Activated carbon prepared from Brazil nut shells towards phenol removal from aqueous solutions.
The Brazil nut shell was used as a precursor material for preparing activated carbon by chemical activation with potassium hydroxide. The obtained material (BNSAC) was characterized, and the adsorptive features of phenol were investigated. The characterization showed that the activated carbon presented several rounded cavities along the surface, with a specific surface area of 332 m2 g-1. Concerning phenol adsorption, it was favored using an adsorbent dosage of 0.75 g L-1 and pH 6. The kinetic investigation revealed that the system approached the equilibrium in around 180 min, and the Elovich model represented the kinetic curves. The Sips model well represented the equilibrium isotherms. In addition, the increase in temperature from 25 to 55 °C favored the phenol adsorption, increasing the maximum adsorption capacity value (qs) from 83 to 99 mg g-1. According to the estimated thermodynamic parameters, the adsorption was spontaneous, favorable, endothermic, and governed by physical interactions. Therefore, the Brazil nut shell proved a good precursor material for preparing efficient activated carbon for phenol removal.


Interaction of protein synthesis initiation factor 2 from Xenopus laevis oocytes with GDP and GTP analogs.
The structural specificity of the purified protein synthesis initiation factor 2 (eIF-2) from X. laevis ovary towards analogs of GTP and GDP was studied. The relative affinity of the structural analogs was measured by their capacity to inhibit the formation of the [3H]GDP X eIF-2 binary complex. The results obtained demonstrate that modifications in the ribose moiety are well tolerated by eIF-2 which binds dGTP, 2',3'-dialdehyde GTP (oGTP) and 2',3'-dialdehyde GDP (oGDP) and even the dinucleotide cytidylyl(5'-3')guanosine 5'-triphosphate (pppGpC). Substitution in the polyphosphate chain by phosphorothioate groups in the beta and gamma positions (GDP beta S or GTP gamma S) does not abolish the affinity for the nucleotides and the presence of an imido group between the beta and gamma phosphates in guanyl-5'-yl imidodiphosphate (GppNHp) still permits a weaker but significant binding. Guanine 5'-O-(2-fluorodiphosphate) (GDP beta F) has an affinity considerably lower than GDP beta S. Methylation of position 7 of the guanine (7-m GDP), however, completely eliminates the interaction of GDP with eIF-2. The analogs tested can be listed in the following order of descending affinities: GDP greater than GDP beta S greater than oGDP greater than or equal to GTP gamma S greater than GDP beta F greater than pppGpC greater than GTP greater than GppNHp greater than oGTP much greater than 7-m GDP. Assays of the capacity of GTP analogs to form a ternary complex of the type met-tRNAi X GTP X eIF-2 or of GDP analogs to inhibit the formation of this complex reflect, in general, the same order of relative affinities except for pppGpC, which is weaker in its capacity to form a ternary complex than GppNHp or oGTP, although it has a higher affinity than these compounds in the formation of a binary complex.


Human beta-glucuronidase. Measurement of its activity in gallbladder bile devoid of intrinsic interference.
Our purpose is to develop a standard method for preparing the bile for beta-glucuronidase determination by removal of bile acids and conjugated bilirubin which interfere with its activity. The bile acids and conjugated bilirubin in their purified solutions and in the diluted gallbladder biles could be extracted completely with cholestyramine in powder form or tetrahexylammonium chloride (THAC) in chloroform or ethyl acetate. The enzyme was, however, partially precipitated with cholestyramine and denatured by chloroform but not by ethyl acetate. A standard procedure, therefore, includes extraction of the diluted gallbladder bile with THAC in ethyl acetate, followed by determination of the maximal velocity (Vmax) of the enzyme by a kinetic method employing phenolphthalein glucuronide as the substrate. The average Vmax of beta-glucuronidase in the 20 normal gallbladder biles was 165 +/- 86 nmol/min/ml (mean +/- SD), a 23.5-fold increase over the activity before extraction. The measured activity represented the true activity of the enzyme in the bile for recovery of activity of the enzyme added to the bile was practically complete.


MicroRNA-128a represses chondrocyte autophagy and exacerbates knee osteoarthritis by disrupting Atg12.
Chondrocyte loss is a prominent feature of osteoarthritis (OA). Autophagy is indispensable in maintaining the metabolic activities of cells exposed to deleterious stress. The contribution of microRNA signaling to chondrocyte autophagy in OA development remains elusive. We uncovered an association between poor autophagy and increased miR-128a expressions in articular chondrocytes of patients with end-stage knee OA and in a rat anterior cruciate ligament transection (ACLT) model for OA development. Cartilage matrix degradation and severe OA histopathology was evident upon forced miR-128a expression within the articular compartment. Intra-articular injections with miR-128a antisense oligonucleotide stabilized chondrocyte autophagy and slowed ACLT-mediated articular tissue destruction, including cartilage erosion, synovitis, osteophyte formation, and subchondral plate damage. In vitro, miR-128 signaling hindered Atg12 expression, LC3-II conversion, and autophagic puncta formation through targeting the 3'-untranslated region of Atg12. It increased apoptotic programs, diminishing cartilage formation capacity of articular chondrocytes. Inactivating histone methyltransferase EZH2 reduced methyl histone H3K27 enrichment in the miR-128a promoter and upregulated miR-128a transcription in inflamed chondrocytes. Taken together, miR-128a-induced Atg12 loss repressed chondrocyte autophagy to aggravate OA progression. EZH2 inactivation caused H3K27 hypomethylation to accelerate miR-128a actions. Interruption of miR-128a signaling attenuated chondrocyte dysfunction and delayed OA development. Our data provide new insights into how miR-128a signaling affects chondrocyte survival and articular cartilage anabolism and highlight the potential of miR-128a targeting therapy to alleviate knee OA.


