Patients carrying c.5882G>A, p.(G1961E) exhibited a consistently confined disease phenotype, normal quantitative autofluorescence (qAF) levels and preserved full-field ERG (ffERG) while c.859-9T>C resulted in widespread disease, significantly elevated qAF and reduced to non-detectable ffERG. South Asian patients present with a relatively unique ABCA4 profile comprised of various ethnic founder variants resulting in two or three major retinal phenotypes.


Alkaline-Earth-Catalyzed Dehydrocoupling of Amines and Boranes.
Dehydrocoupling reactions between the boranes HBpin and 9-borabicyclo[3.3.1]nonane and a range of amines and anilines ensue under very mild reaction conditions in the presence of a simple β-diketiminato magnesium n-butyl precatalyst. The facility of the reactions is suggested to be a function of the Lewis acidity of the borane substrate, and is dictated by resultant pre-equilibria between, and the relative stability of, magnesium hydride and borohydride intermediates during the course of the catalysis.


Effect of bile acids on formation of the mutagen, quercetin, from two flavonol glycoside precursors by human gut bacterial preparations.
Human fecal cultures, induced with either of the flavonols, quercitrin or rutin, were grown in the presence of various concentrations of chenodeoxycholic acid, deoxycholic acid or cholic acid. Cell-free preparations (fecal preparations) from these cultures were then incubated with rutin or quercitrin. The formation of the aglycone, quercetin, was monitored by the Ames assay using tester strain TA98. The presence of chenodeoxycholic or deoxycholic acids in the quercitrin-induced culture resulted in a fecal preparation which enhanced the mutagenesis of quercitrin approximately two-fold at optimal concentrations of 0.6 mM and 0.8 mM respectively. Higher concentrations of these bile acids decreased the activity of the fecal preparations. Cholic acid gave similar results except a much higher concentration (3.0 mM) was required to achieve this effect. Analogous results with rutin-induced cultures were less clear cut: considerable variation in bile acid effect was noted among volunteers. The authors propose that bile acid in the medium may enhance the ability of rutin- and quercitrin-glycosidase elaborating organisms to successfully compete with other microbial populations. Additionally, the greater variation in results using rutin as inducer may reflect more heterogeneous populations of organisms active against this substrate. The possible role of bile acids and flavonols in bowel cancer is discussed.


Fabrication of magnetic hydroxypropyl cellulose-g-poly(acrylic acid) porous spheres via Pickering high internal phase emulsion for removal of Cu(2+) and Cd(2.).
A series of magnetic hydroxypropyl cellulose-g-poly(acrylic acid) porous spheres were prepared via O/W Pickering high internal phase emulsions (HIPEs) integrated precipitation polymerization. The structure and composition of modified Fe3O4 and porous structures were characterized by TEM, XRD, TGA and SEM. The results indicated that the silanized Fe3O4 can influence greatly the pore structure of magnetic porous sphere in addition to non-negligible impacts of the proportion of mixed solvent and co-surfactant. The adsorption experiment demonstrated that the adsorption equilibrium can be reached within 40min and the maximal adsorption capacity was 300.00mg/g for Cd(2+) and 242.72mg/g for Cu(2+), suggesting its fast adsorption kinetics and high adsorption capacity. After five adsorption-desorption cycles, no significant changes in the adsorption capacity were observed, suggesting its excellent reusability. The magnetic porous sphere can be easily separated from the solution and then find its potential as a recyclable material for highly efficient removal of heavy metals.


On the differences between two-dimensional and three-dimensional simulations for assessing elastographic image quality: a simulation study.
In this work, we introduced an elastographic simulation framework, which estimates upper bounds on elastographic image quality by accounting for three-dimensional (3D) tissue motion and the 3D nature of the ultrasound beam. For the boundary conditions and the range of applied strains considered in this study, it was observed that for applied strains smaller than 0.7%, fast two-dimensional (2D) simulations and 3D simulations predicted similar upper bounds on elastographic signal-to-noise (SNR(e)) and contrast-to-noise ratios (CNR(e)); however, for applied strains greater than 0.7%, the predictions by 2D simulations grossly overestimated the achievable results when compared with upper bound results from 3D simulations. It was also found that linear increments in the elevational-to-lateral beamwidth ratio (beam ratio) resulted in nonlinear degradation in the achievable upper bounds on elastographic signal-to-noise ratio. For the modulus contrast ratio of ten between the target and the background, the peak difference in the prediction of contrast-to-noise by 2D and 3D simulations was approximately 10 dB, whereas, for modulus contrast ratio of 1.5, the peak difference increased to approximately 30 dB. No significant difference was observed between the spatial resolution predicted by 2D and 3D simulations; however, increase in beam ratio resulted in decrease in target detectability, especially at lower modulus contrast ratios.


The effects of excitotoxic lesions of the substantia innominata, ventral and dorsal globus pallidus on the acquisition and retention of a conditional visual discrimination: implications for cholinergic hypotheses of learning and memory.
The effects of ibotenic acid-induced lesions of the ventral pallidum/substantia innominata region, the dorsal pallidum or both on the acquisition and retention of a conditional visual discrimination have been studied in the rat. Lesions of the ventral pallidum and large lesions of the dorsal and ventral pallidum severely impaired both the acquisition and retention of the conditional discrimination. Dorsal pallidal lesions had similar, but less marked effects. The same lesions also impaired the retention of a passive avoidance task, but had no effect on a conditioned taste aversion. Neurobiological investigations revealed that the lesions destroyed cholinergic neurons in the magnocellular nucleus basalis and caused reductions in cortical choline acetyltransferase activity of about 30-40%. Tract-tracing experiments indicated that the lesions destroyed, in particular, cholinergic neurons projecting to the frontal dorsolateral cortex and also those projecting to more posterior cortex, but not the occipital lobes. Contingency analysis of the behavioural, neurochemical and neuroanatomical data indicated that those animals with the largest decreases in choline acetyltransferase activity, or the largest areas of neuronal loss in the ventral and dorsal globus pallidus, were most impaired in the retention of the conditional discrimination. The results do not, therefore, indicate a simple relationship between cholinergic neuronal loss and the retention of response rules essential for performance of the task ("reference memory"). The relevance of the results to cholinergic hypotheses of learning and memory is discussed.


The impact of lockdown on nitrogen dioxide (NO2) over Central Asian countries during the COVID-19 pandemic.
Nitrogen dioxide (NO2) is one of the main air pollutants, formed due to both natural and anthropogenic processes, which has a significant negative impact on human health. The COVID-19 pandemic has prompted countries to take various measures, including social distancing or stay-at-home orders. This study analyzes the impact of COVID-19 lockdown measures on nitrogen dioxide (NO2) changes in Central Asian countries. Data from TROPOspheric Monitoring Instrument (TROPOMI) on the Sentinel-5 Precursor satellite, as well as meteorological data, make it possible to assess changes in NO2 concentration in countries and major cities in the region. In particular, the obtained satellite data show a decreased tropospheric column of NO2. Its decrease during the lockdown (March 19-April 14) ranged from - 5.1% (Tajikistan) to - 11.6% (Turkmenistan). Based on the obtained results, it can be concluded that limitations in anthropogenic activities have led to improvements in air quality. The possible influence of meteorology is not assessed in this study, and the implied uncertainties cannot be quantified. In this way, the level of air pollution is expected to decrease as long as partial or complete lockdown continues.


Oxygen Defect-Induced Metastability in Oxide Semiconductors Probed by Gate Pulse Spectroscopy.
We investigate instability mechanisms in amorphous In-Ga-Zn-O transistors based on bias and illumination stress-recovery experiments coupled with analysis using stretched exponentials and inverse Laplace transform to retrieve the distribution of activation energies associated with metastable oxygen defects. Results show that the recovery process after illumination stress is persistently slow by virtue of defect states with a broad range, 0.85 eV to 1.38 eV, suggesting the presence of ionized oxygen vacancies and interstitials. We also rule out charge trapping/detrapping events since this requires a much smaller activation energy ~0.53 eV, and which tends to be much quicker. These arguments are supported by measurements using a novel gate-pulse spectroscopy probing technique that reveals the post-stress ionized oxygen defect profile, including anti-bonding states within the conduction band.


Resuscitation-induced myocardial necrosis. Catecholamines and defibrillation.
Prolonged resuscitation in adults produces a recognizable pattern of myocardial injury characterized by contraction band necrosis, focal hemorrhage, and coagulation necrosis. To rule out the possibility of these changes being due to ischemia and underlying coronary artery disease, autopsies of 26 children admitted to Stanford from 1981 to 1983 were reviewed. Seventeen had attempted resuscitation with catecholamines and defibrillation; the remainder did not. Sections of myocardium were graded by two observers. For controls, brain-dead heart donors otherwise disease-free and essentially untreated with either defibrillation or beta-active catecholamines were used. Defibrillation alone and catecholamines alone each produced equal amounts of destruction, but using these together resulted in a statistically significant increase in tissue destruction. This suggests that the damaging effects of these agents are synergistic, not additive.


The apparent molecular weight of androgen-binding protein (ABP) in the blood of immature rats differs from that of ABP in the epididymis.
When androgen-binding protein (ABP) in unfractionated immature (20-day old) male rat serum was covalently labeled with the site-specific photoaffinity ligand [3H]17 beta-hydroxy-4,6-androstadien-3-one and analyzed on 5.6% polyacrylamide tube gels containing SDS (SDS-PAGE), a protein of Mr 33,700 +/- 1200 was shown to be specifically labeled. Rat epididymal ABP from unfractionated cytosol analyzed under identical conditions exhibited two androgen-specific peaks of radioactivity, Mr 49,900 +/- 600 and Mr 44,100 +/- 800, which correspond to the previously described subunits of ABP. The apparent molecular weight differences between serum and epididymal ABP were further assessed on preparations of serum ABP that had been partially purified by chromatography on Affi-Gel blue (to remove albumin) and on Sephadex G-150 (to remove other proteins). When these preparations of ABP were photolabeled and analyzed by SDS-PAGE as above, two subunits of Mr 61,700 +/- 1300 and Mr 47,100 +/- 700 were resolved. Serum and epididymal ABP were further purified by androgen affinity chromatography. When these preparations were subjected to SDS-PAGE on slab gels containing 10% polyacrylamide and identified by fluorography of photolabeled ABP or by immunochemical localization following electrophoretic transfer to nitrocellulose, differences in the apparent molecular weight of ABP from the two sources persisted. Immunochemical localization studies on ABPs that had been desialylated with neuraminidase indicated that there was an increased mobility of the subunits, as one would anticipate from removal of carbohydrate. Differences in apparent molecular weight of ABPs from the two sources are likely due to differences in glycosylation.


