Cartilaginous tissue formation from bone marrow cells using rotating wall vessel (RWV) bioreactor.
This is the first successful report of the rapid regeneration of three-dimensional large and homogeneous cartilaginous tissue from rabbit bone marrow cells without a scaffold using a rotating wall vessel (RWV) bioreactor, which simulates a microgravity environment for cells. Bone marrow cells cultured for 3 weeks in DMEM were resuspended and cultured for 4 weeks in the chondrogenic medium within the vessel. Large cylindrical cartilaginous tissue with dimensions of (1.25 +/- 0.06) x (0.60 +/- 0.08) cm (height x diameter) formed. Their cartilage marker expression was confirmed by mRNA expressions of aggrecan, collagen type I and II, and glycosaminoglycan (GAG)/DNA ratio. Their cartilaginous properties were demonstrated by toluidine blue, safranin-O staining, and polarization.


Protein kinase Cα phosphorylates a novel argininosuccinate synthase site at serine 328 during calcium-dependent stimulation of endothelial nitric-oxide synthase in vascular endothelial cells.
Endothelial nitric-oxide synthase (eNOS) utilizes l-arginine as its principal substrate, converting it to l-citrulline and nitric oxide (NO). l-Citrulline is recycled to l-arginine by two enzymes, argininosuccinate synthase (AS) and argininosuccinate lyase, providing the substrate arginine for eNOS and NO production in endothelial cells. Together, these three enzymes, eNOS, AS, and argininosuccinate lyase, make up the citrulline-NO cycle. Although AS catalyzes the rate-limiting step in NO production, little is known about the regulation of AS in endothelial cells beyond the level of transcription. In this study, we showed that AS Ser-328 phosphorylation was coordinately regulated with eNOS Ser-1179 phosphorylation when bovine aortic endothelial cells were stimulated by either a calcium ionophore or thapsigargin to produce NO. Furthermore, using in vitro kinase assay, kinase inhibition studies, as well as protein kinase Cα (PKCα) knockdown experiments, we demonstrate that the calcium-dependent phosphorylation of AS Ser-328 is mediated by PKCα. Collectively, these findings suggest that phosphorylation of AS at Ser-328 is regulated in accordance with the calcium-dependent regulation of eNOS under conditions that promote NO production and are in keeping with the rate-limiting role of AS in the citrulline-NO cycle of vascular endothelial cells.


Specular Beamforming.
Acoustically hard objects, such as bones, needles, or catheters, are poorly visualized in conventional ultrasound images. These objects behave like acoustic mirrors and reflect sound in specific directions. Soft tissue and diffusive reflectors scatter sound in a broad range of directions. Conventional delay-and-sum beamforming is based on the assumption of a purely scattering domain with relatively weak reflectivity. We present an adaptive beamforming technique that takes into account the physics of specular reflection. Patterns predicted by the law of reflection are detected across the pool of received data and used to enhance the visualization of specular energy. This technique can be applied to any synthetic imaging sequence. Here, it is applied to synthetic transmit aperture imaging. In vitro experiments show a clear improvement in target visibility and an increase of 30 to 60 dB in signal-to-noise ratio.


[General review: classification of urticaria and angioedema].
The authors propose a classification of urticarias and angio-oedemas according to two criteria, physiopathological and etiological. In the first group they identify three subgroups; immunological, non-immunological and idiopathological. In the second group they classify the facts into 12 sub-groups, which are detailed.


Solitary and multiple epidermolytic acanthoma: A demographic and clinical study of 131 cases.
Epidermolytic acanthoma (EA) is a rare, benign acquired cutaneous keratosis displaying epidermolytic hyperkeratosis in more than 50% of its surface. Because of the sparsity of comprehensive studies, little is known on the patient demographics and clinical characteristics of this uncommon entity. We wish to comprehensively characterize the clinical and demographic features of EA and to differentiate it from its mimickers. We carried out a retrospective review of 131 cases of EA, recorded clinical and histopathologic features and performed linear regression of yearly incidence rates to assess for possible under-reporting of this entity. EA affected both genders equally. We found 9.08 cases per 100 000 biopsy specimens per year and linear regression analysis showed significantly decreasing incidence rates. Analysis of the anatomical site distribution of EA lesions showed a more frequent genital location in men (39.1% of cases in men, as compared to 11.3% for women). Contrary to previous studies, lesions were most frequently single (91.7%) and the mean age of presentation was 57.8 years. The presented largest case series to-date indicates that EA is probably an underdiagnosed entity and establishes the demographic and clinical features of EA.


In vitro and in silico studies of the membrane permeability of natural flavonoids from Silybum marianum (L.) Gaertn. and their derivatives.
In recent years the number of natural products used as pharmaceuticals, components of dietary supplements and cosmetics has increased tremendously requiring more extensive evaluation of their pharmacokinetic properties. This study aims at combining in vitro and in silico methods to evaluate the gastrointestinal absorption (GIA) of natural flavonolignans from milk thistle (Silybum marianum (L.) Gaertn.) and their derivatives. A parallel artificial membrane permeability assay (PAMPA) was used to evaluate the transcellular permeability of the plant main components. A dataset of 269 compounds with measured PAMPA values and specialized software tools for calculating molecular descriptors were utilized to develop a quantitative structure-activity relationship (QSAR) model to predict PAMPA permeability. The PAMPA permeabilities of 7 compounds constituting the main components of the milk thistle were measured and their GIA was evaluated. A freely-available and easy to use QSAR model predicting PAMPA permeability from calculated physico-chemical molecular descriptors was derived and validated on an external dataset of 783 compounds with known GIA. The predicted permeability values correlated well with obtained in vitro results. The QSAR model was further applied to predict the GIA of 31 experimentally untested flavonolignans. According to both in vitro and in silico results most flavonolignans are highly permeable in the gastrointestinal tract, which is a prerequisite for sufficient bioavailability and use as lead structures in drug development. The combined in vitro/in silico approach can be used for the preliminary evaluation of GIA and to guide further laboratory experiments on pharmacokinetic characterization of bioactive compounds, including natural products.


Inhibition of fibroblast chemotaxis by superoxide dismutase.
Superoxide radicals are known to be important mediators in chronic inflammatory and fibrotic processes, in which accumulation of fibroblasts is thought to play a major role in the pathogenetic events. The enzyme superoxide dismutase removes these radicals by a catalytic reaction. Chemotactic response of human fibroblasts and fibrosarcoma-derived cells (HT-1080) to fibroblast conditioned medium, fibronectin and platelet-derived growth factor was inhibited in a dose-dependent manner in the presence of superoxide dismutase, while random migration, cell proliferation, cell viability and synthesis of collagen and non-collagenous proteins was not altered. In contrast, phorbol myristate acetate, an inducer of superoxide generation, stimulated the chemotactic movement of fibroblasts to the attractants. Evidence for the formation of superoxide is provided by the reduction of tetrazolium salt by activated fibroblasts which could be inhibited by superoxide dismutase. Thus, it is concluded that superoxide in small amounts is involved in the mechanism of fibroblast chemotaxis. Superoxide dismutase may, therefore, reduce fibroblast migration into sites of injury or inflammation.


Dosimetric evaluation of the interplay effect in respiratory-gated RapidArc radiation therapy.
Volumetric modulated arc therapy (VMAT) with gating capability has had increasing adoption in many clinics in the United States. In this new technique, dose rate, gantry rotation speed, and the leaf motion speed of multileaf collimators (MLCs) are modulated dynamically during gated beam delivery to achieve highly conformal dose coverage of the target and normal tissue sparing. Compared with the traditional gated intensity-modulated radiation therapy technique, this complicated beam delivery technique may result in larger dose errors due to the intrafraction tumor motion. The purpose of this work is to evaluate the dosimetric influence of the interplay effect for the respiration-gated VMAT technique (RapidArc, Varian Medical Systems, Palo Alto, CA). Our work consisted of two parts: (1) Investigate the interplay effect for different target residual errors during gated RapidArc delivery using a one-dimensional moving phantom capable of producing stable sinusoidal movement; (2) Evaluate the dosimetric influence in ten clinical patients' treatment plans using a moving phantom driven with a patient-specific respiratory curve. For the first part of this study, four plans were created with a spherical target for varying residual motion of 0.25, 0.5, 0.75, and 1.0 cm. Appropriate gating windows were applied for each. The dosimetric effect was evaluated using EDR2 film by comparing the gated delivery with static delivery. For the second part of the project, ten gated lung stereotactic body radiotherapy cases were selected and reoptimized to be delivered by the gated RapidArc technique. These plans were delivered to a phantom, and again the gated treatments were compared to static deliveries by the same methods. For regular sinusoidal motion, the dose delivered to the target was not substantially affected by the gating windows when evaluated with the gamma statistics, suggesting the interplay effect has a small role in respiratory-gated RapidArc therapy. Varied results were seen when gated therapy was performed on the patient plans that could only be attributed to differences in patient respiratory patterns. Patients whose plans had the largest percentage of pixels failing the gamma statistics exhibited irregular breathing patterns including substantial interpatient variation in depth of respiration. The interplay effect has a limited impact on gated RapidArc therapy when evaluated with a linear phantom. Variations in patient breathing patterns, however, are of much greater clinical significance. Caution must be taken when evaluating patients' respiratory efforts for gated arc therapy.


Wearable Device-Based Gait Recognition Using Angle Embedded Gait Dynamic Images and a Convolutional Neural Network.
The widespread installation of inertial sensors in smartphones and other wearable devices provides a valuable opportunity to identify people by analyzing their gait patterns, for either cooperative or non-cooperative circumstances. However, it is still a challenging task to reliably extract discriminative features for gait recognition with noisy and complex data sequences collected from casually worn wearable devices like smartphones. To cope with this problem, we propose a novel image-based gait recognition approach using the Convolutional Neural Network (CNN) without the need to manually extract discriminative features. The CNN's input image, which is encoded straightforwardly from the inertial sensor data sequences, is called Angle Embedded Gait Dynamic Image (AE-GDI). AE-GDI is a new two-dimensional representation of gait dynamics, which is invariant to rotation and translation. The performance of the proposed approach in gait authentication and gait labeling is evaluated using two datasets: (1) the McGill University dataset, which is collected under realistic conditions; and (2) the Osaka University dataset with the largest number of subjects. Experimental results show that the proposed approach achieves competitive recognition accuracy over existing approaches and provides an effective parametric solution for identification among a large number of subjects by gait patterns.