Two-dimensional echocardiographic assessment of bioprosthetic valve dysfunction and infective endocarditis.
Two-dimensional echocardiography of Hancock porcine heterograft valves was evaluated by correlation with clinical, hemodynamic, angiographic and pathologic findings in 80 patients. Ninety-five aortic and mitral bioprostheses were categorized by the type of valvular abnormality: group I, dysfunction due to primary tissue failure (41 valves); group II, dysfunction due to paravalvular leakage without infection (5 valves); group III, infective endocarditis with or without hemodynamic dysfunction (28 valves); and group IV, control cases without dysfunction or infection (21 valves). Increased size of a bioprosthetic leaflet image (minimal dimensions 3 x 5 mm) was observed in 46% (19 of 41) of cases with primary tissue failure and in 62% (10 of 16) of cases with leaflet vegetations due to endocarditis. Prolapse of leaflet echoes to below the level of the bioprosthetic sewing ring occurred in 76% (28 of 37) of cases with torn leaflets and also in 46% (6 of 13) of valves with vegetations on intact leaflets. Antegrade extension of leaflet echoes to beyond the level of the stents, observed in 4 of 16 cases with leaflet vegetations, was the only echocardiographic sign distinguishing leaflet infection from leaflet degeneration. Aortic bioprostheses with ring dehiscence affecting 40 to 90% of the anular circumference showed motion discordant with the motion of the adjacent aortic root and native anulus. Although echocardiographic abnormalities are frequently observed with bioprosthetic leaflet degeneration or infection, the echocardiographic appearance often does not distinguish between these two major complications and is best interpreted concurrently with other clinical and laboratory assessment.


Characterization of the murine IgG Fc receptor III and IIB gene promoters: a single two-nucleotide difference determines their inverse responsiveness to C5a.
The two low affinity IgG Fc receptors (FcgammaR), FcgammaRIII and FcgammaRIIB, are coexpressed on myeloid effector cells, and their genes, as reported here, are positively and negatively regulated by both C5a and interferon-gamma through different signaling mechanisms. Two 48- and 43-bp sequences (C5a-inductive region (CIR) and C5a-suppressive region (CSR)) in the FcgammaRIII and FcgammaRIIB 5'-flanking regions that are necessary for C5a induction and suppression, respectively, are defined. Sequence analysis of the CIR and CSR, which localize apart from the interferon-gamma-responsive regions in each gene, revealed the presence of a novel element that differs by two nucleotides between FcgammaRIII and FcgammaRIIB. Mutation analysis of the CIR and CSR showed that this small difference determines inverse responsiveness in an FcgammaR gene context-dependent manner. Our study suggests that C5a uses similar DNA motifs (defined as GTGAXXTCCA) in both pathways of transcriptional induction and suppression of FcgammaRIII and FcgammaRIIB.


Sarcoidosis.
Sarcoidosis is a disease of unknown etiology with protean manifestations. Its history is revealed in its many eponymic syndromes. The histologic features are nonspecific, as are most of the clinical manifestations. The diagnosis is made by exclusion. The immunologic abnormalities are fascinating, with features of both hyperactivity and depression. Therapy is nonspecific and generally symptomatic.


[Safety signal detection by the French Addictovigilance Network: Innovative methods of investigation, examples and usefulness for public health].
The French Addictovigilance Network aims to monitor all psychoactive substances with abuse potential including prescription drugs and other legal and illegal substances such as new psychoactive substances (NPS) and its consequences in humans. Created in 1990 through a network of regional addictovigilance centres covering the entire country, these pharmacologists with expertise in addictovigilance have developed interface with different partners (physicians, toxicologists, network of community pharmacies, addictology care centers…) and implemented several original tools of pharmacosurveillance (such as DRAMES [death related to the abuse of medicines] in strong collaboration with toxicologists or such OPPIDUM [observation of illegal products and misuse of psychotropic medications]), complementary to the spontaneous reporting. A such multidimensional approach including proactive surveillance by these tools and also among several heterogenous data sources (such as data from hospitals or claims database) is able to detect early addictovigilance signals and warnings as illustrated with three following examples: cannabis use and acute serious cardiovascular disorders, new synthetic opioids (ocfentanil, carfentanil) and severe opiate overdose or deaths, the diverted use of psychoactive drugs (codeine analgesics or sedative H1 antihistamines called purple drank) by adolescents and young adults. The choice of a broad strategy and the multifaceted system implemented by the French Addictovigilance Network using elements of pharmacology (fundamental, clinical, pharmacoepidemiology) expertise is an innovative method to detect early addictovigilance signals, and to describe its characteristics in order to increase awareness of psychoactive substances by patients, users and health professionals.


Temperature triggering of kinetically trapped self-assemblies in citrem-phospholipid nanoparticles.
Lyotropic non-lamellar liquid crystalline (LLC) nanoparticles are attractive nanocarriers for drug delivery, particularly for the solubilization of poorly water-soluble drugs. Due to the reported problems of complement activation and cytotoxicity of most investigated Pluronic F127-stabilized cubosomes and hexosomes, there is an interest in introducing safe stabilizers for these LLC nanodispersions. Citrem appears to be the stabilizer of choice for the colloidal stabilization of these LLC nano-self-assemblies owing to its hemocompatiblity and poor activation of the complement system. This anionic food-grade emulsifier in combination with soy phosphatidylcholine (SPC) can be used to introduce a library of hemocompatible lamellar and non-lamellar liquid crystalline nanodispersions at different lipid compositions. We found that batch-to-batch variability in citrem composition is associated with slight alterations in the size, structural characteristics, and surface charge of the produced citrem/SPC nanoparticles. Further, we report on the temperature-triggered alterations in these nano-self-assemblies at different lipid compositions by using synchrotron small angle X-ray scattering (SAXS). The addition of citrem at different temperatures induces lamellar to non-lamellar structural transitions as evident from the appearance of inverse bicontinuous cubic Pn3m and discontinuous hexagonal (H2) phases, respectively, upon increasing citrem concentration and varying temperature in the range of 5-59 °C. Citrem/SPC nanoparticles are attractive for use in the development of nanocarriers for drug delivery owing to their structural tunability and hemocompatiblity.


Neuroanatomy of sepsis-associated encephalopathy.
This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2017. Other selected articles can be found online at http://ccforum.com/series/annualupdate2017 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901 .Originally published in the Annual Update in Intensive Care and Emergency Medicine 2017. The number of authors differs in the two versions due to constraints regarding the number of authors in the Annual Update in Intensive Care and Emergency Medicine. In the Annual Update version of the review, the three senior authors appear in the acknowledgement section. In the Critical Care version, these three senior authors appear as full authors of the manuscript. All authors helped draft and revise the manuscript for critical intellectual content.