Functional activity patterns in the forebrain of swimming rats: a 5 min 2-deoxyglucose study.
Effects of 5 min of swimming on functional activity patterns in the rat forebrain were examined by high resolution autoradiographic assessment of [14C]2-deoxyglucose ([14C]2-DG) uptake. In autoradiograms made from swimming rats, the isocortex displayed a columnar pattern in which columns of high optical density, oriented perpendicularly to the cortical surface, were separated by columns of low optical density of similar orientation. Increased [14C]2-DG uptake in swimming rats compared to resting rats was also apparent in the lateral septal nucleus, globus pallidus, and endopiriform nucleus. The results demonstrate that 2-DG can be used in short survival uptake experiments to gain insight into neuroanatomical patterns of functional activity.


Substrate effects on mitochondrial function and tissue lipids in low-flow hypoxia of isolated perfused rat hearts.
A possible causal relationship between tissue FFA contents and the depression in mitochondrial oxidative phosphorylation in myocardial ischaemia has been suggested. To test this hypothesis, the effects of different substrates added to the perfusates of hypoxic, low-flow perfused hearts were examined on oxidative phosphorylation catalysed by mitochondria isolated from such tissue. In an additional series of experiments tissue neutral glyceride and FFA levels were analysed and correlated with changes in mitochondrial function. Mitochondria isolated from hearts with a high tissue FFA content exhibited the lowest ADP/O ratios, RCI and QO2 values. On the other hand, mitochondria isolated from hearts with reduced FFA contents, performed significantly better with respect to these parameters of mitochondrial function studied.


Resting Energy Expenditure, Fetal Biometric Parameters by Ultrasound, and Birthweight in Chinese Pregnant Women With Gestational Diabetes Mellitus.
To explore the relationships between resting energy expenditure (REE) according to indirect calorimetry, fetal biometric parameters by ultrasound, and birthweight in gestational diabetes mellitus (GDM). Sixty-five women with GDM and 60 in the control group were enrolled. The REE, birthweight, and fetal biometric parameters according to ultrasound, including biparietal diameter, head circumference, abdominal circumference (AC), and femur length, were measured. The AC at 29 to 32 weeks and 37 to 40 weeks was larger in the GDM than in the control group (P < 0.01), birthweight was higher in the GDM than in the control group (P < 0.01), and women in the GDM group had higher REE than those in the control group at all stages of pregnancy (P < 0.01). In the control group, all fetal biometric parameters were correlated with birthweight at 37 to 40 weeks (r = 0.418, 0.678, 0.741, and 0.635 for biparietal diameter, head circumference, AC, and femur length, respectively, P < 0.05); however, in the GDM group, only AC was correlated with birthweight at 37 to 40 weeks (r = 0.707; P < 0.05). In the GDM group, REE was correlated with birthweight at all three stages of pregnancy (r = 0.369, 0.381, and 0.446 for 21 to 24, 29 to 32, and 37 to 40 weeks, respectively, P < 0.05), and REE was correlated with AC at 37 to 40 weeks (r = 0.431; P < 0.05). REE is correlated with birthweight in women with GDM from the middle to the end of pregnancy. REE by indirect calorimetry might be potential index for medical nutrition therapy in GDM.


Toxicity and bioaccumulation of tributyltin and triphenyltin on oysters and rock shells collected from Taiwan maricuture area.
The present study was undertaken to evaluate the toxicity of tributyltin (TBT) on oysters (Crassostrea gigas) and bioaccumulation of TBT and triphenyltin (TPhT) on oysters and rock shells (Thais clavigera) from mariculture areas of Taiwan. When treated with concentrations of 0.08, 0.40, 2.00, 10.00 and 50.00 microg TBT/L, the 48-, 72-, 96- and 120-h LC50s of oysters were 44.6, 18.4, 17.9 and 14.3 microg TBT/L, respectively. In the bioaccumulation experiments, oysters and rock shells were exposed to various concentrations of organotins, i.e. A: control, B: 0.40 microg TBT/L, C: 0.40 microg TPhT/L, and D: 0.20 microg TBT/L + 0.20 microg TPhT/L. In general, TPhT was faster accumulated than TBT in both oysters and rock shells and oysters had a higher elimination capability than rock shells. Additionally, greater bioaccumulation and elimination rates had been observed in female oysters than males. To rock shells, the bioaccumulation rate of organotins in imposex females was greater than males and females.


In vitro penetration of pesticides through human newborn foreskin.
The in vitro dermal penetration of 14C-labelled parathion, fenvalerate, carbofuran, and lindane through fresh full-thickness human newborn foreskin was determined at 1, 6, 24, and 48 h. The pesticides were applied to a constant dosing area (0.031 cm2), and a fixed dose (1.18 microgram), for each of the compounds studied. 90%, or greater, of the labelled pesticides were recovered in all cases. Carbofuran showed the greatest mean penetration of 82% followed by parathion and lindane with mean penetrations of 79 and 66%, respectively. Fenvalerate exhibited a mean penetration of 9% which is significantly lower than that of the other three compounds. No difference was noted in the penetration of pesticides through human skin from blacks and whites.


An analysis of the changes in the surfaces of metallic femoral components in hip prostheses. A study of 60 prostheses removed after 1-20 years.
A study of 60 femoral prosthetic components removed after 1-20 years allowed us to study the behaviour of the metallic surface in real life conditions. Changes were observed exclusively in cemented prostheses. They consisted of corrosion phenomena characteristic of the components of steel EN 58 J and 316 S, and wear phenomena secondary to mobilisation. The latter were observed in steel components as well as in those in Co-Cr alloy. The areas of corrosion in the steel prostheses were characteristically distributed, indicating a combination of causal factors, including an insufficient capacity of passivation of the metal and the particular situation of the cement-to-metal interface.


Modulation of growth cone calcium current is mediated by a PTX-sensitive G protein.
Growth cones of isolated neurons B5 of Helisoma were voltage clamped in the whole-cell configuration. Depolarization of growth cones to -20 mV or greater activated a high-voltage-activated (HVA) calcium current. Addition of the neuropeptide FMRFamide (1 microM), which causes a presynaptic inhibition of synaptic transmission, reversibly reduced the calcium current magnitude. This inhibitory effect is mediated by a pertussis toxin (PTX)-sensitive G protein. Dialysis with the non-hydrolyzable GTP analogs GTP gamma S and Gpp(NH)p caused FMRFamide's effect to become irreversible. Dialysis with GDP beta S or preincubation with PTX prevented FMRFamide from reducing the calcium current. Thus, one role of growth cone G proteins is to modulate ion channels in growth cone membrane which in turn may control growth cone motility.


Evaluation of the pediatric Bonfils fiberscope for elective endotracheal intubation.
Difficult airway management in children is a particular challenge for anesthesiologists and pediatricians. This study was designed to evaluate the performance of the recently developed pediatric versions of the Bonfils fiberscope for elective endotracheal intubation during routine surgical procedures. After approval by the institutional review board and written informed consent, 55 children (age 6 +/- 4 years) scheduled for elective minor surgical procedures were enrolled. Nineteen children received atropine before the intubation attempt, while in the remaining 36 children, no antisialogogue was used. For endotracheal tubes up to 3.5 mm internal diameter, a fiberscope with outer diameter (OD) 2 mm, and for larger endotracheal tubes, a fiberscope OD 3.5 mm was used. Time to intubation and failure rate were obtained. In the 36 children without and the 19 children with atropine pretreatment, the success rate for tracheal intubation on the first attempt was 69%/78% (25/15 patients). 4/3 patients and 2/0 patients were intubated after two and three attempts, respectively, and in 5/1 patients (14%/5%) intubation failed even after three attempts. Time to intubation was median 58/60 s, 25th-75th percentile 35-100/32-110 s, and range 14-377/18-360 s. In both groups, failed intubations were because of the secretions contaminating the optic aperture. High failure rate and increased intubation times suggest that the pediatric Bonfils fiberscope has significant drawbacks when used for intubation of normal pediatric airways.


Substance P release from K+-depolarized rat brain synaptosomes at one-second resolution.
Substance P release from isolated nerve endings (synaptosomes) prepared from rat brain occurred primarily within the first second of continuous K+-depolarization. If the concentrations of K+ or Ca2+ were decreased there was less substance P release, but the time course of release was similar. Thus the rapid release of substance P occurs over a wide range of depolarization conditions.


Effect of lactobacteria fermentation on structure and physicochemical properties of Chinese yam starch (Dioscorea opposita Thunb.).
Biotransformation is an effective technique to modify the structure and physicochemical properties of carbohydrates. In this work, Chinese yam (Dioscorea opposita Thunb.) starch was fermented by lactobacteria. The effect of fermentation time (6, 12, 30, 42 and 72 h) on structure and physicochemical properties of Chinese yam starch were investigated. The microstructure was destroyed after lactobacteria fermentation for 42 and 72 h. The X-ray diffraction pattern of Chinese yam starch indicated a transformed A to A + V crystalline type. → 4)-α-d-glucose-(1 → from backbone and unreduced terminal α-d-glucose-(1 → 4 from branch were identified by NMR spectra, and free glucose was only detected in fermented starch at 72 h. With the extension of fermentation time, the crystallinity and thermal parameters increased within 42 h and thereafter decreased. Mw, Mw/Mn, long chains of DP25-36 and DP ≥ 37, peak viscosity, trough viscosity, finally viscosity and setback presented a reverse trend.


Adolescent drug using groups in Chicago parks.
In a northern Chicago neighborhood, observational and interview data were collected at parks, school lots, and beaches where adolescents congregate to buy, sell, and use nonopiate drugs. These sites were geographically distinct from areas where heroin is regularly distributed. Users at each area generally resided in the immediate neighborhood, were well known to one another, were predominantly male, displayed similar socioeconomic, religious and ethnic backgrounds, and had attended the same grade schools and high schools. These sites were relatively stable during the summer months, although visitors occasionally changed locations in response to police harassment. Attendance fluctuated with weather and time of day. Drug use was generally confined to the daily use of marihuana and weekend use of alcohol and sedative-hypnotics, but availability seemed to determine the type and frequency of drug use to a greater extent than drug perference. This study suggests the potential of a fieldwork model for prevention and intervention activities prior to the onset of more intense and diversified drug use.