Context matters for preschool discipline: Effects of distance learning and pandemic fears.
The COVID-19 pandemic transformed the context and delivery of early childhood education, yet little is known about its impact on exclusionary discipline (e.g., suspension, expulsion), which nationally representative evidence has shown disproportionately impacts Black boys. Using one experiment, we test how preschool providers respond to three hypothetical vignettes about a Black boy's behaviors. Participants (N = 60) were randomly assigned to read vignettes set in either distance learning or in-person classroom contexts. Then, participants completed measures about discipline and COVID-19. Results indicated there was an interaction between context and the sequence of vignettes on providers' troubled feelings and endorsements of discipline. Providers showed heightened troubled feelings and endorsements of discipline severity in the distance learning context, as compared to an in-person context, as vignettes progressed. Additionally, the more providers feared COVID-19, the more they felt troubled over the course of the vignettes across conditions. Practitioners can use this research to inform consultative interventions that mitigate discipline by directly addressing providers' pandemic fears and classroom contexts. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


[Cholesteatoma of the external auditory meatus].
This article was designed to present a concise overview of the literature concerning cholesteatoma of the external auditory meatus and to report the original clinical observation of this condition with special reference to the necessity of its early diagnostics and surgical treatment with the use of the combination of simultaneous sanation and reconstruction.


Epigenetic-sensitive liquid biomarkers and personalised therapy in advanced heart failure: a focus on cell-free DNA and microRNAs.
Dilated cardiomyopathy (DCM) represents a common genetic cause of mechanical and/or electrical dysfunction leading to heart failure (HF) onset for which truncating variants in titin (TTN) gene result in the most frequent mutations. Moreover, myocyte and endothelial cell apoptosis is a key endophenotype underlying cardiac remodelling. Therefore, a deeper knowledge about molecular networks leading to acute injury and apoptosis may reveal novel circulating biomarkers useful to better discriminate HF phenotypes, patients at risk of heart transplant as well as graft reject in order to improve personalised therapy. Remarkably, increased plasma levels of cell-free DNA (cfDNA) may reflect the extent of cellular damage, whereas circulating mitochondrial DNA (mtDNA) may be a promising biomarker of poor prognosis in patients with HF. Furthermore, some panels of circulating miRNAs may improve the stratification of natural history of disease. For example, a combination of miR-558, miR-122* and miR-520d-5p, as well as miR-125a-5p, miR-550a-5p, miR-638 and miR-190a, may aid to discriminate different phenotypes of HF ranging from preserved to reduced ejection fraction. We give update on the most relevant genetic determinants involved in DCM and discuss the putative role of non-invasive biomarkers to overcome current limitations of the reductionist approach in HF management.


The effect of titanium stabilization rods on spinal cord radiation dose.
The purpose of this study was to investigate the dosimetric effect of a titanium-rod spinal stabilization system on surrounding tissue, especially the spinal cord. Ion chamber dosimetry was performed for 6- and 18-MV photon beams in a water phantom containing a titanium-rod spinal stabilization system. Isodose curves were obtained in the phantom with and without rods. To assess the ability of a treatment planning system to reproduce the effects of the stabilization system on the radiation dose delivered to surrounding tissue, dose distributions were calculated after appropriate modifications were made in the computed tomography number-to-density conversion table to account for the increased density of the titanium rods. The resultant heterogeneity-corrected plans were compared with uncorrected plans. At a 7-cm depth in the water phantom, corresponding to the depth of the spinal cord, the beam was attenuated by 4% under the rods alone and by 13% rods under the rods with screws for the 6-MV photon beam as compared with curves generated in the absence of rods. The beam was attenuated by 3% and 11%, respectively, for the 18-MV beam. Using anteroposterior (18-MV) and posteroanterior (6-MV) photon beams, with and without heterogeneity correction for the rods, the corrected isodose plan showed an approximately 2% beam attenuation 4 cm anterior to the rods as compared with the uncorrected plan. No significant difference in the spinal cord dose was observed between the 2 plans, however. The titanium-rod spinal stabilization system tested in this study caused a decrease in the dose delivered distal to the rods but did not significantly affect the dose delivered to the spinal cord.


Origin of surface trap states in CdS quantum dots: relationship between size dependent photoluminescence and sulfur vacancy trap states.
Monodisperse cadmium sulphide (CdS) quantum dots (QDs) with a tunable size from 1.4 to 4.3 nm were synthesized by a non-injection method, and their surface states were characterized by photoluminescence spectroscopy and X-ray Photoelectron Spectroscopy (XPS). The steady state photoluminescence study identified that the proportion of the trap state emission increased with the QD size decrease, while from the photoluminescence decay study, it appeared that the trap state emission results from the emission via a surface deep trap state. The XPS measurements revealed the existence of surface Cd with sulfur vacancy sites which act as electron trap sites, and the population of these sites increases with the QD size decrease. These results are consistent to conclude that the trap state emission mainly originates from the surface deep trapped electrons at the surface Cd with sulfur vacancy sites.


Effect of interparticulate interaction on release kinetics of microsphere ensembles.
The release kinetics of microsphere ensembles is complicated by the mutual influence of the microspheres which are entrapped in small compartments such as body cavities. This work focused on the effect of interparticulate interaction on the release kinetics of microsphere ensembles with limited spreading. Experiments and finite element modeling were conducted to investigate diffusional drug release from a single sphere, a monolayer, and multiple layers of microspheres. Poly(methyl methacrylate-co-methacrylic acid) (P(MMA/MAA)) microspheres and azidothymidine (AZT) were used in the experiments. The order of the release rate of AZT from various microsphere populations was observed to be single sphere > monolayer > multiple layers. This evidenced the importance of interparticulate interaction. The finite element simulations elucidated the influence of various factors on the release kinetics of microsphere ensembles including the separation distance, location of the spheres, and the drug accumulation in the medium. Calibration of overall release kinetics for the neighboring effect was proposed on the basis of the spreading factor. Overall release profiles of microsphere ensembles were predicted using the release profiles of individual microspheres at various locations.


Results of preprocedure and postprocedure toe cultures in orthopaedic surgery.
This study was to determine whether there is any benefit to wrapping the toes sterilely during orthopaedic procedures not involving the foot but performed on the lower extremity. The group studied consisted of 12 patients who had an orthopaedic procedure performed in which the foot and toes were included in the surgical prep, but not involved in the surgical procedure. Nine of the 12 patients (75%) had positive results from preprocedural aerobic cultures and two of the 12 (16.6%) had positive results from preprocedural fungal cultures. Recolonization of the bacteria between the toes was also demonstrated. Sterile draping of the toes would minimize the risk of infection and also protect against bacteria that recolonize during the procedure.


Action of GABA-B antagonist on cortical epileptic afterdischarges in rats is similar to that of GABA-A antagonist.
Threshold intensities for epileptic phenomena induced by cortical stimulation were used for comparison of the action of GABA-B and GABA-A antagonists in rats with implanted electrodes. Both CGP 35348 (200 mg/kg i.p.) and bicuculline (4 mg/kg i.p.) significantly decreased thresholds for spike-and-wave afterdischarges and their motor counterpart (clonic seizures) whilst transition into the second, limbic type of afterdischarge as well as threshold for movements directly bound to stimulation remained uninfluenced by either drug.


Altered DNA methylation is associated with docetaxel resistance in human breast cancer cells.
Docetaxel is an effective chemotherapy drug to treat breast cancer but the underlying molecular mechanisms of drug resistance are not fully understood. DNA methylation is an epigenetic event, involved in the control of gene expression, which is known to play an important role in cancer and chemotherapy drug resistance. To investigate the role of DNA methylation in docetaxel resistance in breast cancer we used two human breast cancer cell lines (MCF-7 and MDA-MB-231) that were made resistant to docetaxel. Docetaxel-resistant sub-lines were treated with different concentrations of decitabine. Global methylation and DNA methyltransferase (DNMT) activity was measured using an ELISA-based assay. Quantitative real-time PCR was used to study DNMT gene expression. Cell viability was studied by MTT assay. Global methylation was increased in MCF-7 but not significantly changed in MDA-MB-231 docetaxel-resistant cells. Decreased DNMT activity and decreased DNMT1 and DNMT3b mRNA expression was associated with docetaxel resistance in both cell lines. To investigate how the components of the DNA methylation machinery may contribute towards docetaxel resistance, decitabine (5-aza-2'-deoxycytidine), an inhibitor of DNA methylation, was used. Decitabine treatment decreased global methylation, DNMT activity and DNMT1, DNMT3a and DNMT3b mRNA expression in MDA-MB-231 docetaxel-resistant cells. In contrast, decitabine-treated MCF-7 docetaxel-resistant cells showed increased DNMT1, DNMT3a and DNMT3b mRNA expression indicating a cell line specific effect of decitabine. Decitabine treatment increased resistance in MCF-7 docetaxel-resistant cells and in the parental MCF-7 and MDA-MB231 docetaxel-sensitive cell lines, however, it did not alter response to docetaxel in MDA-MB-231 docetaxel-resistant cells. This study demonstrates that changes in the DNA methylation machinery are associated with resistance to docetaxel in breast cancer cells. The use of epigenetic therapies, as a strategy to overcome drug resistance, needs to be investigated more fully to determine their effectiveness in different cancers and for different chemotherapy drugs.


Provider Workforce Assessment in a Rural Hepatitis C Epidemic: Implications for Scale-up of Antiviral Therapy.
New recommendations for birth cohort screening for hepatitis C virus (HCV) infection and the development of new, highly effective antiviral medications are expected to increase the demand for HCV treatment. In the past, antiviral therapy for HCV was almost exclusively prescribed by specialists in the field of gastroenterology and infectious diseases, meaning that people living in rural areas that are underserved by specialists may have poor access to treatment. We investigated the number and geographic distribution of medical providers who actively prescribed direct acting antiviral drugs for hepatitis C in Wisconsin during 2012. Using public health surveillance data and a state-wide prescription drug database, we found that there was 1 treatment provider for every 340 residents known to be living with HCV. However, 51 of 72 Wisconsin counties had no providers who provided HCV treatment in 2012.Scaling up antiviral treatment to address the epidemic of hepatitis C efficiently and equitably will require strategies to increase the number of treatment providers in rural communities. Providing education, training, and support to the primary care workforce serving rural communities should be considered a potentially effective and efficient approach to preventing future HCV-related illness.