Effects of PEEP on extravascular lung water and central blood volume in the dog.
Twenty-four mongrel dogs were anaesthetized and ventilated mechanically in the supine position. Extravascular lung water (EVLW) and central blood volume (CBV) were measured with a double indicator (dye/cold) dilution technique. Both indicators were detected intravascularly in the aortic root with a fibreoptic thermistor catheter. Seven dogs ventilated with a positive end-expiratory pressure (PEEP) of 1.0 kPa (10 cmH2O) for a short period of time (less than 20 min) displayed no significant change in EVLW as measured with the indicator dilution technique (= EVLWi), while reductions were seen in both CBV (15%, P less than 0.01) and cardiac output (CO-thermodilution technique) (10%, P less than 0.05). Another seven dogs ventilated with a PEEP of 1.0 kPa for 8 h showed a gradual increase in EVLWi. After 8 h, a mean increase of 34% (P less than 0.01) was recorded, and the increase was also verified by post-mortem gravimetric determination of EVLW (= EVLWg), displaying an increase of 61% (P less than 0.01). In five dogs ventilated with zero end-expiratory pressure (ZEEP) for 8 h, no changes in EVLWi, CO, and CBV were observed, and EVLWg was mean 4.39 g/kg body weight (BW). Five additional dogs were sacrificed after 15 min of anaesthesia without catheterization and EVLWg was found to be 4.24 g/kg BW. It is concluded that EVLWi does not change measurably during ZEEP or short periods of PEEP. However, long periods (8 h) of PEEP result in elevated EVLWi values. Gravimetry supports these conclusions.(ABSTRACT TRUNCATED AT 250 WORDS)


Exploring the unique function of imprinting control centers in the PWS/AS-responsible region: finding from array-based methylation analysis in cases with variously sized microdeletions.
Human 15q11-13 is responsible for Prader-Willi syndrome (PWS) and Angelman syndrome (AS) and includes several imprinted genes together with bipartite elements named AS-IC (imprinting center) and PWS-IC. These concertedly confer allele specificity on 15q11-13. Here, we report DNA methylation status of 15q11-13 and other autosomal imprinted differentially methylated regions (iDMRs) in cases with various deletions within the PWS/AS-responsible region. We performed array-based methylation analysis and examined the methylation status of CpG sites in 15q11-13 and in 71 iDMRs in six cases with various microdeletions, eight cases with conventional deletions within 15q11-13, and healthy controls. We detected 89 CpGs in 15q11-13 showing significant methylation changes in our cases. Of them, 14 CpGs in the SNORD116s cluster presented slight hypomethylation in the PWS cases and hypermethylation in the AS cases. No iDMRs at regions other than 15q11-13 showed abnormal methylation. We identified CpG sites and regions in which methylation status is regulated by AS-IC and PWS-IC. This result indicated that each IC had unique functions and coordinately regulated the DNA methylation of respective alleles. In addition, only aberrant methylation at iDMRs in 15q11-13 leads to the development of the phenotypes in our cases.


Hepatocyte growth factor/scatter factor activates the ETS1 transcription factor by a RAS-RAF-MEK-ERK signaling pathway.
Hepatocyte growth factor/scatter factor (HGF/SF) induces scattering and morphogenesis of epithelial cells through the activation of the MET tyrosine kinase receptor. Although the activated MET receptor recruits a number of signaling proteins, little is known of the downstream signaling pathways activated by HGF/SF. In this study, we wished to examine the signaling pathway leading to activation of the ETS1 transcription factor. Using in vitro and in vivo kinase assays, we found that HGF/SF activates the ERK1 MAP kinase, leading to the phosphorylation of the threonine 38 residue of ETS1 within a putative MAP kinase phosphorylation site (PLLT38P). This threonine residue was neither phosphorylated by JNK1, nor by p38 MAP kinases and was required for the induction of transcriptional activity of ETS1 by HGF/SF. Using kinase and transcription assays, we further demonstrated that phosphorylation and activation of ETS1 occurs downstream of a RAS-RAF-MEK-ERK pathway. The functional involvement of this pathway in HGF/SF action was demonstrated using U0126, a pharmacological inhibitor of MEK, which blocked phosphorylation and activation of ETS1, RAS-dependent transcriptional responses, cell scattering and morphogenesis. These data demonstrated that ETS1 is a downstream target of HGF/SF acting through a RAS-RAF-MEK-ERK pathway and provides a signaling pathway leading to the regulation of gene expression by HGF/SF.


Rapamycin targets STAT3 and impacts c-Myc to suppress tumor growth.
Rapamycin is widely recognized as an inhibitor of mTOR, and has been approved for clinical use as an immunosuppressant. Its potencies in anti-cancer, anti-aging, and neurodegenerative diseases are emergingly established. The exploration of other targets of rapamycin will further elucidate its underlying mechanisms of action. In this study, we use a chemical proteomics strategy that has identified STAT3, a transcription factor considered to be undruggable, as a direct functional protein target of rapamycin. Together with other multi-dimensional proteomics data, we show that rapamycin treatment in cell culture significantly inhibits c-Myc-regulated gene expression. Furthermore, we show that rapamycin suppresses tumor growth along with a decreased expression of STAT3 and c-Myc in an in vivo xenograft mouse model for hepatocellular carcinoma. Our data suggest that rapamycin acts directly on STAT3 to decrease its transcription activity, providing important information for the pharmacological and pharmaceutical development of STAT3 inhibitors for cancer therapy.


Malposition of a transvenous cardiac electrode associated with amaurosis fugax.
A 55-year-old male received a transvenous ventricular pacemaker for sick sinus syndrome. After pacemaker insertion, he developed recurrent episodes of amaurosis fugax. The source of thromboemboli was the pacemaker electrode malpositioned in the left ventricle. Position of the electrode was diagnosed correctly by two-dimensional echocardiography. The malpositioned electrode was successfully removed with cessation of recurrent thromboembolic phenomenon.


Isolated congenital absence of the nasal bones and aesthetic surgical correction: managing and case report.
A rare case of isolated congenital bone agenesis in a young woman referred to the authors for aesthetic correction of the dorsum profile is described. There are no descriptions of surgical treatment for this isolated facial defect in the literature. After a complete and accurate diagnostic study, a rhinoplasty was performed with a good result and without complications during a 2-year follow-up period. To explain this congenital malformation, several hypotheses were examined, such as bony resorption and embryologic bony development syndromes. This report describes the possibility of intervention in the case of nasal bone absence and shows how risks of structural instability can be avoided with an accurate preoperative study and a careful surgical approach.