Using a physics-informed neural network and fault zone acoustic monitoring to predict lab earthquakes.
Predicting failure in solids has broad applications including earthquake prediction which remains an unattainable goal. However, recent machine learning work shows that laboratory earthquakes can be predicted using micro-failure events and temporal evolution of fault zone elastic properties. Remarkably, these results come from purely data-driven models trained with large datasets. Such data are equivalent to centuries of fault motion rendering application to tectonic faulting unclear. In addition, the underlying physics of such predictions is poorly understood. Here, we address scalability using a novel Physics-Informed Neural Network (PINN). Our model encodes fault physics in the deep learning loss function using time-lapse ultrasonic data. PINN models outperform data-driven models and significantly improve transfer learning for small training datasets and conditions outside those used in training. Our work suggests that PINN offers a promising path for machine learning-based failure prediction and, ultimately for improving our understanding of earthquake physics and prediction.


Variations in preference for topical vehicles among demographic groups.
Patient satisfaction and outcomes can be optimized by identifying preferences for topical vehicles by age, gender, and ethnicity. Our study sought to identify variations in preferences for creams, lotions, and ointments among different age groups, genders, and ethnicities. Each demographic group revealed statistically significant differences in vehicle preference (P < .05).


Stem cells accumulate on a decellularized arterial xenograft in vivo.
Surgical interest in complete arterial revascularization is expanding, but some patients lack suitable conduits for this goal. The field of stem cell biology is rapidly expanding and, together with the concepts of tissue engineering, offers the promise of growing autologous grafts in the laboratory. We aim to develop a model using human arteries as vascular grafts in a murine model and to assess the cellular accumulation on these grafts. Human arterial samples were collected and decellularized using an ionic detergent. These vessel scaffolds were then used as grafts in an in vivo mouse model, and the cellular accumulation on them was examined histologically and by cell culture with assessment of their physiologic properties. Left internal mammary artery branches were fully decellularized and successfully implanted into a murine model. Grafts were repopulated by cells expressing stem cell markers cluster of differentiation 34 and stage-specific embryonic antigen, and subsequently expressed markers of mature endothelial and smooth muscle cells (cluster of differentiation 31, calponin, and myosin heavy chain). The migratory capacity of the cultured cells was significantly higher than that of mouse smooth muscle cells (p < 0.001). We describe the successful use of human arteries in a murine graft model, allowing the study of repopulation. Decellularized grafts are repopulated by cells expressing stem cell markers and subsequently express smooth muscle and endothelial cell markers. This model has the potential to be used for further development of laboratory-grown vascular grafts.


An algorithm to quantify intratumor heterogeneity based on alterations of gene expression profiles.
Intratumor heterogeneity (ITH) is a biomarker of tumor progression, metastasis, and immune evasion. Previous studies evaluated ITH mostly based on DNA alterations. Here, we developed a new algorithm (DEPTH) for quantifying ITH based on mRNA alterations in the tumor. DEPTH scores displayed significant correlations with ITH-associated features (genomic instability, tumor advancement, unfavorable prognosis, immunosuppression, and drug response). Compared to DNA-based ITH scores (EXPANDS, PhyloWGS, MATH, and ABSOLUTE), DEPTH scores had stronger correlations with antitumor immune signatures, cell proliferation, stemness, tumor advancement, survival prognosis, and drug response. Compared to two other mRNA-based ITH scores (tITH and sITH), DEPTH scores showed stronger and more consistent associations with genomic instability, unfavorable tumor phenotypes and clinical features, and drug response. We further validated the reliability and robustness of DEPTH in 50 other datasets. In conclusion, DEPTH may provide new insights into tumor biology and potential clinical implications for cancer prognosis and treatment.


Engineering the metabolism and morphology of the filamentous fungus Trichoderma reesei for efficient L-malic acid production.
L-malic acid (MA) is a vital platform chemical with huge market demand because of its broad industrial applications. A cell factory for MA production was engineered by strengthening the intrinsic pathway without inserting foreign genes into Trichoderma reesei. The native MA transporter gene in the T. reesei genome was characterized (trmae1), and its overexpression significantly improved MA production, which increased from 2 to 56.24 g/L. Native pyruvate carboxylase, malate dehydrogenase, malic enzyme, and glucose transporter were overexpressed further to improve the titer and yield of MA production. Fungal morphology was adapted to produce MA in the fermenter by deleting gul1. A titer of 235.8 g/L MA was produced from the final engineered strain in a 5-L fermenter with a yield of 1.48 mol of MA per mol of glucose and productivity of 1.23 g/L/h. This study provides novel insights for understanding and remodeling the MA synthesis pathway.


Insights into mechanisms governing the passive removal of inorganic contaminants from acid mine drainage using permeable reactive barrier.
The permeable reactive barrier has been deemed as the most prudent and pragmatic way to passively manage and remediate acid mine drainage (AMD). Herein, insights into mechanisms governing the removal of inorganic contaminants from AMD using a permeable reactive barrier (PRB), i.e. pervious concrete, were reported. In particular, the effects of varying dosages, i.e., 6, 10, 30, and 60 g, of cementitious materials comprising CEM I 52.5R with or without fly ash, hydrated lime, and gypsum were evaluated whilst the fate of chemical species was underpinned using the state-of-the-art analytical techniques, along with PHREEQC geochemical modelling. The role of gypsum, a product formed from the interaction of PRB with AMD in heavy metals attenuation was also elucidated. Findings revealed cementitious materials to play an indispensable role in the removal of inorganic contaminants from AMD. Furthermore, alkalinity from used materials increases the pH (i.e. pH ≥ 12.5) of AMD leading to the precipitation of chemical species. Specifically, the efficacy registered the following sequence: Lime ≥ CEM I ≥ 30%FA ≥ Gypsum with ≥99 for Al and Fe except for Gypsum which attained ≥98 while the performance for Zn removal registered the following sequence, 97 ≥ 98 ≥ 88.8 ≥ 45% for CEM I ≥ Lime ≥30%FA ≥ Gypsum, respectively. Chemical species exist as divalent, trivalent, oxyanions, and other complexes in solution as predicted by PHREEQC. Moreover, they were removed as metal hydroxides, oxyhydrosulphates, and gypsum hence corroborating findings from XRD, SEM-EDS, and FTIR results. Mechanisms which were responsible for the removal of chemical species were precipitation, adsorption, co-adsorption, co-precipitation, ion exchange, and complexation. Henceforth, this study explicitly demonstrated mechanisms that underpin the removal of inorganic contaminants from AMD using PRB and findings from this study will be used to develop effective PRB for the management of acid mine drainage and the receiving environment.


Animal Culture: How a New Birdsong Went Viral.
A new white-throated sparrow song has overtaken most of Canada in less than 20 years. The explanation for this remarkably fast spread may lie in the southern migratory grounds, where populations from across Canada converge each winter.


Syphilis.
Inoculation of Treponema pallidum during intimate physical contact is followed by development of a papule that rapidly erodes, yielding the syphilitic chancre. Hematogenous dissemination results in secondary syphilis, a multisystem disease characterized by skin rash, lymph node enlargement, hepatitis, arthritis, and central nervous system involvement. In the absence of treatment, a latent period is reached after which tertiary syphilis may appear in an increasing proportion of patients, depending upon the duration of the follow-up.


Impact of the Delayed Initiation of Adjuvant Chemotherapy in the Outcome of Triple Negative Breast Cancer.
Adjuvant chemotherapy decreases the recurrence risk and improves survival rates; however, it is unclear whether a delayed initiation is associated with adverse outcomes, especially in triple negative breast cancer (TNBC). In this study, we evaluated the influence of the time to start adjuvant chemotherapy (TTC) in the outcomes of TNBC. We retrospectively analyzed 15 years of data from patients with TNBC who received adjuvant chemotherapy at the Instituto Nacional de Enfermedades Neoplasicas (Lima, Peru). TTC was categorized into 4 groups: ≤ 30, 31 to 60, 61 to 90, and ≥ 91 days. We evaluated overall survival (OS) and distant recurrence-free survival (DRFS). Cox proportional hazard models were used to identify prognostic factors. In total, 687 patients were included. The mean age at diagnosis was 49.1 years (SD, 11.8 years), and most (62.6%) patients had pathologic stage T2. The median TTC was 48.1 days (SD, 27.4 days); 189 (27.5%) received chemotherapy ≤ 30 days; 329 (47.9%), between 31 and 60 days; 115 (16.7%), between 61 and 90 days; and 54 (7.9%) in ≥ 90 days. In the multivariate analysis, a TTC between 31 and 60 days (hazard ratio [HR], 1.78; 95% confidence interval [CI], 1.17-2.72), 61 and 90 days (HR, 2.38; 95%CI, 1.43-3.97), and ≥ 91 days (HR, 2.45; 95% CI, 1.32-4.55) was associated with an increased mortality in contrast with a TTC < 30 days. Although a TTC between 31 and 60 days, 61 and 90 days, and ≥ 91 days was associated with an increased risk of DRFS (HR, 1.86; 95% CI, 1.24-2.79; HR, 2.34, 95% CI, 1.42-3.867; and HR, 3.16; 95% CI, 1.78-5.61, respectively). A delaying in TTC ≥ 30 days was associated with poorer outcomes. Our data suggest that several efforts should be conducted to avoid a delayed TTC in patients with TNBC.


Recovery process and prognosis of aphasic patients with left putaminal hemorrhage: relationship between hematoma type and language modalities.
To elucidate the precise recovery process and prognosis of language functions in aphasic patients with left putaminal hemorrhage, we investigated 48 aphasic patients classified into 4 groups according to the location and extent of hematoma. The hematoma extended to the corona radiata in all patients, extracapsular in type I (12 cases), to the anterior limb in type II (10 cases), to the posterior limb in type III (12 cases), and to both limbs in type IV (14 cases). The Standard Language Test for Aphasia was performed at 1 month, 3 months, and 6 months after the attack. The type II, III, and IV patients were divided into 2 groups, with and without ventricular rupture of the hemorrhage. At 3 and 6 months after the attack, the type I, II, and III patients showed significant improvement (P < .05) in all language modalities compared with the type IV patients. Most improvement in language modalities occurred in the first 3 months. The evaluation of patients with ventricular rupture after 6 months revealed poor recovery (P < .05) in oral commands, visual commands, confrontation naming, sentence repetition, narratives, verbal fluency, and writing in type II and III patients. In type IV patients, this evaluation showed poor recovery (P < .05) only in oral and written naming (kanji words). No significant difference in prognostic outcome was observed between the surgical treatment group and the nonsurgical treatment group. The classification of hemorrhage may be useful in predicting the outcome of aphasia with putaminal hemorrhage and in guiding clinicians in providing effective instructions to patients and their relatives.