Distinct outcomes of Trypanosoma cruzi infection in hamsters are related to myocardial parasitism, cytokine/chemokine gene expression, and protein expression profile.
Trypanosoma cruzi-infected outbred hamsters reproduce the range of different outcomes of Chagas disease noted in humans. We tested whether myocarditis, its mediators, and myocardial protein expression are related to the severity of the acute phase of T. cruzi infection in the hamster model. Myocardium left ventricles (LVs) obtained from Syrian hamsters infected with T. cruzi were collected 21 days after infection. Myocarditis and the T. cruzi nest/antigen area were analyzed by histological and morphometric analysis. Cytokine and chemokine messenger RNA (mRNA) expression was analyzed using real-time reverse-transcriptase polymerase chain reaction. Differentially expressed proteins were identified by 2-dimensional electrophoresis, followed by mass spectrometry. While in the acute phase of infection, 50% of animals displayed weight loss and signs of acute-phase infection (hereafter referred to as "acute-phase signs" [APS]) (e.g., lethargy, vomiting, and diarrhea). Both the T. cruzi nest/antigen area and the expression of interferon-gamma, tumor necrosis factor-alpha, interleukin-10, and CCL3 mRNA were significantly increased in the LVs of animals with APS, compared with the LVs of animals without APS. Animals with APS, those without APS, and uninfected animals demonstrated distinct myocardial expression of contractile, stress response, and metabolism proteins. The distinct outcomes of acute T. cruzi infection in Syrian hamsters are related to cardiac parasitism, cytokine expression, and changes in the expression of structural/contractile and stress response proteins that may be associated with alterations in the cardiomyocyte cytoskeleton.


Mutation of Tyr137 of the universal Escherichia coli fimbrial adhesin FimH relaxes the tyrosine gate prior to mannose binding.
The most prevalent diseases manifested by Escherichia coli are acute and recurrent bladder infections and chronic inflammatory bowel diseases such as Crohn's disease. E. coli clinical isolates express the FimH adhesin, which consists of a mannose-specific lectin domain connected via a pilin domain to the tip of type 1 pili. Although the isolated FimH lectin domain has affinities in the nanomolar range for all high-mannosidic glycans, differentiation between these glycans is based on their capacity to form predominantly hydrophobic interactions within the tyrosine gate at the entrance to the binding pocket. In this study, novel crystal structures of tyrosine-gate mutants of FimH, ligand-free or in complex with heptyl α-d-O-mannopyranoside or 4-biphenyl α-d-O-mannopyranoside, are combined with quantum-mechanical calculations and molecular-dynamics simulations. In the Y48A FimH crystal structure, a large increase in the dynamics of the alkyl chain of heptyl α-d-O-mannopyranoside attempts to compensate for the absence of the aromatic ring; however, the highly energetic and stringent mannose-binding pocket of wild-type FimH is largely maintained. The Y137A mutation, on the other hand, is the most detrimental to FimH affinity and specificity: (i) in the absence of ligand the FimH C-terminal residue Thr158 intrudes into the mannose-binding pocket and (ii) ethylenediaminetetraacetic acid interacts strongly with Glu50, Thr53 and Asn136, in spite of multiple dialysis and purification steps. Upon mutation, pre-ligand-binding relaxation of the backbone dihedral angles at position 137 in the tyrosine gate and their coupling to Tyr48 via the interiorly located Ile52 form the basis of the loss of affinity of the FimH adhesin in the Y137A mutant.


[Immune monitoring of the cancer patient: suppressor cells and NK cells].
Immune monitoring in cancer patients consists mainly in the analysis of the immune deficiency, the search for immune modulators and the examination of antitumor reactions. Suppressor cells have been demonstrated in Hodgkin's disease and lung carcinoma. Azimexon, a synthetic immune adjuvant has shown in anergic cancer patients powerfull restorative properties. Spontaneous cell mediated cytoxicity can been enhanced by interferon of lymphokines injections.


A liquid-crystalline perylene tetracarboxylic bisimide derivative bearing a triethylene oxide chain and complexation of the derivative with Li cations.
A liquid-crystalline (LC) perylene tetracarboxylic bisimide (PTCBI) derivative bearing a triethylene oxide chain as well as two pentamethyldisiloxane chains was synthesized. This compound exhibits an ordered lamellar phase at room temperature, and the LC phase is retained when the sample is cooled to -100 °C. Due to the presence of extended π-conjugated perylene rings, efficient electron transport occurs in the lamellar phase and the electron mobility exceeds 1 × 10(-3) cm(2) V(-1) s(-1) at room temperature. Moreover, this PTCBI derivative can form a complex with lithium triflate because of the polar triethylene oxide chain. Lithium triflate can be mixed with it up to 3 mol%. Up to this concentration, the lamellar LC structure and the electron transport properties are not perturbed by the presence of the ionic species.


Sulfinpyrazone and postoperative deep vein thrombosis.
Small doses of subcutaneous heparin and infusions of dextran both reduce the incidence of fatal pulmonary embolism after elective general surgery. But both methods have disadvantages. Therefore, the protection against deep vein thrombosis afforded by sulfinpyrazone, a drug which can be taken by mouth as well as by injection, was assessed in a prospective study of 119 patients undergoing elective general or urological surgery. The prophylactic administration of sulfinpyrazone was compared with the effects of small doses of sodium heparin and infusions of dextran-70. The 125I-fibrinogen test was carried out in all patients during their hospitalization. Deep vein thrombosis was diagnosed in 13 of 30 patients (43%) who received sulfinpyrazone, in 9 of 29 (31%) receiving dextran-70 and in 2 of 22 (9%) having subcutaneous heparin. The difference between the sulfinpyrazone and heparin groups was statistically significant (p less than 0.01). Sulfinpyrazone in the dose used in this trial was not effective in reducing the incidence of deep vein thrombosis during elective general surgery.


Pharmacodynamic modeling of thrombopoietin, platelet, and megakaryocyte dynamics in patients with acute myeloid leukemia undergoing dose intensive chemotherapy.
A proposed model of thrombopoietin (TPO) regulation is that of a constitutive production of TPO with circulating levels being predominately regulated by changes in platelet and megackaryocyte mass. Using a pharmacodynamic (PD) approach, the authors examined the validity of this model for patients with acute myeloid leukemia (AML) undergoing dose-intensive postinduction chemotherapy (HDT). TPO and platelet values were assayed weekly in AML patients undergoing HDT. A parsimonious dynamic model was then applied to these experimental data. The results (1) support the proposed model of TPO regulation, (2) model and quantify the effects of HDT on the megakaryocyte compartment, (3) characterize variables not amenable to direct measurement, and (4) have clinical utility as this model predicted that TPO given after HDT would not have a significant effect on platelet recovery, a finding borne out in clinical trials. This model provides information relevant to the interpretation of clinical trials of hematopoietic growth factors.


Bilateral photon deficient area along lateral abdominal wall in a Tc-99m DTPA renogram. A sign of massive ascites.
A patient with congestive heart failure and hepatic and renal dysfunction underwent Tc-99m DTPA renal scintigraphic studies in which persistent cardiac blood pool activity, hepatic arterialization, and a longitudinal photon deficient area in each side of the abdominal wall were observed. The increase in hepatic artery inflow was believed to be due to a decrease in portal inflow of the liver. The elevation of portal pressure secondary to heart failure is attributable to the decrease in portal inflow of the liver; this phenomenon could account for the hepatic arterialization. Progressive renal dysfunction with high body background resulted in demonstrable ascites as photon deficient areas. Scintigraphic findings of hepatic arterialization plus an abdominal photon deficient area reflect severe heart failure and renal dysfunction.


De Novo Deep Transcriptome Analysis of Medicinal Plants for Gene Discovery in Biosynthesis of Plant Natural Products.
Study on transcriptome, the entire pool of transcripts in an organism or single cells at certain physiological or pathological stage, is indispensable in unraveling the connection and regulation between DNA and protein. Before the advent of deep sequencing, microarray was the main approach to handle transcripts. Despite obvious shortcomings, including limited dynamic range and difficulties to compare the results from distinct experiments, microarray was widely applied. During the past decade, next-generation sequencing (NGS) has revolutionized our understanding of genomics in a fast, high-throughput, cost-effective, and tractable manner. By adopting NGS, efficiency and fruitful outcomes concerning the efforts to elucidate genes responsible for producing active compounds in medicinal plants were profoundly enhanced. The whole process involves steps, from the plant material sampling, to cDNA library preparation, to deep sequencing, and then bioinformatics takes over to assemble enormous-yet fragmentary-data from which to comb and extract information. The unprecedentedly rapid development of such technologies provides so many choices to facilitate the task, which can cause confusion when choosing the suitable methodology for specific purposes. Here, we review the general approaches for deep transcriptome analysis and then focus on their application in discovering biosynthetic pathways of medicinal plants that produce important secondary metabolites.


Preoperative imatinib for patients with primary unresectable or metastatic/recurrent gastrointestinal stromal tumor.
Despite its rising popularity, reports on the use of preoperative imatinib mesylate (IM) in patients with advanced gastrointestinal stromal tumor (GIST) are limited. This study aims to explore the clinical efficacy of preoperative IM in patients with primarily unresectable or metastatic/recurrent GIST. Between September 2009 and February 2014, patients with primarily unresectable or metastatic/recurrent GIST treated by a single medical team were recruited and considered for preoperative IM therapy. Re-examination was conducted regularly and abdominal enhanced CT data, blood biochemistry and responses to IM were recorded. A total of 18 patients were enrolled, including 13 with a primary tumor (7 stomach, 3 small bowel, 2 rectal and 1 pelvic tumor) and 5 with recurrent or metastatic GIST (2 with liver metastasis, 2 with anastomotic recurrence and 1 with pelvic GIST). The median follow-up time was 9.5 months (range of 3-63). The median tumor sizes before and after initiation of IM treatment were 9.1 cm and 6.0 cm (p=0.003) based on the CT findings, respectively. All patients showed a decrease in tumor burden and the median tumor size reduction was 35%. Sixteen of the 18 patients showed a partial response to IM and two possessed stable disease. Nine of the 18 patients (50%) underwent surgical resection of primary or metastatic/recurrent tumors, with a median of 7 months of IM therapy. One case each of multivisceral resection and tumor recurrence were noted. IM as a preoperative therapy is feasible and safe for unresectable or metastatic/recurrent GIST that can effectively decrease tumor size, facilitating resection.