Individual and population energetics of a lizard on a Mediterranean islet.
Population density in the lacertid lizardPodarcis lilfordi on the Mediterranean islet of Nitge, Menorca, Balearic Islands, was found to be 12 190 ind · ha-1 (SE, ±2135), exceeding densities reported for other island or mainland lizard populations. Field metabolic rates inP. lilfordi were measured by the doubly labeled water method, allowing estimation of a population metabolizable energy demand of 13.86 MJ · ha-1 · day-1-only 9.8% of that for a theoretical mammal population of the same body mass and density. Energy demand was considerably higher than that estimated for other lizard populations, primarily due to high population density but also because of high individual daily energy expenditure (1255 KJ · day-1; body mass=5.13 g). Field metabolic rates were partitioned into maintenance and activity components by respirometry of captive animals at field body temperatures. Activity metabolism formed the main component (77.4%) of total respiratory metabolism resulting from a combination of long daily activity periods (ca. 12 h), and greatly elevated metabolism during activity (5.7 times greater than resting levels). It is hypothesized that low food availability per individual constrains the time-energy budget of this species, obligating long periods of intense foraging.


Finding genes that influence quantitative traits with tree-based clustering.
We present a new statistical method to identify genes in which one or more variants influence quantitative traits. We use the Genetic Analysis Workshop 17 (GAW17) data set of unrelated individuals as a test of the method on the raw GAW17 phenotypes and on residuals after fitting linear models to individual-based covariates. By performing appropriate randomization tests, we found many significant results for a proportion of the genes that contain variants that directly contribute to disease but that have an increased type I error for analyses of raw phenotypes. Power calculations show that our methods have the ability to reliably identify a subset of the loci contributing to disease. When we applied our method to derived phenotypes, we removed many false positives, giving appropriate type I error rates at little cost to power. The correlation between genome-wide heterozygosity and the value of the trait Q1 appears to drive much of the type I error in this data set.


Enhancement of permeability in endothelial cells for the development of an antithrombogenic bioartificial hemofilter.
For the development of an antithrombogenic bioartificial hemofilter, in which the inner surface of hollow fibers is lined by endothelial cells, it is essential to increase the permeability of the cells in order to achieve a sufficient ultrafiltrate. We tried to increase it by using an actin microfilament polymerization inhibitor, cytochalasin B (CyB). Fifty microg/mL CyB was added for 2 h to the culture medium of confluent rat glomerular endothelial cells (RGEC) and human umbilical vein endothelial cells (HUVEC). Under the 130 mmHg hydrostatic pressure, the CyB-treated group produced significantly more ultrafiltration than the non-treated control group and this increase was maintained for at least 7 days. Horseradish peroxidase (HRP) permeability acutely and reversibly increased in the CyB-treated group compared with the non-treated control group. Scanning electron microscopy revealed a larger average diameter and increased number of fenestrae on the CyB-treated endothelial cells, compared with the non-treated cells. This phenomenon also lasted for at least 7 days. The platelet adherence test showed that CyB did not deteriorate the antithrombogenic property of endothelial cells. These results indicate that CyB is potentially applicable for the enhancement of endothelial cell permeability in an antithrombogenic bioartificial hemofilter.


Advantages of a selective beta-isoform phosphoinositide 3-kinase antagonist, an anti-thrombotic agent devoid of other cardiovascular actions in the rat.
Phosphoinositide 3-kinase (PI3K) beta has been shown to play a critical role in shear-induced arterial thrombosis. The anti-thrombotic effects of a beta isoform selective PI3K inhibitor, TGX221, were compared to the effects of non-selective PI3K inhibitors (LY294002 and wortmannin) and a PI3K delta inhibitor (IC87114) in the rat. TGX221 (2.5 mg/kg i.v.) abolished cyclic flow reductions in a Folts-like carotid artery stenosis preparation of thrombosis while not changing bleeding time, heart rate, blood pressure or carotid vascular conductance. In contrast, the PI3K non-selective isoform inhibitor, wortmannin (5 mg/kg i.v.) was as effective in abolishing cyclic flow reductions, but caused marked hypotension and carotid vasodilatation. In isolated mesenteric arteries, wortmannin was the most potent relaxant of K+-precontracted vessels (pEC(50)=6.6), while LY294002 and TGX221 were 40-60 fold less potent and IC87114 was without effect. These findings suggest that of the subclass of PI3K isoforms, the beta isoform is critical for the selective development of arterial thrombosis in vivo. The multiple actions of wortmannin are consistent with inhibition of the PI3K-C2alpha and beta isoforms and possibly other actions. Thus, a selective inhibitor of the beta isoform of PI3K offers advantages as a potential therapeutic target for the treatment of thrombosis without unwanted extension of bleeding time or adverse cardiovascular sequelae.


A priori prediction of local failure in brain metastasis after hypo-fractionated stereotactic radiotherapy using quantitative MRI and machine learning.
This study investigated the effectiveness of pre-treatment quantitative MRI and clinical features along with machine learning techniques to predict local failure in patients with brain metastasis treated with hypo-fractionated stereotactic radiation therapy (SRT). The predictive models were developed using the data from 100 patients (141 lesions) and evaluated on an independent test set with data from 20 patients (30 lesions). Quantitative MRI radiomic features were derived from the treatment-planning contrast-enhanced T1w and T2-FLAIR images. A multi-phase feature reduction and selection procedure was applied to construct an optimal quantitative MRI biomarker for predicting therapy outcome. The performance of standard clinical features in therapy outcome prediction was evaluated using a similar procedure. Survival analyses were conducted to compare the long-term outcome of the two patient cohorts (local control/failure) identified based on prediction at pre-treatment, and standard clinical criteria at last patient follow-up after SRT. The developed quantitative MRI biomarker consists of four features with two features quantifying heterogeneity in the edema region, one feature characterizing intra-tumour heterogeneity, and one feature describing tumour morphology. The predictive models with the radiomic and clinical feature sets yielded an AUC of 0.87 and 0.62, respectively on the independent test set. Incorporating radiomic features into the clinical predictive model improved the AUC of the model by up to 16%, relatively. A statistically significant difference was observed in survival of the two patient cohorts identified at pre-treatment using the radiomics-based predictive model, and at post-treatment using the the RANO-BM criteria. Results of this study revealed a good potential for quantitative MRI radiomic features at pre-treatment in predicting local failure in relatively large brain metastases undergoing SRT, and is a step forward towards a precision oncology paradigm for brain metastasis.