A new strain of rat with an inherited cataract.
A new rat strain has been developed, in which a spontaneous cataract occurs without exception at 3-4 months after birth and matures completely at 4-6 months of age, indicating that this rare strain possesses a maturity-onset cataract. In the present report, histological data are presented and discussed.


Impulsivity/sociability and reinforcement in verbal operant conditioning.
The present investigation was designed to study the relationship between impulsivity/sociability and modes of reinforcement in verbal operant conditioning. Two 2x3 randomized block designs, one each for impulsivity and sociability, were replicated ten times. One hundred and twenty undergraduate female students (60 for impulsivity and 60 for sociability) were individually subjected to Taffel's verbal conditioning procedure. When the conditioning scores of high and low scorers on the impulsivity and sociability scales were compared, it was found that under rewarding conditions ('good' and 'buzzer' in respect of sociability and 'good' in respect of impulsivity) the high scorers' score and under punishing conditions ('electric shock') the low scorers' score was the higher of the two. The study also revealed that the high scorers (on the impulsivity scale) conditioned more under rewarding conditions while the low scorers (both on the impulsivity and sociability scales) conditioned more under punishing ones.


Fluorescent and smartphone imaging detection of tetracycline residues based on luminescent europium ion-functionalized the regular octahedral UiO-66-NH2.
Antibiotic residues cause extensive damage to food security, thus arousing serious concerns. Hence, rapid and sensitive detection of antibiotic residues is crucial to food safety. This study aimed to propose a portable, visual, intelligent and rapid method for tetracycline detection. We developed a ratiometric fluorescent sensor based on the Eu3+-functionalized regular octahedral UiO-66-NH2 material. The developed sensor could quantify tetracycline in the concentration range of 0.5-200 μM with a detection limit as low as 0.2 μM under the optimum conditions. Furthermore, the analytical results obtained using the designed sensor in the actual samples were basically consistent with those obtained using high-performance liquid chromatography. Based on these achievements, a smartphone application-integrated fluorescent testing paper was designed for facile, intelligent, and visual detection of tetracycline. The integrated portable sensor not only saved cost and time for testing but also provided a forward-looking approach to fast, sensitive detection of antibiotic residues.


Ultrasound for Intubation Confirmation: A Randomized Controlled Study among Emergency Medicine Residents.
Confirmation of endotracheal tube (ETT) placement during intubation is a critical skill for emergency medicine (EM) residents; airway ultrasonography has been suggested as an accessible and accurate method of ETT confirmation. Here, we investigated the accuracy with which EM residents could identify ETT location in cadavers using different ultrasound modes. EM attendings intubated either the trachea or the esophagus of a cadaver, and blinded residents identified ETT position using either B-mode or B-mode plus color Doppler. Residents correctly identified ETT location in 1075 of 1203 trials (89.4%); performance improved with post-graduate year (residents in post-graduate year 3 had 97.8% accurate identifications). There were 556 (91.7%) correct identifications made with B-mode and 519 (86.9%) with B-mode plus color Doppler (p value = 0.007); thus, accuracy did not improve with addition of color Doppler to B-mode. Further research is needed on the efficacy of different ultrasound modes in confirming ETT placement in live intubations.


Responses of anterior pituitary hormones to heat exposure.
To determine anterior pituitary response to mild hyperthermia, plasma GH, ACTH, PRL and TSH were measured every 10 min in five subjects exposed to hot air (120 min, 50 C, 20 mbar) in a climatic chamber. Mean rectal temperatures increases of 0,8 C and mean sweat losses of 760 g were observed. GH levels increased from 4.4 +/- 0.4 ng/ml to 22.0 +/- 7.0 ng/ml (mean +/- SE) and reached maximum 80 min after the beginning of heat exposure and then declined before the end of the heat stress. These peak levels varied widely with the individual, whereas no significant changes in ACTH, PRL and TSH levels were observed during the exposure period. These results suggest that the mechanisms regulating GH secretion are more sensitive to an acute heat exposure than those of the other pituitary hormones studied.


Prevention of wound infection after elective colorectal resection.
Various operative wound handling techniques have been proposed to prevent wound infections after elective colorectal resection, including pelvic drains, wound wicks, topical antibiotics, and subcutaneous drains. Review of 243 consecutive elective colorectal resections performed between 1977 and 1983, in which 64 percent of the patients had significant underlying medical problems, 27 percent were over age 70, and 45 percent had concomitant abdominal procedures, revealed that consistent application of a uniform perioperative protocol emphasizing aseptic and antiseptic techniques minimizes wound and anastomotic infectious complications. Simple wound closure in this setting is sufficient to prevent incisional wound infections.


Sinovac vaccination and the course of COVID-19 disease in hospitalized patients in Turkey.
The Alpha variant of SARS-CoV-2 has a higher transmission rate than the first variant identified. The efficacy of vaccines is affected by the characteristics of SARS-CoV-2 variants. Investigate the relationship of vaccination and virus variant on the course of the disease in patients who were hospitalized with a diagnosis of COVID-19. Retrospective, cohort study SETTING: Tertiary health institution PATIENTS AND METHODS: The study included patients older than the age of 18 years who were hospitalized in a COVID-19 service or the intensive care unit with a diagnosis of COVID-19 between 1 January 2021 and 30 April 2021. Demographic characteristics, vaccination and the Alpha virus variant status, comorbidities, and information about hospitalization were obtained from the hospital automation system and patient files. Vaccination rate and relationship with course of disease. 608 RESULTS: Most of the patients (n=482, 79.3%) were admitted to the COVID-19 service. More of the COVID-19 service patients had the Alpha variant than the patients admitted to ICU (P<.009). The Alpha variant was also more common in younger patients (P<.001). There was no relationship between the Alpha virus and comorbid diseases such as diabetes mellitus and hypertension. Mortality was lower in the patients who had received a second dose of the Sinovac vaccine (P=.004) compared with unvaccinated patients. Although the Alpha variant spreads faster, it has a milder course. If only the Sinovac vaccine is available, we recommend that the two doses of the Sinovac vaccine be administered. Our study is single-center and did not include pregnant and pediatric patients. None.


Cytotoxicity and the levels of oxidative stress parameters in WI38 cells following 2 macrocyclic crown ethers treatment.
Crown ethers as macrocyclic polyethers possess a hydrophilic cavity surrounded by hydrophobic ring which enable them to diffuse cell membrane. We evaluated cytotoxicity effects of 15-crown-5 and 18-crown-6 and the role of oxidative stress in WI38 cells culture. The effect of these ethers in a range of doses (0.1 to 2 mmol/l) on the activity of antioxidant enzymes; superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase (CAT), and on some macromolecules oxidative damages end products; malondialdehyde (MDA) and dityrosine were assessed by spectrometry and HPLC methods. Both compounds markedly inhibited the viability of cells with respect to control particularly at doses >0.5 mmol/l after 24- or 48 h incubation. The survivals of cells were measured using MTT assay. They lowered cell's viability and significantly promoted ROS generation, increased enzyme activities and enhanced oxidative damages in which 18-crown-6 was more effective. Treating cells with 30 microm of alpha-tocopherol in addition to 2 mmol/l of crown ethers showed significant decrease on the levels of ROS, enzyme activities, MDA and dityrosine. We document the oxidative radicals forming ability of the studied crown ethers and further strengthens the documentation of their cytotoxicity effects through lipid and proteins oxidation damages.


Non-probabilistic time-variant reliability assessment (NTRA) for the active control of vibration systems with convex uncertainties.
Uncertainties, such as material dispersion, loading fluctuation and cognitive inconsistency, widely exist in active vibration control systems, and more importantly, the controller performance is generally sensitive to the parametric deviation. Thus, the uncertainty-oriented safety assessment for the controlled structure is of great significance in practical engineering. In view of the limitation of uncertain samples, a novel non-probabilistic time-variant reliability assessment (NTRA) approach, which combines the set-theoretical convex model and the first-passage method, is proposed for vibration suppression problems under the linear quadratic regulator (LQR) control scheme. Boundary rules and the time-dependency features of the controlled responses are first determined using the space-state transformation and the convex process theory. For safety reasons, a new time-variant reliability index is defined under the area-ratio principle, and its solution details are further discussed. Two engineering examples and one experimental case are presented to demonstrate the validity and applicability of the developed methodology.


Development, implementation, and feasibility of site-specific hepatitis C virus treatment workflows for treating vulnerable, high-risk populations: protocol of the Erase Hep C study - a prospective single-arm intervention trial.
Hepatitis C virus (HCV) is the leading indication for liver transplantation and liver-related mortality. The development of direct-acting antivirals (DAA) and a simplified treatment algorithm with a > 97% cure rate should make global elimination of HCV an achievable goal. Yet, vulnerable populations with high rates of HCV still have limited access to treatment. By designing locally contextualized site-specific HCV treatment workflows, we aim to cure HCV in vulnerable, high-risk populations, including people experiencing homelessness (PEH) and people who inject drugs (PWID), in Austin, TX, USA. Our implementation science study will utilize a qualitative and design thinking approach to characterize patient and systemic barriers and facilitators to HCV treatment in vulnerable, high-risk populations seeking care across seven diverse primary care clinics serving PEHs and PWIDs. Qualitative interviews guided by the Practical, Robust Implementation and Sustainability Model (PRISM) framework will identify barriers and facilitators by leveraging knowledge and experience from both clinic staff and patients. Data synthesized using thematic analysis and design thinking will feed into workshops with clinic stakeholders for idea generation to design site-specific HCV treatment workflows. Providers will be trained on the use of a simplified HCV treatment algorithm with DAAs and clinic staff on the new site-specific HCV treatment workflows. These workflows will be implemented by the seven diverse primary care clinics serving vulnerable, high-risk populations. Implementation and clinical outcomes will be measured using data collected through interviews with staff as well as through medical chart review. Our study provides a model of how to contextualize and implement site-specific HCV treatment workflows targeting vulnerable, high-risk populations in other geographic locations. This model can be adopted for future implementation research programs aiming to develop and implement site-specific treatment workflows for vulnerable, high-risk populations and in primary care clinical settings for other disease states beyond just HCV. Registered on ClinicalTrials.gov on July, 14, 2022. Identifier: NCT05460130 .