Identifying the dataset to define the optimal timing of histopathological examination for central nervous system toxicity in MPTP-induced Parkinson's disease monkey model.
Determining the optimal timing for histopathological examination following exposure to a test article is crucial for assessing neurotoxicity. However, no study has focused on identifying an ideal dataset to define the optimal timing for histopathological examination of central nervous system (CNS) toxicity in monkeys. Therefore, this study aimed to define a predictive endpoint that would guide us in selecting the optimal timing for histopathological examination of CNS toxicity in monkeys. Four cynomolgus monkeys were administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intravenously at a dosage of 0.6 mg/kg twice at 1-week intervals. Necropsies were performed 1 week after the final dose. The Parkinsonian rating (PR) score and temporal changes in neurofilament light chain and glial fibrillary acidic protein concentrations in the cerebrospinal fluid (CSF) and serum were evaluated and compared with the histopathological findings in the brain. The PR score of all animals administered MPTP increased from days 10 to 11, with some degree of individual variability. Microscopically, all animals showed axonal swelling and vacuolation, with or without microgliosis in the nigrostriatal bundle. However, substantial neurodegenerative findings were observed only in animals with high PR scores at necropsy. A slight increase in CSF biomarker levels at necropsy was also observed in animals with high PR scores. However, their correlation with microscopic findings in these animals was unclear. These data suggest that comprehensive clinical observations, such as PR score alone or combined with other CSF biomarkers, could be further evaluated as potential indicators for triggering anatomic CNS evaluations in monkeys following toxic insults.


Evaluation of immunotoxicity induced by propoxure in C57Bl/6 mice.
Insecticides are important candidates for immunotoxicology tests in order to assess the 'No Observable Adverse Effect Level' (NOAEL). Propoxure (PPX), as a carbamate household insecticide, has been used for several decades around the world in agriculture. However, there has been no clear investigation on its immunotoxic potentials. In this study, as Tier I of immunotoxicological screening tests, we examined the effects of subacute exposure to intraperitoneally (i.p.) administered PPX, at doses of 10, 2, and 0.2 mg/kg, on C57Bl/6 female mice. After 28 days administration of PPX, the treated animals were sacrificed and peripheral blood samples were collected. Then spleen (SP), thymus (TM), and bone marrow were collected and weighed. Functional tests including SRBC-hemagglutination (HA), plaque-forming colony assay (PFC), and delayed type hypersensitivity (DTH) response to SRBCs were performed. Furthermore, spleen T-cell phenotype (CD4/CD8) was also determined. Results showed that high doses of PPX could not only produce histopathological changes in TM and SP but also suppress humoral response to antigen (SRBCs). PPX at medium doses (2 mg/kg) did not show histopathological changes in TM or SP but increased the humoral response to SRBCs, as identified by HA and PFC tests. PPX at low doses (0.2 mg/kg) did not produce any significant changes in humoral (PFC and HA) or cellular responses (DTH) of the immune system. It seems that PPX has no adverse effects on mice immune system at low doses of 0.2 mg/kg/day, which is 10 times the PPX allowed daily intake (ADI) limit.


Using Lagrangian coherent structures to analyze fluid mixing by cilia.
Motivated by the desire to understand the fluid flow within the airway surface liquid of the lung, we consider the flow generated by a computational model of a motile, internally actuated cilium. The cilium, along with a mucus layer modeled by linear elastic elements, is coupled to a viscous, incompressible fluid. The evolution of this coupled system is captured using an immersed boundary method. The Eulerian velocity field computed on a grid is used to compute finite-time Lyapunov exponent fields, whose maximal ridges identify Lagrangian coherent structures (LCSs). The computed LCS uncovers a barrier that separates a recirculation region of fluid that remains near the beating cilium from fluid that is advected downstream. Moreover, periodic stretching and folding of this region gives rise to complex mixing. Flow structures around a cilium propelling a mucus layer are compared to flow structures around a cilium with no mucus load.


Free radical injury in human renal allograft rejection.
Plasma and renal tissue levels of lipid peroxide and plasma vitamin E were estimated as measures of free radical injury in five renal allograft recipients with untreated and four with unsuccessfully treated acute cellular rejection and compared with 11 control patients with minimal change disease. Plasma lipid peroxide was significantly higher in patients studied before antirejection therapy (13.2 +/- 3.5 nmol/ml; P < 0.01) as well as in those after unsuccessful antirejection treatment (11.7 +/- 0.7 nmol/ml; P < 0.01), compared to controls (5.7 +/- 2.8 nmol/ml). Levels of plasma vitamin E and renal tissue lipid peroxide were similar in both groups, however the latter was significantly raised in patients evaluated prior to antirejection therapy than in those after unsuccessful antirejection therapy (5.1 +/- 1.7 and 3.0 +/- 0.8 nmol/mg protein; P < 0.05). These findings suggest possible free radical mediated injury during renal allograft rejection.


Rapid Determination of Interfacial Tensions in Nanopores: Experimental Nanofluidics and Theoretical Models.
A rapid and accurate determination of interfacial tensions (IFTs) in nanopores is scientifically and practically significant, while most existing experimental measurements are restricted to the micrometer scale and theoretical calculations are relatively limited. In this study, six series of the IFT measurement tests for the binary CO2-C10, C1-C10, and N2-C10 mixtures are conducted at temperatures ( T) of 25.0 and 53.0 °C in a self-manufactured nanofluidic system. Moreover, a nanoscale-extended equation-of-state model considering the effects of the confinement, intermolecular interactions, and disjoining pressure and a semianalytical correlation are proposed to calculate the IFTs of the three mixtures in bulk phase and nanopores. Third, a new Tolman length formulation is developed for the IFT corrections in nanopores. Overall, the calculated IFTs from the two theoretical methods agree well with the measured results for most cases in nanopores. On the other hand, effects of the pore scale, temperature, pressure, and fluid composition on the IFTs of the three mixtures are effectively validated and specifically investigated. One suggestion comes from this work that the two theoretical methods for calculating the IFTs are better to be applied concurrently to minimize errors. Another important future work is to include more pore surface parameter (e.g., wettability) into the theoretical model.


Hypoplastic Left Heart Syndrome: An Overview for Primary Care Providers.
Hypoplastic left heart syndrome is one of the most complex congenital heart diseases and requires several cardiac surgeries for survival. The diagnosis is usually established prenatally or shortly after birth. Each stage of surgery poses a unique hemodynamic situation that requires deeper understanding to manage common pediatric problems such as dehydration and respiratory infections. Careful multidisciplinary involvement in the care of these complex patients is improving their outcome; however, morbidity and mortality are still substantial. In this review, we focus on the hemodynamic aspects of various surgical stages that a primary care provider should know to manage these challenging patients.


An Accessible Organotypic Microvessel Model Using iPSC-Derived Endothelium.
While organotypic approaches promise increased relevance through the inclusion of increased complexity (e.g., 3D extracellular microenvironment, structure/function relationships, presence of multiple cell types), cell source is often overlooked. Induced pluripotent stem cell (iPSC)-derived cells are potentially more physiologically relevant than cell lines, while also being less variable than primary cells, and recent advances have made them commercially available at costs similar to cell lines. Here, the use of induced pluripotent stem cell-derived endothelium for the generation of a functional microvessel model is demonstrated. High precision structural and microenvironmental control afforded by the design approach synergizes with the advantages of iPSC to produce microvessels for modeling endothelial biology in vitro. iPSC microvessels show endothelial characteristics, exhibit barrier function, secrete angiogenic and inflammatory mediators, and respond to changes in the extracellular microenvironment by altering vessel phenotype. Importantly, when deployed in the investigation of neutrophils during innate immune recruitment, the presence of the iPSC endothelial vessel facilitates neutrophil extravasation and migration toward a chemotactic source. Relevant cell sources, such as iPSC, combine with organotypic models to open the way for improved and increasingly accessible in vitro tissue, disease, and patient-specific models.


[The double red cross: simple decoration or deliberate emblem?].
In general, the origins of the double transverse red cross (Croix à double traverse), such as that of Lorraine, is less evident than that of the "Double Red Cross" ("Double Croix-Rouge"), as exemplified by the international emblem of the battle against tuberculosis. The importance of the proportions of the latter is emphasised.


The Taste of Emotion: Metaphoric Association Between Taste Words and Emotion/Emotion-Laden Words.
According to the Conceptual Metaphor Theory, abstract concepts can be metaphorically associated with more concrete, physically embodied concepts, such as gustatory experience. Studies on taste-emotion metaphoric association reported that people associate love with sweet, jealousy with sour and bitter, and sadness with bitter. However, few studies have systematically examined the metaphoric association between taste and words referred to emotion (e.g., "sad") or emotion-laden concepts (e.g., "funeral"). In the current four studies (total N = 357), we examined this metaphoric association by having participants come up with a taste word when reading an emotion and emotion-laden word (Study 1-explicit association of taste words-to-emotion/emotion-laden words), come up with an emotion word when reading taste words (Study 2-explicit association of emotion words-to-taste words), rate the association between taste words and basic or non-basic emotion words (Study 3), and rate the association between taste words and a more expanded pool of emotion/emotion-laden words (Study 4). Results showed that sweet was mostly associated with positive emotion and emotion-laden words, whereas bitter, followed by sour and spicy, was mostly associated with negative emotion and emotion-laden words. The bidirectionality of taste-emotion metaphoric association was supported by our dataset. The implications of these findings on the Conceptual Metaphor Theory and embodied cognition are discussed.


Erlotinib versus docetaxel as second-line treatment of patients with advanced non-small-cell lung cancer and wild-type EGFR tumours (TAILOR): a randomised controlled trial.
Erlotinib is registered for treatment of all patients with advanced non-small-cell lung cancer (NSCLC). However, its efficacy for treatment of patients whose tumours are EGFR wild-type-which includes most patients-is still contentious. We assessed the efficacy of erlotinib compared with a standard second-line chemotherapy in such patients. We did this randomised controlled trial in 52 Italian hospitals. We enrolled patients who had metastatic NSCLC, had had platinum-based chemotherapy, and had wild-type EGFR as assessed by direct sequencing. Patients were randomly assigned centrally (1:1) to receive either erlotinib orally 150 mg/day or docetaxel intravenously 75 mg/m(2) every 21 days or 35 mg/m(2) on days 1, 8, and 15, every 28 days. Randomisation was stratified by centre, stage, type of first-line chemotherapy, and performance status. Patients and investigators who gave treatments or assessed outcomes were not masked to treatment allocation, investigators who analysed results were. The primary endpoint was overall survival in the intention-to-treat population. The study is registered at ClinicalTrials.gov, number NCT00637910. We screened 702 patients, of whom we genotyped 540. 222 patients were enrolled (110 assigned to docetaxel vs 112 assigned to erlotinib). Median overall survival was 8·2 months (95% CI 5·8-10·9) with docetaxel versus 5·4 months (4·5-6·8) with erlotinib (adjusted hazard ratio [HR] 0·73, 95% CI 0·53-1·00; p=0·05). Progression-free survival was significantly better with docetaxel than with erlotinib: median progression-free survival was 2·9 months (95% CI 2·4-3·8) with docetaxel versus 2·4 months (2·1-2·6) with erlotinib (adjusted HR 0·71, 95% CI 0·53-0·95; p=0·02). The most common grade 3-4 toxic effects were: low absolute neutrophil count (21 [20%] of 104 in the docetaxel group vs none of 107 in the erlotinib group), skin toxic effects (none vs 15 [14%]), and asthenia (ten [10%] vs six [6%]). Our results show that chemotherapy is more effective than erlotinib for second-line treatment for previously treated patients with NSCLC who have wild-type EGFR tumours.