Regulation of cytosolic free calcium concentration by extracellular nucleotides in human hepatocytes.
The effects of extracellular ATP and other nucleotides on the cytosolic free Ca2+ concentration ([Ca2+]i) have been studied in single primary human hepatocytes and in human Hep G2 and HuH-7 hepatoma cells. ATP, adenosine 5'-O-(3-thiotriphosphate) (ATPgammaS), and UTP caused a concentration-dependent biphasic increase in [Ca2+]i with an initial peak followed by a small sustained plateau in most cells. In some cells, however, repetitive Ca2+ transients were observed. The rank order of potency was ATP >/= UTP > ATPgammaS, and complete cross-desensitization of the Ca2+ responses occurred between ATP and UTP. The initial transient peak in [Ca2+]i was resistant to extracellular Ca2+ depletion, which demonstrates mobilization of internal Ca2+ by inositol 1,4,5-trisphosphate whose formation was enhanced by ATP and UTP. In contrast, the sustained plateau phase required influx of external Ca2+. Ca2+ influx occurs most likely through a capacitative Ca2+ entry mechanism, which was shown to exist in these cells by experiments performed with thapsigargin. On the molecular level, specific mRNA coding for the human P2Y1, P2Y2, P2Y4, and P2Y6 receptors could be detected by RT-PCR in Hep G2 and HuH-7 cells. However, ADP and UDP, which are agonists for P2Y1 and P2Y6 receptors, respectively, caused no changes in [Ca2+]i, demonstrating that these receptors are not expressed at a functional level. Likewise, alpha,beta-methylene-ATP, beta,gamma-methylene-ATP, AMP, and adenosine were inactive in elevating [Ca2+]i, suggesting that the ATP-induced increase in [Ca2+]i was not caused by activation of P2X or P1 receptors. Thus, on the basis of the pharmacological profile of the nucleotide-induced Ca2+-responses, extracellular ATP and UTP increase [Ca2+]i by activating P2Y2 and possibly P2Y4 receptors coupled to the Ca2+-phosphatidylinositol signaling cascade in human hepatocytes. This suggests that extracellular nucleotides from various sources may contribute to the regulation of human liver cell functions.


Corrigendum: Effects of imidacloprid-induced hormesis on the development and reproduction of the rose-grain aphid Metopolophium dirhodum (Hemiptera: aphididae).
[This corrects the article DOI: 10.3389/fphys.2023.1113464.].


Intranasal granuloma faciale.
A 49-year-old man had a recurring intranasal mass accompanied by erythematous plaques on the forehead. Biopsy specimens of the skin and intranasal mass led to a diagnosis of granuloma faciale, a rare benign skin disorder. Lateral intranasal location and associated facial lesions help to clinically differentiate this lesion from more ominous midline granulomatous diseases. The lesions were treated with intralesional steroid injections. This may be the first reported intranasal occurrence of granuloma faciale.


Chromosomal changes in betel-associated oral squamous cell carcinomas and their relationship to clinical parameters.
To investigate the chromosomal imbalances that occur in oral carcinoma associated primarily with betel use and their clinical implications, we performed chromosomal analysis using comparative genomic hybridization on 47 patients with this disease. The most common gains of chromosome arms were 8q, 9q and 11q, and the most frequent losses were of chromosomal arms 3p and 4q. The clinical parameters significantly associated with the numbers of chromosomal imbalances per tumor were the age of the patients and nodal metastasis. The preliminary findings of a lower incidence of loss of 4q and gain of 8q in betel-associated tumors compared to non-betel-associated tumors might provide insight into the carcinogenic effect of betel. Deletion of 3p and the gain of 11q alterations were more prevalent in carcinomas with lymph node metastasis than in node-negative tumors, indicating possible loci for metastasis suppressor or metastasis enhancing genes, respectively. Losses of 3p and 4q and gain of 9q were associated with poor outcome for the patients. These data demonstrated that the frequent aberrations in 4q and 9q sites can be used as novel prognostic predictors.


Assessment of impacts to the sequence of the tropical cyclone Nisarga and monsoon events in shoreline changes and vegetation damage in the coastal zone of Maharashtra, India.
The tropical cyclones impact both the eastern and western coasts of India, causing severe socio-environmental problems. This study analyzed shoreline changes and vegetation degradation caused by cyclone Nisarga and monsoon events in Maharashtra coastal zone and Mumbai region, India. In this study, the shoreline change was studied using the Net Shoreline Movement (NSM) statistical technique embedded in the digital shoreline analysis system (DSAS) tool. The effects of the cyclone on the vegetation were mapped using the Normalized Difference Vegetation Index (NDVI), Enhanced Vegetation Index (EVI), and the rainfall distribution from Global Precipitation Measurement (GPM) data. The correlation between rainfall data and vegetation loss was analyzed using geographically weighted regression. The results also show that 90% of the events were concentrated in the 80-300 mm classes, being classified as sudden increases. This cyclone caused erosion in 56.32% of the shoreline; the highest erosion level was observed along the coastal zone of Maharashtra (near Mumbai city). Cyclone Nisarga has also impacted the vegetation loss most prominently in the region, with mean EVI in pre-cyclone equal to 0.4 and post-cyclone equal to 0.2. These eco-physical studies using geospatial technology are needed to understand the behavior of changes in shoreline and vegetation and can also help coastal managers plan for resilient coastal systems after the passage of tropical cyclones.


Morphologic analysis of macular neovascularizations by OCT angiography-Technical limitations in the comparison of 3×3mm and 6×6mm images.
The aim of this study was to ascertain whether there are relevant differences between the vascular morphology of macular neovascularizations (MNV) in 3×3mm and 6×6mm images, produced by optical coherence tomography angiography (OCTA). MNV of 49 patients were automated quantitative analysed, measuring area, flow, the fractal dimension, average vessel length, vascular density, and average vessel caliber. These parameters were compared between the 3×3mm and the 6×6mm images. A strong linear association was found between the 3×3mm and the 6×6mm images. While area, flow, and FD of the MNV were very similar, the 3×3mm images showed significantly lower average total vessel length, greater vascular density, and lower average vessel caliber. In quantitative analysis of the morphologic parameters of MNV in 3×3mm and 6×6mm images, the structures are not directly equivalent in the two sizes of scan. The images must be evaluated on an individual basis.