Levels and Distribution of Organophosphate Esters (OPEs) in Typical Megacity Wetland Park Landscape Water Bodies in Southwest China.
Human activities have led to the release of organophosphate esters (OPEs) into the environment. This study aims to investigate the levels and partitioning of OPEs in surface water, suspended particulate matter (SPM) and sediments of landscape waters across eleven parks in the city of Chengdu, a megacity in Southwest China. The average concentration of Σ6OPEs in the SPM samples (median: 2.94 × 103 ng/L, 6.88 × 104 ng/g dry weight) was 1-3 orders of magnitude higher than that in the surface water (median: 359 ng/L) and sediment (median: 82.8 ng/g) samples. Tri-n-butyl phosphate (TnBP), tris-(2-chloroethyl)-phosphate (TCEP) and trichloropropyl phosphate (TCIPP) were the primary OPE pollutants in the surface water and SPM samples, while TnBP, tris-(2-butoxyethyl) phosphate (TBEP) and tris-(2-ethylhexyl) phosphate (TEHP) predominated the sediment samples. The higher log Koc values of OPEs in park landscape water bodies estimated in the present study relative to previous studies could be explained by the environmental conditions, such as the sources of the inputs and the hydraulic retention times in these surface waters.


The association between cheese consumption and cardiovascular risk factors among adults.
Although current dietary guidelines recommend limiting foods high in fat and saturated fat, such as high-fat dairy, the effect of cheese consumption on body composition and cardiovascular risk factors is largely unknown. Participants from a US population-based survey, NHANES III, aged 25-75 years who completed a food frequency questionnaire and had measures of body composition and cardiovascular risk factors were included (n = 10 872). Linear regression was used to compare anthropometrics, blood lipids, blood pressure and blood glucose across categories of cheese consumption (combined full and low-fat). In women, more frequent cheese consumption was associated with higher HDL-C and lower LDL-C (p for trend, < 0.05). However, in men, more frequent cheese consumption was associated with a higher body mass index (BMI), waist circumference, HDL-C and LDL-C, and diastolic blood pressure (p for trend, < 0.05). Men consuming 30 + servings/month had significantly higher BMI, waist circumference, and diastolic blood pressure compared to nonconsumers (P < 0.05). More frequent cheese consumption was associated with less favourable body composition and cardiovascular risk profile in men, but with a more favourable cardiovascular risk profile in women. However, the type of cheese consumed by men and women may have differed resulting in opposing trends on body composition and cardiovascular risk factors.


Morphine reduces vagal-stimulated gastric acid secretion through a central action.
The influence of morphine on gastric acid secretion stimulated by 2-deoxy-D-glucose or electrical vagal stimulation was studied in anaesthetised rats with perfused stomachs. It was found that changes in gastric acid output induced by electrical vagal stimulation were not noticeably affected, whereas those evoked by 2-deoxy-D-glucose were significantly suppressed by morphine pretreatment. The depressant effect of the opiate on the acid secretion stimulated by 2-deoxy-D-glucose was abolished by naloxone pretreatment. It is suggested that morphine inhibits vagal-stimulated gastric acid secretion in rats by acting predominantly on opioid receptors in the central nervous system.


Evaluation of anti-sepsis activity by compounds with high affinity to lipid a from HuanglianJiedu decoction.
HuanglianJiedu decoction (HJD) is a classic prescription for heat-clearing away and detoxifying, which is used for the clinical treatment of sepsis, due to sepsis refers to the systemic inflammatory response induced by infection in western medicine, and infection belongs to the category of poison-heat syndrome in traditional Chinese medicine. Previous study had elucidated the effective components from HJD with high affinity to lipid A, which can generate the release of pro-inflammatory-cytokines, resulting in sepsis. Now the anti-sepsis activities of these compounds were evaluated. Immunofluorescence, immunohistochemical staining, ELISA and MTT methods were used to evaluated these compounds. Immunofluorescence analysis evaluated the effects of compounds on the binding of FITC-LPS to RAW264.7 cells, and showed the fluorescence intensity was significant attenuated in geniposides, palmatine, baicalin and berberine groups (64 and 128 μg/mL) compared with model group (p < 0.05), which showed these compounds inhibit the combination of LPS with receptor of cells; immunohistochemical staining and ELISA method showed the TLR4 receptor expression, IL-6 and TNF-α levels were significant decreased in the groups treated with compounds, indicating that geniposides, baicalin, palmatine and berberine can play the role of anti-sepsis by inhibiting the expression of TLR4, the releasing of IL-6 and TNF-α; MTT assay showed that palmatine and berberine had a weak effect on cell viability, while others not, indicating that the compounds have protective activity. It could be concluded the high affinity binding between these compounds and lipid A may be an important basis for its anti-LPS activity in vitro.


Effects of cumene hydroperoxide on cellular cation composition in frog kidney proximal tubular cells.
Effects of cumene hydroperoxide were studied on the peritubular membrane potential and cellular cation composition in frog kidney proximal tubular cells. After perfusion of isolated frog kidneys for 30 min with 1.3x10(-4) mol l(-1) cumene hydroperoxide Ringer solution, the peritubular membrane potential gradually declined. The ouabain-like effects were demonstrated on cell Na and K activities after 1 h of perfusion with cumene hydroperoxide. The peritubular apparent transference number for potassium was decreased. Intracellular pH was not altered in the presence of cumene hydroperoxide. Intracellular free Ca(2+) concentration increased slowly and moderately. The concentration of the malondialdehyde in the kidney homogenates, measured as an index of lipid peroxidation, was increased. A previously observable effect of cumene hydroperoxide on the peritubular membrane potential was prevented by oxygen radical scavengers.


The influence of aspirin dose and glycemic control on platelet inhibition in patients with type 2 diabetes mellitus.
Low-dose aspirin seems to offer no benefit in the primary prevention of cardiovascular disease in type 2 diabetes mellitus (DM2). The anti-platelet effect may be diminished by poor glycemic control or inadequate dosing of aspirin. To study the effects of both glycemic control and increasing aspirin dose on platelet response to aspirin in DM2 patients and matched controls. Platelet effects of increasing doses of aspirin (30, 100 and 300 mg daily) were prospectively assessed in 94 DM2 patients and 25 matched controls by measuring thromboxane levels in urine (11-dhTxB2) and platelet aggregation using VerifyNow(®) and light transmission aggregometry (LTA). DM2 patients were stratified for glycemic control (hemoglobin-A1c [HbA1c] ≤ 53, 53-69, ≥ 69 mmol mol(-1)). At baseline, median 11-dhTxB2 excretion was higher in the poorly controlled patients (77 ng mmol(-1)), and the moderately controlled (84 ng mmol(-1)) compared with the well-controlled patients (64 ng mmol(-1)) and controls (53 ng mmol(-1)), P < 0.01. Next, 30 mg of aspirin reduced 11-dhTxB2 excretion to 31, 29 and 24 ng mmol(-1) in the poorly, moderately and well-controlled patients, respectively, and to 19 ng mmol(-1) in controls, P < 0.001. VerifyNow(®) and LTA were also incompletely suppressed in DM2 patients using 30 mg of aspirin, but 100 mg resulted in similar platelet suppression in all groups, with no additional effect of 300 mg. DM2 patients with inadequate glycemic control (HbA1c > 53 mmol mol(-1)) have higher baseline platelet activity and incomplete suppression of platelet activity with 30 mg of aspirin. However, 100 mg of aspirin leads to optimal inhibition irrespective of glycemic control, and 300 mg does not further improve platelet suppression.


Spectral characteristics of ortho, meta and para dihydroxy benzenes in different solvents, pH and beta-cyclodextrin.
Spectral characteristics of ortho, meta and para dihydroxy benzenes (DHB's) have been studied in different solvents, pH and beta-cyclodextrin. Solvent study shows that: (i) the interaction of OH group with the aromatic ring is less than that of amino group both in the ground and excited states, (ii) in absorption, the charge transfer interaction of OH group in para position is larger than ortho and meta positions. pH studies reveals that DHB's are more acidic than phenol. The higher pK(a) value of oDHB (monoanion-dianion) indicates that the formed monoanion is more stabilized by intramolecular hydrogen bonding. DHB's forms a 1:1 inclusion complex with beta-CD. In beta-CD medium, absorption spectra of DHB's mono and dianions shows unusual blue shifts, whereas in the excited state, the spectral characteristics of DHB's follow the same trend in both aqueous and beta-CD medium.


Fiberoptic bronchoscopy combined with selective bronchography. A simplified technique.
Since bronchography is helpful in certain clinical settings, we describe a simplified method for performing selective bronchography in conjunction with fiberoptic bronchoscopy. Selected cases are presented which illustrate that this technique is easily performed, has minimal risk, and produces bronchograms of high quality.


Mid-Term Evolution of the Serum Acylcarnitine Profile in Critically Ill Survivors: A Metabolic Insight into Survivorship.
It is unknown if the abnormal acylcarnitine (AC) profile observed early after discharge of a prolonged stay in an intensive care unit (ICU) would persist over time. This prospective observational study aimed to describe the mid-term AC profile evolution in survivors of a prolonged ICU stay (≥7 days). Adults enrolled in our post-ICU follow-up program and who attended the consultation 3 months (M3) after discharge were included. Serum AC concentrations were assessed within 7 days following ICU discharge (T0) and at M3. A total of 64 survivors were analyzed after an ICU stay of 15 (9-24) days. Free carnitine (C0) concentration decreased from 45.89 (35.80-127.5) to 28.73 (20.31-38.93) µmol/L (p < 0.001). C0 deficiency was not observed at T0 but in 7/64 (11%) survivors at M3. The total AC/C0 ratio (normal ≤ 0.4) was 0.33 (0.24-0.39) at T0 and reached 0.39 (0.30-0.56) at M3 (p = 0.001). A ratio >0.4 was observed in 16/64 (25%) at T0 and in 32/64 (50%) at M3 (p = 0.006). The short-chain ACs decreased from 1.310 (0.927-1.829) at T0 to 0.945 (0.709-1.127) µmol/L at M3 (p < 0.001). In parallel, the urea/creatinine ratio and the Sarcopenic Index, respectively, decreased and increased between T0 and M3. This AC profile is suspected to signal a mitochondrial dysfunction and was, especially for short-chain ACs, a marker of protein catabolism.