Post-Covid-19 Airway Stenosis: Tracheal Resection-Anastomosis Using The Tritube® Ventilation.
We present a video of a tracheal resection and anastomosis performed on a patient affected by A-shaped tracheal stenosis. The condition was a consequence of a percutaneous tracheostomy following a Sars-Cov2 infection. Airways management during the surgery was obtained with the Tritube®, an innovative device with a very small lumen that combines stable lung parameters and good visualization of surgical field. Laryngoscope, 2023.


Treatment of radiation-induced acute intestinal injury with bone marrow-derived mesenchymal stem cells.
The aim of the present study was to investigate the ability of bone marrow-derived mesenchymal stem cells (BMSCs) to repair radiation-induced acute intestinal injury, and to elucidate the underlying repair mechanism. Male Sprague-Dawley rats were subjected to whole abdominal irradiation using a single medical linear accelerator (12 Gy) and randomly assigned to two groups. Rats in the BMSC-treated group were injected with 1 ml BMSC suspension (2×106 cells/ml) via the tail vein, while the control group rats were injected with normal saline. BMSCs were identified by detecting the expression of CD29, CD90, CD34 and CD45 using flow cytometry. The expression of the cytokines stromal cell-derived factor 1 (SDF-1), prostaglandin E2 (PGE2) and interleukin (IL)-2 was detected using immunohistochemical techniques. Plasma citrulline concentrations were evaluated using an ELISA kit. Rat general conditions, including body weight, and changes in cellular morphology were also recorded. The results suggested that BMSCs exerted a protective effect on radiation-induced acute intestinal injury in rats. The histological damage was rapidly repaired in the BMSC-treated group. In addition, the BMSC-treated group showed significantly reduced radiation injury scores (P<0.01), mildly reduced body weight and plasma citrulline levels, significantly more rapid recovery (P<0.01), significantly reduced expression of the cytokines PGE2 and IL-2 (P<0.05) and significantly increased SDF-1 expression (P<0.01) compared with the control group. In summary, the present results indicate that BMSCs are able to effectively reduce inflammation and promote repair of the structure and function of intestinal tissues damaged by radiation exposure, suggesting that they may provide a promising therapeutic agent.


Selective BET inhibitor RVX-208 ameliorates periodontal inflammation and bone loss.
To determine the effects of RVX-208, a selective bromodomain and extra-terminal domain (BET) inhibitor targeting bromodomain 2 (BD2), on periodontal inflammation and bone loss. Macrophage-like cells (RAW264.7) and human gingival epithelial cells were challenged by Porphyromonas gingivalis (Pg) with or without RVX-208. Inflammatory gene expression and cytokine production were measured by reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. RAW264.7 cells were induced to osteoclast differentiation. After RVX-208 treatment, osteoclast differentiation was evaluated by histology, tartrate-resistant-acid-phosphatase (TRAP) activity and the expression of osteoclast-specific genes. The effect of RVX-208 on osteoclast transcriptome was studied by RNA sequencing. Periodontitis was induced in rats by ligature and local RVX-208 treatment was administered every other day. Alveolar bone loss was measured by micro-computed tomography. RVX-208 inhibited inflammatory gene expression and cytokine production in Pg-infected cells. Osteoclast differentiation was inhibited by RVX-208, as evidenced by reduced osteoclast number, TRAP activity and osteoclast-specific gene expression. RVX-208 displayed a more selective and less profound suppressive impact on transcriptome compared with pan-BET inhibitor, JQ1. RVX-208 administration prevented the alveolar bone loss in vivo. RVX-208 regulated both upstream (inflammatory cytokine production) and downstream (osteoclast differentiation) events that lead to periodontal tissue destruction, suggesting that it may be a promising 'epi-drug' for the prevention of periodontitis.


Single dose kinetic study of the triple combination mefloquine/sulphadoxine/pyrimethamine (Fansimef) in healthy male volunteers.
A single dose pharmacokinetic study of a combined antimalarial formulation of mefloquine, sulphadoxine and pyrimethamine (Fansimef) has been performed in 10 healthy adult male Malaysian volunteers. The dose consisted of two tablets containing 250 mg mefloquine base, 500 mg sulphadoxine base and 25 mg pyrimethamine base each. Plasma concentrations of mefloquine and pyrimethamine were measured by GC-ECD, those of sulphadoxine by h.p.l.c. Time to peak concentrations (mean +/- s.d. for mefloquine (5.70 +/- 0.95 h), sulphadoxine (3.75 +/- 2.03 h) and pyrimethamine (3.30 +/- 1.98 h) were similar to those observed by others after administration of the single compounds. This was also true for elimination half-lives (t1/2). The t1/2s for mefloquine, sulphadoxine and pyrimethamine were 387 +/- 98 h, 255 +/- 61 h and 114 +/- 42 h, respectively.


[Use of the harmonic scalpel for harvesting radial artery as a conduit for myocardial revascularization].
Radial artery (RA) as a conduit for coronary artery bypass grafting (CABG) was introduced in 1973 by Carpantier and within two years its use was abondoned because of high incidence of narrowing and occlusion. The reason for early RA's graft failure became clear in the late 1980s and it was its propensity for vasospasm. In recent years in conjuction with availability of antispasm agents and less invasive harvesting techniques, the RA is increasingly used for CABG. The RA has become the second arterial graft of choice after the internal thoracic artery, mainly because of its promising patency rates. In order to avoid graft traumatization less invasive techniques have been introduced lately. The purpose of this paper was to asses the clinical effect of harvesting RA with the use of the Harmonic Scalpel. We examined the results of this technique among 140 patients operated in our Department in years 2005 and 2006.


Induction of small cell lung cancer by somatic inactivation of both Trp53 and Rb1 in a conditional mouse model.
Small cell lung cancer (SCLC) is a highly aggressive human tumor with a more than 95% mortality rate. Its ontogeny and molecular pathogenesis remains poorly understood. We established a mouse model for neuroendocrine (NE) lung tumors by conditional inactivation of Rb1 and Trp53 in mouse lung epithelial cells. Mice carrying conditional alleles for both Rb1 and Trp53 developed with high incidence aggressive lung tumors with striking morphologic and immunophenotypic similarities to SCLC. Most of these tumors, which we designate MSCLC (murine small cell lung carcinoma), diffusely spread through the lung and gave rise to extrapulmonary metastases. In our model, inactivation of both Rb1 and p53 was a prerequisite for the pathogenesis of SCLC.


Necrotizing Fasciitis: A Life-Threatening Infection Due to Clostridium Species.
Necrotizing fasciitis (NF), soft tissue infections, are rare but rapidly progressive and life-threatening infections with high morbidity and mortality rates. Early detection and intervention by physicians are paramount in mortality prevention. We present a case report of a 77-year-old female who presented with extensive NF due to a Clostridium septicum infection.


Kaposi's sarcoma in renal transplant recipients.
Kaposi's sarcoma (KS) is a spindle-shaped vascular cell tumor that occurs in the skin, lymphoid, respiratory and gastrointestinal tissues. It may resemble aggressive malignant neoplasm in HIV-related or in post-transplant types but classic form may behave as benign, potentially controllable and reversible hyperplasia. KS lesions from the onset are dispersed and multicentric. KS probability increases in solid organ transplant recipients (approximately 3/1000 patients). KS occurrence is associated with: type and dose of immunosuppression, chronic stimulation by foreign allograft antigens, viral infections (Herpes virus 8), anti rejection and induction therapy, etc. 90% of KS cases appear as dark blue or purplish macular lesions that may form nodular tumors. Histological picture shows networks of spindle shaped cells and vascular spaces surrounded by an endothelial cell layer. There is no uniform schema of KS treatment in renal transplant recipients. Immunosuppression must be reduced to the lowest levels which preserve allograft function. CsA should be converted to mofetil mycophenolate or mTOR-inhibitors. After conversion to MMF regression of KS was observed, although low therapeutic MMF doses seem to be appropriate. Sirolimus seems to inhibit the growth of established vascularized tumors and this effect is best realized with relatively low immunosuppressive doses of drug.


Protonation-State Dependence of Hydration and Interactions in the Two Proton-Conducting Channels of Cytochrome c Oxidase.
Cytochrome c Oxidase (CcO), a membrane protein of the respiratory chain, pumps protons against an electrochemical gradient by using the energy of oxygen reduction to water. The ("chemical") protons required for this reaction and those pumped are taken up via two distinct channels, named D-channel and K-channel, in a step-wise and highly regulated fashion. In the reductive phase of the catalytic cycle, both channels transport protons so that the pumped proton passes the D-channel before the "chemical" proton has crossed the K-channel. By performing molecular dynamics simulations of CcO in the O→E redox state (after the arrival of the first reducing electron) with various combinations of protonation states of the D- and K-channels, we analysed the effect of protonation on the two channels. In agreement with previous work, the amount of water observed in the D-channel was significantly higher when the terminal residue E286 was not (yet) protonated than when the proton arrived at this end of the D-channel and E286 was neutral. Since a sufficient number of water molecules in the channel is necessary for proton transport, this can be understood as E286 facilitating its own protonation. K-channel hydration shows an even higher dependence on the location of the excess proton in the K-channel. Also in agreement with previous work, the K-channel exhibits a very low hydration level that likely hinders proton transfer when the excess proton is located in the lower part of the K-channel, that is, on the N-side of S365. Once the proton has passed S365 (towards the reaction site, the bi-nuclear centre (BNC)), the amount of water in the K-channel provides hydrogen-bond connectivity that renders proton transfer up to Y288 at the BNC feasible. No significant direct effect of the protonation state of one channel on the hydration level, hydrogen-bond connectivity, or interactions between protein residues in the other channel could be observed, rendering proton conductivity in the two channels independent of each other. Regulation of the order of proton uptake and proton passage in the two channels such that the "chemical" proton leaves its channel last must, therefore, be achieved by other means of communication, such as the location of the reducing electron.