Comparative modulating effects of captopril, diltiazem, dietary calcium and pyridoxal-5'-phosphate on gentamicin-induced nephrotoxicity in the rat.
1. Nephrotoxicity was induced in rats by injecting gentamicin intramuscularly (i.m.) at a dose of 80 mg/kg/day for 6 days. Treated animals demonstrated a typical pattern of aminoglycoside nephrotoxicity characterized histopathologically by necrosis of proximal tubular epithelium, and biochemically by increased serum creatinine and urea concentrations. Reduced glutathione (GSH) concentration in renal cortex was significantly decreased by gentamicin. 2. Simultaneous treatment of rats with gentamicin and either captopril or diltiazem significantly potentiated the gentamicin-induced increases in serum creatinine and urea and did not significantly affect the gentamicin-induced decrease in cortical GSH concentration. 3. Concomitant treatment with gentamicin and either Ca2+ or pyridoxal-5'-phosphate decreased serum urea level, did not significantly affect serum creatinine concentration, and significantly increased cortical GSH concentration in comparison to the values of these parameters following gentamicin treatment. 4. Histopathologically, the severity of gentamicin-induced renal damage was exacerbated by captopril, and even more so by diltiazem. Simultaneous treatment with gentamicin and either Ca2+ or pyridoxal-5'-phosphate produced only mild focal atrophy of renal tubular epithelium. Control rats had apparently normal histology. 5. In conclusion, captopril and diltiazem, at the doses used, significantly potentiated gentamicin-induced nephrotoxicity to a broadly similar extent. Although Ca2+ and pyridoxal-5'-phosphate, at the doses used, reduced significantly the severity of some of the manifestations of nephrotoxicity, they were equally ineffective in completely preventing the development of nephrotoxicity.


Bis(O-ethyl dithio-carbonato-κS,S')bis-(pyridine-3-carbonitrile-κN)nickel(II).
The Ni(2+) ion in the title complex, [Ni(C(3)H(5)OS(2))(2)(C(6)H(4)N(2))(2)], is in a strongly distorted octa-hedral coordination environment formed by an N(2)S(4) donor set, with the Ni(2+) ion located on a centre of inversion. In the crystal, weak C-H⋯S and C-H⋯N inter-actions are observed.


Chicago classification criteria of esophageal motility disorders defined in high resolution esophageal pressure topography.
The Chicago Classification of esophageal motility was developed to facilitate the interpretation of clinical high resolution esophageal pressure topography (EPT) studies, concurrent with the widespread adoption of this technology into clinical practice. The Chicago Classification has been an evolutionary process, molded first by published evidence pertinent to the clinical interpretation of high resolution manometry (HRM) studies and secondarily by group experience when suitable evidence is lacking. This publication summarizes the state of our knowledge as of the most recent meeting of the International High Resolution Manometry Working Group in Ascona, Switzerland in April 2011. The prior iteration of the Chicago Classification was updated through a process of literature analysis and discussion. The major changes in this document from the prior iteration are largely attributable to research studies published since the prior iteration, in many cases research conducted in response to prior deliberations of the International High Resolution Manometry Working Group. The classification now includes criteria for subtyping achalasia, EGJ outflow obstruction, motility disorders not observed in normal subjects (Distal esophageal spasm, Hypercontractile esophagus, and Absent peristalsis), and statistically defined peristaltic abnormalities (Weak peristalsis, Frequent failed peristalsis, Rapid contractions with normal latency, and Hypertensive peristalsis). The Chicago Classification is an algorithmic scheme for diagnosis of esophageal motility disorders from clinical EPT studies. Moving forward, we anticipate continuing this process with increased emphasis placed on natural history studies and outcome data based on the classification.


Calculated absorption and vibrational circular dichroism spectra of fundamental and overtone transitions for a chiral HCCH molecular fragment in the hypothesis of coupled dipoles.
We establish the general behavior of absorption and vibrational circular dichroism spectra (VCD) of a chiral HCCH fragment lacking all symmetry elements; the study is limited to CH-stretching modes, and the Hamiltonian employed is written in terms of normal-mode coordinates and momenta and approximates two different Morse oscillators interacting through a harmonic coupling term; rotational strengths are evaluated within a hypothesis of coupled electric dipoles. Van Vleck contact transformations written in terms of raising and lowering operators are used to calculate spectra up to the manifold Deltav = 4. Three transformations are necessary to obtain fourth-order terms in the relevant operators, namely, the electric and magnetic dipole moments. The dynamics of the system exhibits 1:1 resonance terms in addition to the Darling-Dennison coupling term. We discuss the importance of coupling between CH stretches with respect to differences in their local mechanical characteristics in determining the aspect of the absorption and VCD fundamental and overtone spectra of increasing quantum number.


Comparison of bacteriophage typing, serotyping, and biotyping as aids in epidemiological surveillance of Klebsiella infections.
Bacteriophage typing was used to subdivide Klebsiella obtained from patients in a surgical intensive care unit during a 2-year period. The 15 phages employed to type the strains were propagated by a soft-agar layer technique. In all, 23 phage types were found among the 120 clinical strains. The phage types of repeat isolates were reproducible. Only 70% of the strains tested were phage typable, but when used in conjunction with capsular serotyping and biotyping, a much greater subdivision of the Klebsiella strains was achieved. The addition of phage typing to serobiotyping for epidemiological analysis suggested that the number of cross-infecting Klebsiella strains in the intensive care unit was few, but that these strains persisted in the unit for long periods of time and could infect different body sites.


Adoptive transfer of immunity against solid fibrosarcoma in mice with splenocytes and peritoneal exudate cells obtained after in vitro sensitization and in vivo immunization with cis-dichlorodiamine platinum(II) treated fibrosarcoma cells.
Co-cultivation of splenocytes with cis-dichlorodiamine platinum (II) treated tumor cells generate cytotoxic splenocytes, which when injected into normal mice, render them resistant to tumor challenge. Significant increases in mean survival time and 33% of tumor free survivals were observed in mice exposed to a tumor challenge on the 10th day after injection of sensitized splenocytes. Splenocytes peritoneal exudate cells obtained after in vivo immunization of mice with cis-dichlorodiamine platinum(II) treated cells retarded tumor growth in vivo when injected in different combinations in tumor bearing mice. Maximum survival time of tumor bearing mice and 20% tumor free survivals were observed when the animals were injected with a combination of immune splenocytes and normal peritoneal exudate cells. The increase in the number of macrophages of immunotherapeutically treated mice suggests that host macrophages have been activated. Splenocytes and macrophages obtained from immunotherapeutically treated mice showed an increase in cytotoxicity against tumor cells in vitro.