New chiral 4-substituted 2-cyanoethyl-oxazolines: synthesis and assessment of some biological activities.
This paper describes the synthesis of new enantiomerically pure 2-cyanoethyl-oxazolines in one step starting from a wide range of amino alcohols and 4-ethoxy-4-iminobutanenitrile with high to good yields (73-96%) via an appropriate procedure which can be used for a selective synthesis of mono-oxazolines. A simple operation as well as a practical separation is additional eco-friendly attributes of this method. All the synthesized compounds were identified and characterized with their physicochemical features and their spectral data ((1)H NMR, (13)C NMR and TOFMS ES(+)). Among the prepared mono-oxazolines, the mono-oxazoline (3a) [3-[(4S)-4-benzyl-4,5-dihydro-1,3-oxazol-2-yl] propanenitrile] was tested to detect some biological activities. This compound was studied in vitro given the various types of pharmacological properties characterizing these compounds such as antioxidant, antimicrobial and analgesic activities. The antioxidant activity and mechanism of (3a) were identified using various in vitro antioxidant assays including 1,1-diphenyl-2-picryl-hydrazyl (DPPH), and superoxide anion radicals (O2(-)) scavenging activity. In addition, compared to Quercetin, the tested synthetic product reveals a relatively-strong antiradical activity towards the DPPH (activity percentage of 81.22%) free radicals and significantly decreased the reactive oxygen species such as (O2(-)) formation evaluated by the non-enzymatic (nitroblue tetrazolium/riboflavine) and the enzymatic (xanthine/xanthine oxidase) systems. Related activity values were, respectively, 66% and 60.30%. The oxazoline (3a) showed a high ability to reduce the O2(-) generation and proved to be a very potent radical scavenger. On the other hand, the analgesic property of the 3[(4S)-benzyl-4,5-dihydro-1,3-oxazol-2-yl] propanenitrile (3a) was demonstrated. The subcutaneous administration of (3a) produced a significant reduction in the number of abdominal constrictions amounting to 73.81% in the acetic acid writhing test in mice. In addition to these advances, the oxazoline (3a) has been investigated as an antimicrobial agent. Our results showed that this molecule exhibited various levels of antibacterial effect against all the tested bacterial strains.


Let-7g inhibits synthesis of estradiol by downregulating activity of aromatase in JEG3 cells.
Increased production of estrogen in human placenta during pregnancy closely associates with parturition. Aromatase, encoded by CYP19A1 gene, is an enzyme critical for biosynthesis of estrogen. Despite numerous efforts in the past few decades ascribed to characterizing the mechanisms of transcriptional control of aromatase, the posttranscriptional control of CYP19A1 remains poorly understood. In this study, we sought to investigate the role of microRNA, let-7g, in posttranscriptional regulation of aromatase in human trophoblast choriocarcinoma cell line, JEG3. We show that the expression of let-7g was downregulated in JEG3 cell line, but upregulated in primary term trophoblast; conversely, aromatase was upregulated in JEG3 but downregulated in primary trophoblast. We further show that let-7g antagomirs and mimics increased and decreased aromatase expression, respectively; and let-7g directly targeted 3'-untranslated region of CYP19A1 mRNA by using dual luciferase assay. Using ELISA, we also demonstrate that let-7g antagomirs and mimics robustly increased and decreased production of estradiol, respectively. Our results suggest that aromatase expression is regulated at multiple molecular layers in the placenta. These results further suggest that JEG3 cell line is a valuable tool to study additional mechanisms associated with human birth.


A phase II trial of docetaxel and bevacizumab in recurrent ovarian cancer within 12 months of prior platinum-based chemotherapy.
The efficacy and safety of bevacizumab and docetaxel were evaluated in women who developed recurrent epithelial ovarian, fallopian, or peritoneal cancer within 12 months of platinum-based therapy. Patients received docetaxel (40 mg/m(2)) on days 1 and 8 and bevacizumab (15 mg/kg) on day 1 of a 21-daycycle. Primary endpoint was 6-month progression-free survival (PFS). Forty-one patients were evaluable for PFS and 38 for best response; 46% had platinum-free intervals (PFI) of <6 months and 54% between 6 and 12 months. The 6-month PFS was 43.9% (95% confidence interval (CI(95%))=28.6-58.2%). Median PFS (months) was 5.2 (CI(95%)=4.4-7.2) for all patients, 6.2 (CI(95%)=4.1-7.4) for patients with PFI <6 months, and 5.1 (CI(95%)=3.0-7.2) for those with PFI ≥ 6 months. Twenty-two patients showed overall response (CR+PR) (57.9%; CI(95%)=40.8-73.7%), and 32 showed clinical benefit (CR+PR+SD) (84.2%; CI(95%)=68.8-94.0%). For those with complete or partial responses, median duration of response was 4.8 months (0.7-14.5). Median overall survival was 12.4 months (CI(95%)=10.0-21.9). The most common grade 3/4 adverse events (AEs) were neutropenia (14.6% of patients), followed by leukopenia, fatigue, metabolic, and gastrointestinal, with 66% showing any grade 3/4 toxicity. Most common AEs of any grade were gastrointestinal (93%), fatigue (73%), and pain (73%). Four (10%) patients developed hypertension, 1 a gastrointestinal perforation, and another a colovesicular fistula. Bevacizumab and docetaxel administered in patients with recurrent ovarian cancer is an active regimen without new unanticipated toxicities. This combination should be an option for further study or clinical use in recurrent ovarian cancer.


Assessment of gill pathological responses in the tropical fish yellowfin seabream of Persian Gulf under mercury exposure.
Gill histomorphological alterations were used to assess the effects of chronic exposure to HgCl2 on the yellowfin seabream, Acanthopagrus latus. In this regard, 90 A. latus were exposed to sublethal concentrations of HgCl2 (10, 20, 35 and 50 μg/L) for 3 weeks. Treated fish were erratic and showed respiratory distress. The most common morphological abnormalities included: filaments disorganization, increase of mucus secretion, debris and blood plaques on the filaments, losing or shortening of some filaments. The most frequent histopathological changes detected in the gills included extensive lifting of the lamellar epithelium and edema of lamellae with enlarged sub-epithelial spaces, exfoliated epithelium of lamellae, telangiectasia, hypertrophy and hyperplasia of the epithelial cell resulted in partial fusion of the secondary lamellae and a reduction of the water space, club shaping of gill lamellae, blood congestion. Some more severe alternations found in the gill of fish exposed to higher levels of HgCl2 (35 and 50 μg/L) included lamellar aneurysm and hemorrhages with rupture of the lamellar epithelium. According to the results of the present study, mercuric chloride could cause major histomorphological changes in the gill of A. latus, decreasing its gas exchange capability. Two mercury concentrations (10 and 20 μg/L) used in the present study were in agreement with the concentration of mercury in the water of different parts of Mahshahr creeks (the north of Persian Gulf) (3.66 to 15 μg/L). Therefore, based on the results the presence of pathological alteration in A. latus inhibited in the natural environment (Mahshahr creeks) seems to be logical.


Adult cervicothoracic subpial fibrolipoma without dysraphism: An extremely rare case report.
Spinal tumors constitute 15 % of all tumors in the central nervous system. Pain is often the initial symptom, which can be localized, nocturnal, or radiated to the arms and/or limbs. We report a rare case with a subpial lipoma in the cervicothoracic spine and review the current literature. A 22-year-old female presented with the chief complaint of tetraparesis for three months before admission. Magnetic resonance imaging revealed an intradural tumor on the fifth cervical to fourth thoracic vertebrae. She underwent a laminectomy to remove the tumor completely. Histopathological examination revealed a proliferation of mature fat cells amongst fibrous connective tissue. Surrounding nerve fibers and erythrocyte-filled blood vessels were also found, suggesting a subpial fibrolipoma. Postoperatively, there was an improvement in muscle strength six weeks after surgery. Motoric strength was grade 5 for the upper extremities and grade 4 for the lower extremities. In this patient, cervicothoracic laminectomy and tumor removal were performed without instrumentation. Total tumor resection is the primary goal when removing a pathological lesion. However, this depends on the lesion's adhesion to the surrounding tissue. Therefore, partial tumor resection may be possible, given the neurological complications that can occur. Because subpial lipomas are rare, their treatment is highly specialized. An assessment of the patient's physical condition and imaging assessments can provide information about potential treatment strategies and outcomes.


Myrmecofauna of ironstone outcrops: composition and diversity.
The Iron Quadrangle in the state of Minas Gerais, Brazil, harbors ironstone outcrops locally known as cangas, which are historically under great anthropic pressure. The functions performed by ants in environments with severe edapho-climatic conditions, such as cangas, are poorly known. Considering the lack of studies and the potential role of ants in cangas, this study aimed to identify the taxonomic composition of the myrmecofauna that occurs in the soil of two campo rupestre areas (rupestral plant communities) on cangas under different anthropic impacts and evaluate the influence of seasonality and degree of degradation on the diversity and composition of the myrmecofauna. This is the first study to systematically investigate ant fauna collected with baits on ironstone outcrops. Sardine and honey baits were used in dry and rainy periods. Fourteen species distributed among ten genera belonging to five subfamilies were found. The total number of baits visited in the dry season was lower than in the rainy season. Both habitats had a reasonable similarity in their composition (Jaccard similarity index = 0.571). Multivariate analyses suggest a greater similarity between areas than seasons. The diversity of ants in the cangas is low compared to other Cerrado environments where more than 20 species are frequently collected in these types of study. This low richness may be related to the adverse conditions characteristic of ironstone outcrops. We hope our data will help to expand the actions to manage and preserve cangas in the Iron Quadrangle.


[Complication management after bile duct surgery].
Bile leakage and postoperative bile duct strictures or anastomotic stenosis after bilioenteric anastomosis are complex surgical complications, which are associated with increased morbidity and mortality. Detailed diagnostics and sophisticated decision-making is always requiered. Complex liver surgery (redo procedures, nonanatomic resections, etc.) and surgery involving the liver hilum or exposure of the intraparenchymal Glissonean sheath are risk factors for postoperative bile leakage. Bile leakage is defined as a bilirubin concentration at least three times greater than the serum bilirubin measured in an abdominal drainage on or after the third postoperative day or as the need for radiologic intervention because of biliary collection or relaparotomy for bile peritonitis. Therapeutic strategies for bile leakage comprise conservative watch and wait, interventional procedures (endoscopic or percutaneous biliary drainage) and relaparotomy and are selected based on the postoperative onset, output volume and anatomic localization of the bile leak. Conservative treatment and interventional procedures show a high success rate and should therefore be considered as the treatment of choice in most cases. In contrast to bile leakage, bile duct strictures and anastomotic stenosis are rarely observed after surgery and can usually be treated by interventional procedures. This review article discusses situation-dependent specific treatment of postoperative bile leakage as well as bile duct strictures and anastomotic stenosis in detail.