Acoustical scattering by radially stratified scatterers.
A recursive solution procedure is developed to analyze the acoustical scattering by multilayer concentric circular cylindrical scatterers. The procedure is based on multiple scattering in the single-scatterer methodology originally proposed by one of the authors. The solution for a scatterer having an arbitrary number of layers is solved by recursively using the solution for a dual-layer scatterer. The solution procedure and its implementation are extensively validated. Computational characteristics, including potential pitfalls and their avoidance, are explored. The solution procedure can be used to analyze scatterers with continuously varying properties in the radial direction by approximating such a scatterer as a multilayer system. A comprehensive numerical example shows an interesting phenomenon: when a planar wave impinges onto a cooling tube in air, instead of forming a shadow zone, a strongly collimated beam is formed behind the cooling tube. This phenomenon can be explained as due to the gradient-index acoustical lens that is created around the cooling tube, which bends the sound and collimates it in the forward direction.


A Systematic Comparison Identifies an ATP-Based Viability Assay as Most Suitable Read-Out for Drug Screening in Glioma Stem-Like Cells.
Serum-free culture methods for patient-derived primary glioma cultures, selecting for glioma stem-like cells (GSCs), are becoming the gold standard in neurooncology research. These GSCs can be implemented in drug screens to detect patient-specific responses, potentially bridging the translational gap to personalized medicine. Since numerous compounds are available, a rapid and reliable readout for drug efficacies is required. This can be done using approaches that measure viability, confluency, cytotoxicity, or apoptosis. To determine which assay is best suitable for drug screening, 10 different assays were systematically tested on established glioma cell lines and validated on a panel of GSCs. General applicability was assessed using distinct treatment modalities, being temozolomide, radiation, rapamycin, and the oncolytic adenovirus Delta24-RGD. The apoptosis and cytotoxicity assays did not unequivocally detect responses and were excluded from further testing. The NADH- and ATP-based viability assays revealed comparable readout for all treatments; however, the latter had smaller standard deviations and direct readout. Importantly, drugs that interfere with cell metabolism require alternative techniques such as confluency monitoring to accurately measure treatment effects. Taken together, our data suggest that the combination of ATP luminescence assays with confluency monitoring provides the most specific and reproducible readout for drug screening on primary GSCs.


Genome-wide expression analysis of Burkholderia pseudomallei infection in a hamster model of acute melioidosis.
Burkholderia pseudomallei is the causative agent of melioidosis and represents a potential bioterrorism threat. In the current studies we have examined gene expression in B. pseudomallei in an animal model of acute melioidosis using whole-genome microarrays. Gene expression profiles were generated by comparing transcriptional levels of B. pseudomallei-expressed genes in infected hamster organs including liver, lung, and spleen following intraperitoneal and intranasal routes of infection to those from bacteria grown in vitro. Differentially expressed genes were similar in infected livers irrespective of the route of infection. Reduced expression of a number of housekeeping genes suggested a lower bacterial growth rate during infection. Energy production during growth in vivo involved specific biochemical pathways such as isomerization of 3-phosphoglycerate, catabolism of d-glucosamine and inositol, and biosynthesis of particular amino acids. In addition, the induction of genes known to be involved in oxidative phosphorylation including ubiquinol oxidase, ferredoxin oxidoreductase, and formate dehydrogenase enzymes suggested the use of alternative pathways for energy production, while the expression of genes coding for ATP-synthase and NADH-dehydrogenase enzymes was reduced. Our studies have identified differentially expressed genes which include potential virulence genes such as those for a putative phospholipase C and a putative two-component regulatory system, and they have also provided a better understanding of bacterial metabolism in response to the host environment during acute melioidosis.


Diagnosis and treatment of dural arteriovenous fistulas.
Dural arteriovenous fistulas (DAVFs) are abnormal vascular connections located within the dura mater which are thought to be promoted by venous hypertension and venous sinus thrombosis. The symptoms associated with DAVFs depend on the direction and adequacy of venous drainage pathways, the amount of arteriovenous shunting and specific location of the fistula. Our experience over a period of eight years with 268 patients suffering from cranial DAVFs in the transverse, sigmoid, superior sagittal, ethmoidal, inferior and superior petrosal, cavernous, and marginal sinuses are presented. The clinical presentation, radiographic evaluation, and treatment modalities for DAVFs in each of these locations are summarized.


Identification of skin-expressed genes possibly associated with wool growth regulation of Aohan fine wool sheep.
Sheep are valuable resources for the animal fibre industry. Therefore, identifying genes which regulate wool growth would offer strategies for improving the quality of fine wool. In this study, we employed Agilent sheep gene expression microarray and proteomic technology to compare the gene expression patterns of the body side (hair-rich) and groin (hairless) skins of Aohan fine wool sheep (a Chinese indigenous breed). Comparing the body side to the groin skins (S/G) of Aohan fine wool sheep, the microarray study revealed that 1494 probes were differentially expressed, including 602 more highly expressed and 892 less highly expressed probes. The microarray results were verified by means of quantitative PCR. Cluster analysis could distinguish the body side skin and the groin skin. Based on the Database for Annotation, Visualization and Integrated Discovery (DAVID), 38 of the differentially expressed genes were classified into four categories, namely regulation of receptor binding, multicellular organismal process, protein binding and macromolecular complex. Proteomic study revealed that 187 protein spots showed significant (p < 0.05) differences in their respective expression levels. Among them, 46 protein entries were further identified by MALDI-TOF/MS analyses. Microarray analysis revealed thousands of differentially expressed genes, many of which were possibly associated with wool growth. Several potential gene families might participate in hair growth regulation. Proteomic analysis also indentified hundreds of differentially expressed proteins.


[Epidemiological analysis on mortality of cancer in China, 2015].
Objective: To understand the distribution of cancer deaths in China in 2015 and provide reference for the prevention and control of cancer. Methods: Based on the results of Global Burden of Disease 2015, the cancer death distributions in different age groups, sex groups, provinces or by different malignant tumor in Chinese were described. Results: The age-standardized mortality rate of cancer was 159.01/100 000 in China in 2015. The mortality rate was highest in age group ≥70 years (1 102.73/100 000), and lowest in age group 5-14 years (5.40/100 000). The mortality rate in males was 2.15 times higher than that in females. The first 5 provinces with high cancer mortality rate were Anhui, Qinghai, Sichuan, Guangxi and Henan. Lung cancer, liver cancer, stomach cancer, esophageal cancer and colorectal cancer ranked 1-5 in term of mortality rate. Conclusion: The cancer mortality differed with age, gender, area and different malignant tumors, suggesting the necessity to develop targeted prevention and control strategies.


Dental hygiene students and faculty attitudes and utilization of a single source electronic textbook platform.
Transitioning to interactive e-textbooks has been considered revolutionary for enhancing student learning. However, adopting this technology has been met with hesitation. This study investigates student and faculty attitudes and utilization of mandatory e-textbooks in a dental hygiene program. In 2017, an online questionnaire was distributed to students and a focus group was conducted with faculty to examine their perspectives about using VitalSource™. Using a 5-point Likert scale with five indicating strongly agree, the questionnaire examined convenience; compatibility with learning style; perceived enjoyment; and usefulness. Open-ended questions captured benefits and challenges. The focus group gathered faculty perspectives. Questionnaire data were analysed using descriptive statistics. Data from the open-ended questionnaire questions and focus group transcript followed a narrative analysis process. Survey response was 48% (n = 105). Students scored all factors below neutral. Results from four categories showed convenience (M = 2.75, SD = 0.92); compatibility (M = 1.93, SD = 0.83); perceived effectiveness (M = 2.15, SD = 0.90); and perceived usefulness (M = 2.36, SD = 1.04). A high correlation between all factors suggests they were uniformly rated by students. Majority of students (71%) did not use a textbook greater than once a month. Narrative analysis revealed few benefits; challenges included technical glitches, eyestrain, cost and inability to choose books as desired. Faculty's perspectives aligned with the students, but they appreciated portability of texts and quality of clinical images. Students strongly disliked the platform and the online medium and do not frequently access e-textbooks but rely on PowerPoint handouts for studying. Faculty felt e-textbooks do not align with positive learning experiences.


Cooperative binding of the tandem WW domains of PLEKHA7 to PDZD11 promotes conformation-dependent interaction with tetraspanin 33.
Pleckstrin homology domain-containing A7 (PLEKHA7) is a cytoplasmic protein at adherens junctions that has been implicated in hypertension, glaucoma, and responses to Staphylococcus aureus α-toxin. Complex formation between PLEKHA7, PDZ domain-containing 11 (PDZD11), tetraspanin 33, and the α-toxin receptor ADAM metallopeptidase domain 10 (ADAM10) promotes junctional clustering of ADAM10 and α-toxin-mediated pore formation. However, how the N-terminal region of PDZD11 interacts with the N-terminal tandem WW domains of PLEKHA7 and how this interaction promotes tetraspanin 33 binding to the WW1 domain is unclear. Here, we used site-directed mutagenesis, glutathione S-transferase pulldown experiments, immunofluorescence, molecular modeling, and docking experiments to characterize the mechanisms driving these interactions. We found that Asp-30 of WW1 and His-75 of WW2 interact through a hydrogen bond and, together with Thr-35 of WW1, form a binding pocket that accommodates a polyproline stretch within the N-terminal PDZD11 region. By strengthening the interactions of the ternary complex, the WW2 domain stabilized the WW1 domain and cooperatively promoted the interaction with PDZD11. Modeling results indicated that, in turn, PDZD11 binding induces a conformational rearrangement, which strengthens the ternary complex, and contributes to enlarging a "hydrophobic hot spot" region on the WW1 domain. The last two lipophilic residues of tetraspanin 33, Trp-283 and Tyr-282, were required for its interaction with PLEKHA7. Docking of the tetraspanin 33 C terminus revealed that it fits into the hydrophobic hot spot region of the accessible surface of WW1. We conclude that communication between the two tandem WW domains of PLEKHA7 and the PLEKHA7-PDZD11 interaction modulate the ligand-binding properties of PLEKHA7.