Ulysses transposable element of Drosophila shows high structural similarities to functional domains of retroviruses.
We have determined the DNA structure of the Ulysses transposable element of Drosophila virilis and found that this transposon is 10,653 bp and is flanked by two unusually large direct repeats 2136 bp long. Ulysses shows the characteristic organization of LTR-containing retrotransposons, with matrix and capsid protein domains encoded in the first open reading frame. In addition, Ulysses contains protease, reverse transcriptase, RNase H and integrase domains encoded in the second open reading frame. Ulysses lacks a third open reading frame present in some retrotransposons that could encode an env-like protein. A dendrogram analysis based on multiple alignments of the protease, reverse transcriptase, RNase H, integrase and tRNA primer binding site of all known Drosophila LTR-containing retrotransposon sequences establishes a phylogenetic relationship of Ulysses to other retrotransposons and suggests that Ulysses belongs to a new family of this type of elements.


Weaning from ventilation in paediatric intensive care: an intervention study.
To standardise the paediatric intensive care unit (PICU) team's approach to weaning paediatric patients from mechanical ventilation. The study employed a time series design over 2 years. A total of 220 patients (pre-intervention n=107 and post-intervention n=113) were studied. Independent variables measured in both the pre- and post-intervention groups included total ventilation time (TVT), weaning duration (WD), and length of stay (LOS), as well as quality indicators (weaning failure and reintubation rates). The pre-intervention analysis demonstrated an existing fluctuation between outcome variables. When outcome indicators were compared between the pre- and post-intervention groups, both TVT and LOS were longer post-intervention (median difference: TVT -15.8 hours, P<0.068; and LOS -23.75 hours, P<0.088). WD was comparable between groups (median difference: WD -1.5 hours, P<0.427). Quality indicators were better post-intervention. Kaplan-Meier survival analysis demonstrated that long-term ventilated patients post-intervention had a reduced probability of remaining ventilated. Weaning children from mechanical ventilation can be performed safely and effectively with the aid of collaborative guidelines. Although times were prolonged, the quality indicators were slightly improved, indicating that quicker was not always better. Long-term ventilated patients, in particular, would appear to benefit from weaning guidelines.


Mobile reminders to improve opportunistic screening of type 2 diabetes mellitus: Data documentation and data analysis plan of a randomized trial data.
This Data in Brief article contains individual level data of a randomized trial in a primary care setting. This trial offered mobile reminder to follow up for definitive tests during opportunistic screening of diabetes mellitus in Puducherry, India (2014). ("Effect of mobile reminders on screening yield during opportunistic screening for type 2 diabetes mellitus in a primary health care setting: a randomized trial" (Kumar et al., 2015) [1]) Variables collected included the baseline characteristics of study participants (n=390) and information on initial screening and eligibility for definitive test, study group (intervention/control), follow up for definitive test and definitive test results. The data was double entered with adequate checks and validated in EpiData. Final data after correcting the data entry errors has been shared here. In addition, we have shared data entry plan, EpiData triplet files for data entry and program file for data analysis. They may be used by other researchers who intend to replicate this research in their setting.


Synthesis of nature product kinsenoside analogues with anti-inflammatory activity.
Kinsenoside is the major bioactive component from herbal medicine with a broad range of pharmacological functions. Goodyeroside A, an epimer of kinsenoside, remains less explored. In this report we chemically synthesized kinsenoside, goodyeroside A and their analogues with glycan variation, chirality inversion at chiral center(s), and bioisosteric replacement of lactone with lactam. Among these compounds, goodyeroside A and its mannosyl counterpart demonstrated superior anti-inflammatory efficacy. Furthermore, goodyeroside A was found to suppresses inflammatory through inhibiting NF-κB signal pathway, effectively. Structure-activity relationship is also explored for further development of more promising kinsenoside analogues as drug candidates.


The use of computed tomography and ultrasonography in the evaluation of orbital masses.
The combined use of computed tomography scans with multiplanar reformation and ultrasonography makes it possible to locate orbital masses with a high degree of accuracy, and sometimes even to determine their histological nature without surgical biopsy. One of the unique features of computed tomography is its ability to distinguish both normal and abnormal structures of various tissue densities; this has contributed to very low false positive and false negative rates. Ultrasonography, while of limited use in the detection of posterior orbital lesions or lesions involving the orbital bones, provides an excellent cost-effective screening test for anterior and midorbit disease. It is also useful for the detection of extraocular muscle enlargement secondary to thyroid disease. In this article, a review of the characteristics and techniques of computed tomography and ultrasonography is followed by discussion of the advantages and limitations of each modality in the evaluation of six common types of orbital tumefaction.


Clinical pharmacology of antihypertensive therapy.
Adequate control of blood pressure poses challenges for hypertensive patients and their physicians. Success rates of greater than 80% in reducing blood pressure to target values among high-risk hypertensive patients reported by several recent clinical trials argue that effective medications currently are available. Yet, only 34% of hypertensive patients in the United States are at their goal blood pressure according to the most recent national survey. Rational selection of antihypertensive drugs that target both the patient's blood pressure and comorbid conditions coupled with more frequent use of low-dose drug combinations that have additive efficacy and low adverse-effect profiles could improve significantly US blood pressure control rates and have a positive impact on hypertension-related cardiovascular and renal mortality and morbidity. This article reviews the pharmacokinetic and pharmacodynamic principles that underlie the actions of drugs in each of the classes of antihypertensive agents when used alone and in combination, provides practical pharmacologic information about the drugs most frequently prescribed for treatment of hypertension in the outpatient setting, and summarizes the current data influencing the selection of drugs that might be used most effectively in combination for the majority of hypertensive patients whose blood pressures are not controlled adequately by single-drug therapy.


A procedure for detecting changes in the internal Ca2+ concentration in isolated nerve endings using the metallochromic dye arsenazo III.
A method for detecting changes in the internal concentration of Ca2+ in synaptosomes from mouse brain is described. Synaptosomes were fused with phosphatidylcholine-phosphatidylserine unilamellar liposomes previously loaded with the metalochromic, Ca2+ -sensitive dye arsenazo III, in order to introduce the dye into the synaptosomes. The fusion was promoted by La3+. Changes in the differential absorption between 660 and 690 nm, which indicate changes in Ca2+ concentration, were followed in a double beam spectrophotometer. It was found that both in the dye-loaded liposomes and in the fused synaptosomes, the addition of the Ca2+ ionophore A23187 to the medium containing Ca2+ produced a notable change in the differential absorbance 660-690 nm. When the depolarizing alkaloid veratridine was added, there was no response in the liposomes, whereas a change in the differential absorbance 660-690 nm was detected in the fused synaptosomes containing arsenazo but only when Na+ was present in the medium. These fused synaptosomes were able to release labeled gamma-aminobutyric acid as a response to veratridine, in a Na+ -dependent manner, similarly to control non-fused synaptosomes. These results demonstrate the feasibility of fusion to introduce Ca2+ -sensitive dyes into isolated nerve endings from the mammalian brain and therefore to detect changes in their internal Ca2+ concentration.