Verapamil does not modify catalytic activity of CYP450 in rainbow trout after long-term exposure.
Little is known about the effects of the cardiovascular drug verapamil (VRP) on metabolic processes in fish. Most calcium channel blockers including VRP are metabolized by cytochrome P450 (CYP450) enzymes. In this study we investigated the in vivo effect of VRP on some CYP450-mediated reactions in juvenile rainbow trout (Oncorhynchus mykiss). Fish were exposed to sublethal concentrations of VRP (0.5, 27 and 270 μg l(-1)) for 0, 21, and 42 day. The following CYP450-mediated reactions were studied in hepatic microsomes: O-dealkylation of ethoxyresorufin, methoxyresorufin, and pentoxyresorufin, hydroxylation of coumarin, tolbutamide, and p-nitrophenol, and O-debenzylation of 7-benzyloxy-4-trifluoromethylcoumarin. The amounts of products of these reactions did not differ among fish exposed to different levels of VRP and control fish. This suggests that the levels of VPR used did not alter catalytic activity of the selected CYP450 enzymes. In conclusion, none of the investigated CYP450-mediated reactions has potential as a biomarker to monitor VRP contamination of the aquatic environment.


Report from the second Japanese Urological Association-Japanese Society of Medical Oncology joint conference, 2007: 'diagnosis and treatment of urological malignant tumors: how can we promote subspecialists?'.
The second Japanese Urological Association-Japanese Society of Medical Oncology joint conference was held on 25 October 2007. The theme of this year's conference was 'Diagnosis and treatment of urological malignant tumors: How can we promote subspecialists?' This Meeting Report briefly discusses the themes of uro-oncology education; collaboration of urologists and medical oncologists for treatment of advanced renal cell carcinoma; the role of urologists in treatment of urological cancer; the role of the medical oncologist in therapy, and collaboration between the JUA and the JSMO.


Lignin and ethylcellulose in controlled release formulations to reduce leaching of chloridazon and metribuzin in light-textured soils.
In this research, controlled release formulations (CRFs) of the herbicides chloridazon and metribuzin, identified as potential leachers, have been evaluated in soils with different texture. To prepare the CRFs, ethylcellulose (EC) and dibutylsebacate (DBS) have been used as coating agents in lignin-polyethylene glycol based formulations. Mobility experiments have been carried out in two light textured soils (sandy and sandy-loam). Breakthrough curves have shown that the use of CRFs reduces the presence of chloridazon and metribuzin in the leachate compared to technical and commercial products, being the lignin CRF coated with EC and DBS the most efficient to diminish the herbicide leaching. Mass balance study has shown a higher amount of chloridazon and metribuzin recovered in soils when these herbicides were tested as CRFs compared to technical and commercial products. The gradual release of herbicides from the CRFs resulting in a rather available levels of chloridazon and metribuzin in soil for a longer time. A good correlation between percentages of herbicide recovered in leachates and T50 values (time corresponding to 50% release of herbicide in water) was obtained, which allows to select the most appropriate CRF in each agro-environmental practice to reduce the potential pollution of groundwater by chloridazon and metribuzin.


Renal-clearable and biodegradable black phosphorus quantum dots for photoacoustic imaging of kidney dysfunction.
The kidney is a vital organ and susceptible to various diseases. Photoacoustic (PA) imaging provides a powerful technique for studying kidney dysfunction, for which many smart photoacoustic imaging agents have been developed. But the complete clearance of the introduced contrast agents after imaging remains to be challenging, leading to long-term toxicity concerns. In this study, we synthesized black phosphorous quantum dots (BPQDs) with ultra-small size (1.74 ± 0.23 nm after surface modification) and strong PA signal for imaging kidney dysfunction. Importantly, the renal-clearance property and biodegradability of the developed BPQDs help circumvent the long-term toxicity issue for in vivo studies. Based on these BPQDs, both acute kidney injury and chronic kidney disease were successfully detected in the living mice by PA imaging, with higher detection sensitivity than the clinical serum indices examination method. This BPQDs-based PA imaging method should have a promising potential for the early diagnosis of kidney dysfunction in clinic.


The role of nitric oxide in tendon healing.
Nitric oxide (NO) is a small free radical that is generated by a family of enzymes called the nitric oxide synthases (NOS). There are 3 isoforms of NOS: endothelial NOS (eNOS), brain or neuronal NOS (bNOS), and inducible NOS (iNOS). In experiments performed during the last 20 years, we have shown that NO is induced by all 3 isoforms of NOS after tendon injury and that NOS activity is upregulated in tendinopathy. In normal uninjured tendons, there is very little NOS activity. In injured rat and human tendons, NOS activity was found in healing fibroblasts in a temporal fashion. In animal models, competitive inhibition of NOS resulted in reduced tendon healing, whereas the addition of NO resulted in enhanced tendon healing. In cultured human cells, the addition of NO via chemical means and adenovirus transfection resulted in enhanced collagen synthesis. We performed 3 randomized, double-blinded clinical trials that demonstrated a significant positive beneficial effect of NO treatment on clinical symptoms and function in patients with Achilles tendinopathy, tennis elbow, and supraspinatus tendonitis. NO was delivered via glyceryl trinitrate (GTN) patches. We also conducted a 3-year prospective follow-up that demonstrated significant long-term efficacy of GTN patches in treating noninsertional Achilles tendinopathy. In a 5-year prospective comparison treating lateral epicondylitis, we found no additional benefits of GTN vs placebo at 5 years. The use of a new GTN patch, OrthoDerm, demonstrated no evidence for efficacy in treating chronic lateral epicondylitis.


Role of Teleproctoring in Challenging and Innovative Structural Interventions Amid the COVID-19 Pandemic and Beyond.
Teleproctoring can be used successfully in performing challenging and innovative structural heart interventions using sophisticated technology that allows real-time bidirectional audiovisual communication with digital transmission of live videos and direct observation of the operative field by a remote proctor. The authors share an illustrative case that was performed amid the coronavirus disease-2019 global pandemic that led to travel restrictions to limit spread of the virus. Teleproctoring has future implications beyond the current global health crisis to facilitate rapid dissemination and exchange of knowledge for ultimately helping patients around the globe.


The dyslipoproteinemia of anabolic steroid therapy: increase in hepatic triglyceride lipase precedes the decrease in high density lipoprotein2 cholesterol.
Administration of the androgenic anabolic steroid, stanozolol, is associated with decreased high density lipoprotein (HDL) cholesterol (primarily due to decreased HDL2 cholesterol) and increased levels of postheparin plasma hepatic triglyceride lipase (HTGL) activity. Since HTGL appears to play a role in HDL metabolism, we examined the temporal relationship between these changes. HDL cholesterol remained stable during the first two days of stanozolol administration, but decreased 14% (P less than .01) by the third day and 39% (P less than .01) by the seventh day of stanozolol. HDL2 cholesterol paralleled the total HDL cholesterol level and remained stable for the first two days, but decreased 22% (P less than .01) after three days and 71% (P less than .01) after seven days of stanozolol. In contrast, HTGL increased 62% (P less than .001) during the first day, 161% (P less than .001) with two days, 230% (P less than .001) with three days of stanozolol administration, and remained elevated thereafter. Thus, during stanozolol administration HTGL increased dramatically and clearly before any change in HDL or HDL2 cholesterol.


Comparison of regional pulmonary perfusion in lobar pneumonia during high frequency and conventional mechanical ventilation in sheep.
We compared the effects of high frequency jet ventilation (HFV), conventional ventilation (CMV), and spontaneous breathing (SB) on regional pulmonary blood flows (QLLL), standard cardiopulmonary measurements and the serum levels of the first generation metabolites of prostacyclin (6-keto-PGF1 alpha) and thromboxane A2 (TxB2) in established left lower lobe pseudomonas aeruginosa pneumonia in 11 sheep. Gram negative pneumonia resulted in significant increases in alveolar-arterial oxygen gradients [(A-a)DO2] and pulmonary shunt fractions (Qs/Qt), as well as a significant decrease in QLLL during SB. Significant differences in standard haemodynamics, (A-a)DO2, Qs/Qt, and QLLL were not observed when HFV was compared to CMV. However, serum levels of 6-keto-PGF1 alpha were elevated when the animals underwent HFV. We conclude that HFV is a safe and efficient method of oxygenation and ventilation in unilobar gram negative pneumonia and also results in a significant increase in the serum levels of 6-keto-PGF1 alpha when compared to CMV in sheep. The exact significance of the latter finding is the subject of current investigation.


Epidemiological investigation of a case of malaria in a non-endemic area, Campo de Gibraltar, Cadiz, Spain, January 2022.
We describe a non-imported malaria case reported in January 2022 in Campo de Gibraltar and the investigations by local public health authorities to identify the transmission mechanism and subsequent measures to prevent local transmission. Vector transmission, parenteral transmission, airport malaria, and imported malaria were ruled out. No clear mechanism of transmission was identified. The most probable cause was a hospital-acquired infection since the case was admitted to hospital at the same time as a case of imported Plasmodium falciparum malaria.


The case against volume as a measure of quality of surgical care.
Healthcare purchasers, represented by the Leapfrog Group, have attempted to set standards for "quality" of surgical care that include a minimum volume for each of five major surgical procedures, with the assumption that higher volumes in surgery bring better outcomes. The VA National Surgical Quality Improvement Program (NSQIP) is a validated, outcome-based program that prospectively collects clinical data on all major surgical operations in the VA, and builds validated risk-adjustment models that generate, for each hospital and each surgical specialty within a hospital, risk-adjusted outcomes expressed as O/E (observed to expected) ratios for 30-day mortality and morbidity. The O/E ratio has been validated as a reliable comparative measure of the quality of surgical care. Unlike retrospective studies that are based on administrative databases, NSQIP studies have failed to demonstrate a direct relationship between volume and risk-adjusted outcomes of surgery across various specialties. These studies have emphasized that the quality of systems of care was more important than volume in determining the overall quality of surgical care at an institution. High-volume hospitals could still deliver poor care in as much as low-volume hospitals could deliver good care. NSQIP studies have also underscored the major limitations of claims data and administrative databases in the provision of adequate risk-adjustment models that are crucial for volume-outcome studies. Therefore, volume should not be substituted for prospectively monitored and properly risk-adjusted outcomes as a comparative measure of the quality of surgical care.