Remarks on the current quality of groundwater in Vietnam.
This paper reviews the current quality of groundwater in Vietnam. In Vietnam, groundwater is obtained primarily from tubewells, which have high concentrations of pollutants such as As, Fe, Mn, and NH4+. In the areas where groundwater tests were conducted, arsenic levels ranged from 0.1-3050 μg/L, which substantially exceed the standard of 10 μg/L which has been established by the WHO. Contamination sources are distributed over a large area from the Red River Delta in the north to the Mekong River Delta in the south, putting as many as ten million people at risk of adverse health effects. Levels of arsenic and iron in sediment are strongly correlated, which indicate that the presence of arsenic in groundwater results from the reduction of arsenic bound to iron oxyhydroxides. It is important to raise awareness of these issues among the Vietnamese public by disseminating information about the negative effects of contaminated drinking water, as well as carrying out long-term research projects to identify other sources of contamination and improving water treatment technology and water management capabilities.


A novel approach for reducing toxic emissions during high temperature processing of electronic waste.
A novel approach is presented to capture some of the potentially toxic elements (PTEs), other particulates and emissions during the heat treatment of e-waste using alumina adsorbents. Waste PCBs from mobile phones were mechanically crushed to sizes less than 1mm; their thermal degradation was investigated using thermo-gravimetric analysis. Observed weight loss was attributed to the degradation of polymers and the vaporization of organic constituents and volatile metals. The sample assembly containing PCB powder and adsorbent was heat treated at 600°C for times ranging between 10 and 30min with air, nitrogen and argon as carrier gases. Weight gains up to ∼17% were recorded in the adsorbent thereby indicating the capture of significant amounts of particulates. The highest level of adsorption was observed in N2 atmosphere for small particle sizes of alumina. SEM/EDS results on the adsorbent indicated the presence of Cu, Pb, Si, Mg and C. These studies were supplemented with ICP-OES analysis to determine the extent of various species captured as a function of operating parameters. This innovative, low-cost approach has the potential for utilization in the informal sector and/or developing countries, and could play a significant role in reducing toxic emissions from e-waste processing towards environmentally safe limits.


Genetic and functional characterization of the gene cluster directing the biosynthesis of putisolvin I and II in Pseudomonas putida strain PCL1445.
Pseudomonas putida PCL1445 secretes two cyclic lipopeptides, putisolvin I and putisolvin II, which possess a surface-tension-reducing ability, and are able to inhibit biofilm formation and to break down biofilms of Pseudomonas species including Pseudomonas aeruginosa. The putisolvin synthetase gene cluster (pso) and its surrounding region were isolated, sequenced and characterized. Three genes, termed psoA, psoB and psoC, were identified and shown to be involved in putisolvin biosynthesis. The gene products encode the 12 modules responsible for the binding of the 12 amino acids of the putisolvin peptide moiety. Sequence data indicate that the adenylation domain of the 11th module prioritizes the recognition of Val instead of Leu or Ile and consequently favours putisolvin I production over putisolvin II. Detailed analysis of the thiolation domains suggests that the first nine modules recognize the d form of the amino acid residues while the two following modules recognize the l form and the last module the l or d form, indifferently. The psoR gene, which is located upstream of psoA, shows high similarity to luxR-type regulatory genes and is required for the expression of the pso cluster. In addition, two genes, macA and macB, located downstream of psoC were identified and shown to be involved in putisolvin production or export.


Visible-light-responsive multielectron redox catalysis of lacunary polyoxometalates induced by substrate coordination to their lacuna.
We describe herein the efficient visible-light-responsive polyoxometalate-based multielectron photoredox catalysis induced by in situ coordination of alcohols to the lacuna of TBA4 H4 [γ-SiW10 O36 ] (I, TBA=tetra-n-butylammonium). The coordination of alcohols to the lacuna of I generated a new highest occupied molecular orbital as the electron donor level and enabled the visible-light-responsive multielectron transfer from alcohols to I, which could be utilized for aerobic alcohol oxidation and one-pot synthesis of N-arylimines starting from nitroarenes and primary alcohols.


Sex steroid receptors in endometrial cancer.
Endometrial cancer contains estrogen and progestin receptor proteins. The receptor content inversely correlates with histologic differentiation. The correlation between receptor content and histologic subtype and stage of the disease may depend upon the degree of differentiation of the tumor. The status of the peritoneal cytology and depth of myometrial invasion by tumor do not correlate with the receptor status. In general, patients with receptor-rich tumors have a better prognosis than those without receptors and respond favorably to progestin therapy. The level of the receptor protein in the tumor may also influence survival.


A large fixed bed reactor for MRI operando experiments at elevated temperature and pressure.
Recently, in situ studies using nuclear magnetic resonance (NMR) have shown the possibility to monitor local transport phenomena of gas-phase reactions inside opaque structures. Their application to heterogeneously catalyzed reactions remains challenging due to inherent temperature and pressure constraints. In this work, an NMR-compatible reactor was designed, manufactured, and tested, which can endure high temperatures and increased pressure. In temperature and pressure tests, the reactor withstood pressures up to 28 bars at room temperature and temperatures over 400 °C and exhibited only little magnetic shielding. Its applicability was demonstrated by performing the CO2 methanation reaction, which was measured operando for the first time by using a 3D magnetic resonance spectroscopic imaging sequence. The reactor design is described in detail, allowing its easy adaptation for different chemical reactions and other NMR measurements under challenging conditions.


The occupational and psychosocial impact of SARS on academic physicians in three affected hospitals.
A cross-sectional anonymous survey was administered to all directory-listed physicians within a network of three large teaching hospitals that provided care to SARS patients in Toronto. One hundred ninety-three physicians participated, 23% of whom provided direct care to SARS patients. A significantly higher rate of psychological distress was seen among physicians providing direct care to SARS patients (45.7%) than among those not providing direct care (17.7%), and physicians providing direct care reported feeling more stigmatized. Several physicians (10.9%) reported entering the hospital despite experiencing identified SARS symptoms. The most frequent SARS concerns were about the care of non-SARS patients following suspension of nonessential services and loss of physician income.


Design and structure-activity relationships of novel inhibitors of human rhinovirus 3C protease.
Human rhinovirus (HRV) is a primary cause of common cold and is linked to exacerbation of underlying respiratory diseases such as asthma and COPD. HRV 3C protease, which is responsible for cleavage of viral polyprotein in to proteins essential for viral life-cycle, represents an important target. We have designed proline- and azetidine-based analogues of Rupintrivir that target the P2 pocket of the binding site. Potency optimization, aided with X-ray crystallography and quantum mechanical calculations, led to compounds with activity against a broad spectrum of HRV serotypes. Altogether, these compounds represent alternative starting points to identify promising leads in our continual efforts to treat HRV infections.


Incidence of ESBL producers amongst Gram-negative bacilli isolated from intra-abdominal infections across India (based on SMART study, 2007 data).
This study was conducted in 9 centers spread over India from January 1 to December 31, 2007 to monitor in vitro susceptibility of Gram-negative bacilli to Group I carbapenem, ertapenem and other antimicrobials in intra-abdominal infections and to identify early changes in susceptibility pattern of community or hospital acquired organisms, with a focus on ESBL producers. Gram-negative bacilli isolated from intra-abdominal samples of patients with documented intra-abdominal infections were processed for identification by conventional/ automated methods and antimicrobial susceptibility by Micro-Scan (Siemens) MIC panel against 12 antimicrobials (3rd and 4th generation cephalosporins, Groups I and II carbapenems, amikacin, levofloxacin, amoxicillin-clavulanic acid and piperacillin-tazobactam). A total of 588 isolates were identified, of which 351 (60%) were E. coli and 114 (19%) were Klebsiella spp. 79% of E. coli and 70% of Klebsiella spp. were ESBL producers in general. 110 of E. coli and 35 of Klebsiella isolates were from community-acquired intra-abdominal infections. 80% of E. coli and 63% of Klebsiella isolates from community-acquired infections were ESBL producers, against 79% of E. coli and 73% of Klebsiella isolates from hospital-acquired infections. Amongst the ESBL-positive isolates of E. coli, 94% were susceptible in vitro to ertapenem, 96% to imipenem and 76% to piperacillin-tazobactam. For ESBL-positive isolates of Klebsiella spp., the corresponding figures were 80%, 94% and 59% respectively. The study showed a high incidence of ESBL-producers amongst Enterobacteriaceae isolates from intra-abdominal infections in both community-acquired and hospital-acquired settings across India. Ertapenem was comparable with imipenem against ESBL-positive E. coli isolates, while imipenem was more effective than ertapenem against ESBL-positive Klebsiella isolates.


Pd Nanoparticle-Loaded Smart Microgel-Based Membranes as Reusable Catalysts.
In this work, palladium-loaded smart membranes made by UV cross-linking of thermoresponsive microgels are prepared to obtain a reusable, catalytically active material which can, for example, be implemented in chemical reactors. The membranes are examined with respect to their coverage of a supporting mesh via atomic force microscopy measurements. Force indentation mapping was performed in the dried, collapsed state and in the swollen state in water to determine the Young modulus. Furthermore, we compare the catalytic activity of the membrane with the corresponding suspended colloidal nanoparticle microgel hybrids. For this purpose, the reduction of 4-nitrophenol is an established model reaction to quantify the catalytic activity by UV-vis spectroscopy. The membrane is embedded inside a continuous stirred tank reactor equipped for continuous monitoring of the reaction progress. Although catalysis with membranes shows lower catalytic activity than freely dispersed particles, membranes allow straightforward separation and recycling of the catalyst. The fabricated membranes in this work show no decrease in catalytic activity between several cycles, unlike free particles. The feasible and durable deposition of catalytically active inter-cross-linked microgel particles on commercial nylon meshes as supporting scaffolds, as demonstrated in this work, is promising for up-scaling of continuous industrial processes.


Ten-year incidence of coronary heart disease in the Honolulu Heart Program. Relationship to nutrient intake.
Nutrient intake was determined in over 8000 men of Japanese ancestry residing on the island of Oahu. Nutrient determination took place at the initial examination during the years 1965-1968. This report relates nutrient intake to the risk of developing coronary heart disease in the 10 years subsequent to the initial examination. Men who developed coronary heart disease had a lower average intake of calories, carbohydrates, starch, and vegetable protein than men who remained free of coronary heart disease. Men who developed coronary heart disease also had a higher mean intake of percentage of calories from protein, fat, saturated fatty acids, and polyunsaturated fatty acids than men who remained free of coronary heart disease. These men also had a significantly lower mean percentage of calories from carbohydrates and a higher mean ingestion of cholesterol per 1000 calories than men who remained free of coronary heart disease. In multivariate analyses including age, systolic blood pressure, serum cholesterol, cigarettes smoked per day, and physical activity index, carbohydrates, vegetable protein, percentage of calories from saturated fatty acids, and percentage of calories from polyunsaturated fatty acids are no longer significantly related to incidence.


Cooperative dementia care clinics: A new model for managing cognitively impaired patients.
Cooperative health care clinics (CHCCs), or shared medical appointments, are a healthcare innovation that can improve access and expand physicians' capacity to manage common geriatric conditions. This report describes a pilot program and working model for extending CHCCs to patients with dementia. Three cooperative dementia care clinics (CDCCs) met monthly for up to 1 year, drawing participants from a dementia clinic roster of patients and caregivers who had required continued specialty care for at least 3 months. Twenty-six of 33 eligible patient-caregiver dyads expressed interest, and 21 enrolled; five whose clinical status changed during the year withdrew and were replaced with new members. Brief introductory socialization, individualized clinical management, and an educational focus selected from problems of patients and caregivers were common to all sessions. Most participants required several types of clinical intervention and educational support. One group ended after reaching a natural termination point, and two others are ongoing at the request of participants. CDCCs can be a viable approach to increasing dementia care capacity in health systems. Formal service intervention trials to evaluate the generalizability and comparative effectiveness and economic viability of this model versus usual care are an appropriate next step.


Brain-Derived Neurotrophic Factor (BDNF) and Translocator Protein (TSPO) as Diagnostic Biomarkers for Acute Ischemic Stroke.
Brain-derived neurotrophic factor (BDNF) interacts with tropomyosin-related kinase B (TrkB) to promote neuronal growth, survival, differentiation, neurotransmitter release, and synaptic plasticity. The translocator protein (TSPO) is known to be found in arterial plaques, which are a symptom of atherosclerosis and a contributory cause of ischemic stroke. This study aims to determine the diagnostic accuracy of plasma BDNF and TSPO levels in discriminating new-onset acute ischemic stroke (AIS) patients from individuals without acute ischemic stroke. A total of 90 AIS patients (61% male, with a mean age of 67.7 ± 12.88) were recruited consecutively in a stroke unit, and each patient was paired with two age- and gender-matched controls. The sensitivity, specificity, and area of the curve between high plasma BDNF and TSPO and having AIS was determined using receiver operating characteristic curves. Furthermore, compared to the controls, AIS patients exhibited significantly higher levels of BDNF and TSPO, blood pressure, HbA1c, and white blood cells, as well as higher creatinine levels. The plasma levels of BDNF and TSPO can significantly discriminate AIS patients from healthy individuals (AUC 0.76 and 0.89, respectively). However, combining the two biomarkers provided little improvement in AUC (0.90). It may be possible to use elevated levels of TSPO as a diagnostic biomarker in patients with acute ischemic stroke upon admission.


A primary aorto-duodenal fistula associated with an inflammatory abdominal aortic aneurysm: a case report.
Primary aorto-enteric fistula (PAEF)is a serious complication of abdominal aortic aneurysm(AAA). We report a patient with PAEF associated with inflammatory AAA who underwent emergent surgery. A 52-year-old male presented with recurrent hematemesis. A computer tomography scan showed a sealed rupture of the AAA adjacent to the duodenum. At surgery, a coin-sized PAEF was noted. The aorta was replaced with a Dacron graft in situ . Histological examination revealed the characteristics of an inflammatory AAA. The postoperative course was uneventful, and there has been no evidence of infection during a follow-up period of 3 years. We discuss the etiologic and surgical considerations regarding this unusual entity.


High pressure Raman spectroscopic study of deuterated gamma-glycine.
Raman spectroscopic investigations of deuterated gamma-glycine, carried out up to 21 GPa, indicate emergence of a new phase, which is similar to the delta-phase, reported to be formed from the undeuterated gamma-glycine at 3 GPa and the transformation to this phase is complete by 6 GPa. Observed pressure -induced variations in CD2 and N-D stretching modes indicate significant changes in the hydrogen-bonding interactions. Around approximately 15 GPa, splitting of CD2 and C-C stretching modes and discontinuous changes in the slope of CO2 and N-D stretching modes indicate another structural rearrangement across this pressure. The Raman spectra of retrieved phase at ambient conditions suggest that it may be a layered structure similar to the zeta-phase reported to be formed on decompression of the nondeuterated delta-glycine.


Evidence for degradation of abnormal prion protein in tissues from sheep with scrapie during composting.
This study investigated whether the abnormal prion protein (PrP(Sc)) in tissues from sheep with scrapie would be destroyed by composting. Tissues from sheep naturally infected with scrapie were placed within fiberglass mesh bags and buried in compost piles for 108 d in experiment 1 or 148 d in experiment 2. The temperature in the compost piles rose quickly; it was above 60 degrees C for about 2 wk and then slowly declined to the ambient temperature. Before composting, PrPSc was detected in all the tissues by Western blotting. In experiment 1, PrPsc was not detected after composting in the tissue remnants or the surrounding sawdust. In experiment 2, 1 of 5 specimens tested negative after composting, whereas PrP(Sc) was detected in the other 4 bags, though in reduced amounts compared with those before composting. Tissue weights were reduced during composting. Analysis of the tissue remnants for microbial 16S ribosomal DNA demonstrated that there were more diverse microbes involved in experiment 1 than in experiment 2 and that the guanine and cytosine content of the microbial 16S DNA was higher in the specimens of experiment 1 than in those of experiment 2, which suggests greater dominance of thermophilic microbes in experiment 1. These results indicate that composting may have value as a means for degrading PrP(Sc) in carcasses and other wastes.


LOGISTIC REGRESSION FOR EMPIRICAL STUDIES OF MULTIVARIATE SELECTION.
Understanding the mechanics of adaptive evolution requires not only knowing the quantitative genetic bases of the traits of interest but also obtaining accurate measures of the strengths and modes of selection acting on these traits. Most recent empirical studies of multivariate selection have employed multiple linear regression to obtain estimates of the strength of selection. We reconsider the motivation for this approach, paying special attention to the effects of nonnormal traits and fitness measures. We apply an alternative statistical method, logistic regression, to estimate the strength of selection on multiple phenotypic traits. First, we argue that the logistic regression model is more suitable than linear regression for analyzing data from selection studies with dichotomous fitness outcomes. Subsequently, we show that estimates of selection obtained from the logistic regression analyses can be transformed easily to values that directly plug into equations describing adaptive microevolutionary change. Finally, we apply this methodology to two published datasets to demonstrate its utility. Because most statistical packages now provide options to conduct logistic regression analyses, we suggest that this approach should be widely adopted as an analytical tool for empirical studies of multivariate selection.


Epstein-Barr virus inhibits the development of dendritic cells by promoting apoptosis of their monocyte precursors in the presence of granulocyte macrophage-colony-stimulating factor and interleukin-4.
Epstein-Barr virus (EBV) is a tumorigenic human herpesvirus that persists for life in healthy immunocompetent carriers. The viral strategies that prevent its clearance and allow reactivation in the face of persistent immunity are not well understood. Here we demonstrate that EBV infection of monocytes inhibits their development into dendritic cells (DCs), leading to an abnormal cellular response to granulocyte macrophage-colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) and to apoptotic death. This proapoptotic activity was not affected by UV inactivation and was neutralized by EBV antibody-positive human sera, indicating that binding of the virus to monocytes is sufficient to alter their response to the cytokines. Experiments with the relevant blocking antibodies or with mutated EBV strains lacking either the EBV envelope glycoprotein gp42 or gp85 demonstrated that interaction of the trimolecular gp25-gp42-gp85 complex with the monocyte membrane is required for the effect. Our data provide the first evidence that EBV can prevent the development of DCs through a mechanism that appears to bypass the requirement for viral gene expression, and they suggest a new strategy for interference with the function of DCs during the initiation and maintenance of virus-specific immune responses.


Protic Ionic Liquids for Lignin Extraction-A Lignin Characterization Study.
Protic ionic liquids (PILs) have been established as effective solvents for the selective extraction and recovery of lignin from lignocellulosic biomass. In this study, we utilize extensive analytical techniques to characterize the PIL-extracted lignins to (1) expand on the physical/chemical structure, and to (2) develop a better understanding of the mechanism behind the lignin dissolution process. The PIL-lignins were characterized using elemental and FT-IR analyses, alongside molecular weight distribution and chemical modeling via MM2. For the more ionic pyrrolidinium acetate ([Pyrr][Ac]), there is an increase in the fragmentation of lignin, resulting in lignin with a smaller average molecular weight and a more uniform dispersity. This lends better understanding to previous findings indicating that higher ionicity in a PIL leads to increased lignin extraction.


Tricyclic 2,4-diaminopyrimidines with broad antifolate activity and the ability to inhibit Pneumocystis carinii growth in cultured human lung fibroblasts in the presence of leucovorin.
A selected number of 1,3-diaminobenzo[f]quinazolines and 1,3-diamino-5,6-dihydrobenzo[f]quinazolines, which may be viewed as tricyclic analogues of the lipid-soluble antifolates pyrimethamine (PM), metoprine (DDMP), and etoprine (DDEP), were tested as inhibitors of purified dihydrofolate reductase (DHFR) from WI-L2 lymphoblasts, and as inhibitors of the growth of Streptococcus faecium ATCC 8043 and L1210 murine leukemia cells in culture. In addition, these tricyclic compounds were tested for antimalarial activity against Plasmodium berghei in mice, and for the ability to inhibit the growth of Pneumocystis carinii trophozoites in WI-38 human lung fibroblast cultures in the presence of leucovorin (LV). The most potent analogues were those with chlorine substitution in the ring distal to the 2,4-diaminopyrimidine moiety. Fully aromatic compounds tended to be more active than those in which the 5,6-bond was reduced, suggesting that planarity favors binding to the DHFR active site and may be favorable for cellular uptake. Several of the 2,4-diaminopyrimidine analogues showed greater potency than PM, DDMP or DDEP, and were more nearly comparable to the bicyclic 2,4-diaminopyrimidine antifolates trimetrexate (TMQ) or piritrexim (BW301U), which are known to be selectively toxic to P. carinii in the presence of LV. Two of the tricyclic compounds, 1,3-diamino-8-chlorobenzo[f]quinazoline and 1,3-diamino-9-chlorobenzo[f]quinazoline, proved to have activity similar to TMQ and BW301U in this system.