Induction of multiple shoots from leaf segments, in vitro-flowering and fruiting of a dwarf tomato (Lycopersicon esculentum).
Multiple shoots were induced from leaf explants of Lycopersicon esculentum cultivar MicroTom, within 20-25d, on MS medium supplemented with 8.9 microM benzylaminopurine (BAP)+1.14 microM indole-3-acetic acid (IAA). For rooting, elongated microshoots were excised and transferred onto MS medium supplemented with 4.9 microM indole-3-butyric acid (IBA). Well-developed roots and flower raceme were obtained on d 7 and 13, respectively, upon transfer of the microshoots onto rooting medium. The flowers self-fertilized in vitro and produced mature fruits in additional 15-17d of culture.


Application of micro-electrospray liquid chromatography techniques to FT-ICR MS to enable high-sensitivity biological analysis.
A microbore electrospray (ESI) injection system has been adapted to our 9.4-tesla ESI FT-ICR mass spectrometer, greatly enhancing the stability and sensitivity of the system. Spray was generated from micro-ESI needles made from sharply tapered, polished fused silica capillaries of 25 to 50 microns inner diameter. Micro-ESI permits low-level sample analysis by constant infusion at sub-microL/min flow rate over a wide range of solvent conditions in both positive- and negative-ion mode. The system is flexible and allows rapid conversion to allow routine LC/MS analysis on low-level mixtures presented in biological media. LC/MS analyses were accomplished by replacing micro-ESI needles with capillaries packed with reverse phase retention media to permit analyte concentration and purification prior to analysis (micro-ESI/LC). A unique nano-flow LC pumping system was developed, capable of producing a true unsplit solvent gradient at flow rates below 1 microL/min. The micro-ESI/LC FT-ICR system produces mass spectra from a mixture of three neuroactive peptides at a concentration of 500 amol/microL (5 fmol each total loaded) in biological salts with baseline separation, signal-to-noise ratio of > 10:1 and mass resolving power > 5000. These results represent a reduction in detection limit by a factor of approximately 2 x 10(6) over the best previously published LC/FT-ICR MS data.


Complete Genome Sequence of Deformed Wing Virus Isolated from Vespa crabro in Italy.
In this article, we document the first isolation of a replication-competent deformed wing virus from Vespa crabro in Italy. Although the virus has never been isolated from this insect, the sequence of this virus shows a strong sequence homology with isolates obtained from Apis mellifera, which is considered its natural host.


Spontaneous thrombolysis of native artery occlusions.
Acute arterial ischemia of the lower extremities is a major cause of mortality and limb loss in patients with peripheral vascular disease. Patients with acute limb ischemia secondary to embolus or in situ thrombosis usually require emergency revascularization, either surgically or with the use of thrombolytic agents. It is commonly assumed that heparin therapy alone, without disobliterative intervention, can produce clinical improvement through continued patency and enlargement of the collateral circulation. The occurrence of spontaneous thrombolysis of major limb vessels is not generally accepted. We describe three patients, all with confirmed occlusion of either the iliac or superficial femoral arteries, who had spontaneous thrombolysis of occluded vessels. These experiences document that spontaneous resolution of arterial occlusion does occur, although it may be infrequent.


[An accessory retropharyngeal bone as a rare cause of dysphagia].
A 77-year-old woman had a history of several-years of dysphagia. On presentation, a submucosal mass impinging on the left oropharynx was present. CT-scans showed a bony structure isolated from the cervical column. The patient underwent complete surgical resection using a transoral approach. Histological examination confirmed the radiological finding; a new formation of bone surrounded by cartilage with hematopoieses in the bone marrow. Recovery was complete within 2 weeks. Dysphagia due to cervical spine osteophytes, Forestier's disease or progressive ossifying fibrodysplasia is well known. This case adds an isolated retropharyngeal bone formation as a rare cause of dysphagia to the literature.


National Trends and Cost of Minimally Invasive Surgery in Urology.
We determine national trends in costs of care as well as associated growth and adoption of minimally invasive surgery for major uro-oncology procedures. Using a nationally representative sample we identified patients diagnosed with prostate, renal and bladder cancer who underwent prostatectomy, nephrectomy, partial nephrectomy and cystectomy from 2000 to 2011. Temporal trends in patient demographics, hospital and procedure related characteristics, surgical volume, minimally invasive surgery use and costs of hospitalization over the years were analyzed. Hierarchical linear regression was performed to evaluate the effects of hospital volume, time and surgery type on costs of hospitalization. Overall 836,563, 440,337 and 122,992 patients underwent prostatectomy, nephrectomy and cystectomy from 2000 to 2011, respectively. There was a 33.6%, 50.8% and 25.5% increase in annual surgical volume for these 3 surgeries during the 10 years, with the most prominent increase at high volume hospitals. The use of minimally invasive surgery increased 65.6% for prostatectomy, 22.0% for nephrectomy and 12.5% for cystectomy, and this increase was more prominent at high volume hospitals. For all 3 surgeries the hospital stay for minimally invasive surgery cases was more expensive than for open procedures, but decreased during the study period from $17,367 to $11,145 for prostatectomy and from $54,209 to $28,753 for cystectomy. High volume hospitals experienced greater growth in surgery caseloads and minimally invasive surgeries but this did not lead to higher costs of care. While minimally invasive surgery has consistently been more expensive than open surgery, the costs of minimally invasive prostatectomy and cystectomy have decreased in the last decade.


Degradation of myelin basic protein by calcium-activated neutral protease (CANP) in human brain and inhibition by E-64 analogue.
A calcium-activated neutral protease (CANP) was extracted from human brain and partially purified. The activity was measured using alkali-denatured casein (Hammersten) as a substrate. The optimum pH was around 7.0. The activity required the presence of calcium ions, maximum activity was obtained with over 5 mM calcium ions. The Km for the casein concentration was about 1.62 mg/ml. The activity of CANP was inhibited by one of the thiol protease inhibitors, E-64 analogue (E-64-a). The rate of inhibition was about 50% at an E-64-a concentration of 10(-5)M. This CANP degraded selectively basic protein in myelin proteins and the degradation was inhibited by E-64-a or EGTA. The role of the brain CANP in the process of demyelination was suggested by this study.


Vitamin C consumption is associated with less progression in carotid intima media thickness in elderly men: A 3-year intervention study.
Plant foods may lower the risk of cardiovascular disease. We assessed changes in the intima media thickness (IMT) of the carotid artery and diet in elderly men. Men (n=563) aged 70+/-5 years were randomly assigned to 1 of 4 groups (dietary intervention, omega-3 supplementation, both or neither) using a 2 x 2 factorial design. B-mode ultrasound of the carotid arteries and calculation of dietary intake were performed at baseline and after 3 years. We previously showed that omega-3 supplementation did not influence the IMT, thus the dietary intervention (n=233) and no dietary intervention (n=231) groups were pooled. The dietary intervention group had less progression in the carotid IMT compared with the controls (0.044+/-0.091 mm versus 0.062+/-0.105 mm; P=0.047). This group increased their daily vitamin C intake (P=0.005) and intake of fruit, berries and vegetables (P<or=0.001). Increased intake of vitamin C and of fruit and berries was inversely associated with IMT progression (r=-0.181; P=0.006 and r=-0.125; P=0.056, respectively). Multivariate linear regression analysis showed that increased intakes of vitamin C and of fruit and berries were associated with less IMT progression in the intervention group and in the total study population, after adjustment for consumption of dietary cholesterol, cheese, saturated fat and group assignment. Vitamin C containing foods may protect against the progression of carotid atherosclerosis in elderly men.


Intracoronary versus intravenous streptokinase in acute myocardial infarction.
To assess the relative efficacy of coronary thrombolysis using intracoronary versus intravenous streptokinase, 32 patients with acute myocardial infarction were randomly assigned to receive intracoronary (n = 17) and intravenous streptokinase (n = 15). All patients underwent selective coronary arteriography before and after administration of streptokinase by either route within 4 hours of the onset of symptoms. Intravenous streptokinase was given as 750,000 units over 30 minutes, while a mean dose of 180,000 units was required for thrombolysis in the group having intracoronary delivery. Recanalization occurred in 71.4% (10 of 14) of patients receiving streptokinase, by the intracoronary group in contrast to only 25% of patients (3 of 12) who received the drug intravenously (P less than 0.05). Spontaneous thrombolysis was seen in 17.6% and 20% of the patients in the groups having intracoronary and intravenous delivery, respectively. Bleeding complications were few in both groups. Thus, when baseline coronary arteriography is performed, recanalization with intracoronary streptokinase is more effective in the treatment of acute myocardial infarction than intravenous streptokinase.


Reconstruction of Gustilo type IIIC tibial open fracture caused by shotgun injury using combination Masquelet technique and cross-leg pedicle flap.
The shotgun injury may cause large-scale bone and soft tissue destruction especially when people get shot from a very close range. Here we present a case of Gustilo type IIIC open fractures of the proximal tibia with vascular injury, large bone and soft tissue defect treated with Masquelet technique in combination with cross-leg pedicle flap. A 34-year-old man presented with open proximal tibial fracture of Gustilo type IIIC, AO/OTA (Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association) classification 41-C2.3, caused by a shotgun injury from very close range (2 m). The wound was complicated with anterior tibial artery injury and segmental bone loss. After radical debridement, the fracture was temporarily stabilized with external fixator, followed by double plate fixation with cement spacer filled into the bone defect in accordance with the Masquelet technique. The soft tissue defect was covered with a cross-leg pedicle flap. At 3 months after trauma, the cement spacer was replaced by mixed autologous and synthetic bone graft. The fracture had successfully healed by 12 months after trauma. When the integrity of lower leg vessels is doubtful, the Masquelet technique in combination with cross-leg pedicle flap is an effective and safe alternative treatment for this condition. We recommend to manage Gustilo type IIIC open fractures of the proximal tibia with bone defect with Masquelet technique in combination with cross-leg pedicle flap especially when the free flap technique is relatively contraindicated or trauma surgeon is not a highly-skilled microsurgeon.


Structural studies of the Escherichia coli O-antigen 25.
The structure of the Escherichia coli O-antigen 25 has been investigated using n.m.r. spectroscopy, methylation analysis, and various specific degradations. It is concluded that the O-antigen is composed of pentasaccharide repeating-units having the following structure.