DAFA-BiLSTM: Deep Autoregression Feature Augmented Bidirectional LSTM network for time series prediction.
Time series forecasting models that use the past information of exogenous or endogenous sequences to forecast future series play an important role in the real world because most real-world time series datasets are rich in time-dependent information. Most conventional prediction models for time series datasets are time-consuming and fraught with complex limitations because they usually fail to adequately exploit the latent spatial dependence between pairs of variables. As a successful variant of recurrent neural networks, the long short-term memory network (LSTM) has been demonstrated to have stronger nonlinear dynamics to store sequential data than traditional machine learning models. Nevertheless, the common shallow LSTM architecture has limited capacity to fully extract the transient characteristics of long interval sequential datasets. In this study, a novel deep autoregression feature augmented bidirectional LSTM network (DAFA-BiLSTM) is proposed as a new deep BiLSTM architecture for time series prediction. Initially, the input vectors are fed into a vector autoregression (VA) transformation module to represent the time-delayed linear and nonlinear properties of the input signals in an unsupervised way. Then, the learned nonlinear combination vectors of VA are progressively fed into different layers of BiLSTM and the output of the previous BiLSTM module is also concatenated with the time-delayed linear vectors of the VA as an augmented feature to form new additional input signals for the next adjacent BiLSTM layer. Extensive real-world time series applications are addressed to demonstrate the superiority and robustness of the proposed DAFA-BiLSTM. Comparative experimental results and statistical analysis show that the proposed DAFA-BiLSTM has good adaptive performance as well as robustness even in noisy environment.


Effectiveness of supervised physiotherapy after arthroscopic rotator cuff reconstruction: a randomized controlled trial.
The benefit of supervised physiotherapy after rotator cuff surgery is unclear. The aim of this randomized controlled trial was to assess the effectiveness of supervised physiotherapy after arthroscopic rotator cuff reconstruction. Eighty patients with full-thickness supraspinatus tendon tears were randomly assigned to either supervised physiotherapy or home exercises only. The primary outcome measure was the Constant score at 12 months after surgery. A total of 70 patients were available for analyses at 1-year follow-up. There were no statistically significant differences in the primary outcome between the treatment groups. Supervised physiotherapy after arthroscopic rotator cuff reconstruction does not provide additional benefit compared with home exercises alone at 1-year follow-up.


Extrusive luxation. Therapeutic procedure.
Repositioning a traumatized tooth involves replacing and stabilizing it. When it is not possible, a method has been developed by an acetate splint. After few weeks, the tooth was aligned and correctly positioned. Repositioning a traumatized tooth involves, first, replacing and second stabilizing it. Stabilization, on the other hand, usually requires flexible splints. Occasionally the immediate replacement may be impossible being necessary to use other procedure. When complete replacement is not possible.


Truke, a web tool to check for and handle excel misidentified gene symbols.
Genomic datasets accompanying scientific publications show a surprisingly high rate of gene name corruption. This error is generated when files and tables are imported into Microsoft Excel and certain gene symbols are automatically converted into dates. We have developed Truke, a fexible Web tool to detect, tag and fix, if possible, such misconversions. Aside, Truke is language and regional locale-aware, providing file format customization (decimal symbol, field sepator, etc.) following user's preferences. Truke is a data format conversion tool with a unique corrupted gene symbol detection utility. Truke is freely available without registration at http://maplab.cat/truke .


Intra-habenular injection of 6-hydroxydopamine produces impaired acquisition of DRL operant behavior.
The anatomical connections of the habenula complex indicate it provides a relay between limbic forebrain and midbrain. Somewhat paradoxically, consequences of nonspecific lesion of the habenula are ambiguous with little change in basic response evident within simple behavioral paradigms. However, the potential functional importance for this relay has more recently been indicated by the demonstration of deficits in the ability of lesioned animals to alter behavior appropriate to both internal and external stimuli in more demanding behavioral tasks. Doubts concerning the importance of the habenula remain because of the large number of descending fibers of passage through the habenula. To provide more substantive evidence, 6-hydroxydopamine was injected into the habenula of rats to provide more limited lesion of catecholaminergic terminals. Animals were subsequently trained on an operant DRL 20-s schedule for which deficits have been reported following nonspecific lesion of the habenula. Lesioned animals showed a tendency to overrespond and were significantly less efficient on the schedule with decreased number of reinforcements received relative to controls. While the neurotoxic lesion procedure used does not differentiate noradrenergic and dopaminergic damage, the importance of intact catecholaminergic systems within the habenula for effective DRL acquisition is consistent with the suggested importance of the habenula for feedback regulation of dopamine within the ventral tegmental area through ascending dopamine fibers to the habenula.


Temperature influence on mobilisation and (re)fixation of trace elements and heavy metals in column tests with aquifer sediments from 10 to 70 °C.
The operation of seasonal underground thermal energy storages (UTES) as part of renewed heat supply systems can cause amplified temperature variations in the urban subsurface. Therefore, long-term environmental consequences for water extractions by trace elements and heavy metals (TEHMs) are a key point of concern regarding temperature effects on aquifer hydrogeochemistry. To address this issue, we report the results of flow-through and circular-flow column tests conducted with 4 anoxic northern German aquifer sediments, tempered to 10, 25, 40 and 70 °C and analysed for 20 TEHMs. Increased temperatures in column tests caused increasing Li, As, Mo, Sb and Ba concentrations and decreasing Ni concentrations in all of the sediments with a sediment-specific extent, whereas effects on V, Mn, Co, Tl and U concentrations varied sediment-specifically. Apart from Ba, all these components were released as a pulse in the initial heating phase, indicating a temperature dependent, finite, elutable pool. Re-cooling of the previously heated circular-flow column tests to 10 °C caused reversals of concentration changes by 30-95%. This indicates a return to initial hydrochemical conditions after termination of heat storage operation and downstream from heat storages during the operations. The latter was approximated for As with a simplified analytical 1-dimensional approach, presuming transferability from a laboratory to a field scale. This reversal in concentration changes enables active cooling as a countermeasure in cases of unexpected, adverse TEHM progression. From the perspective of our findings, TEHM concentration changes appear to be temporally and spatially limited.


Association of HLA-DR/DQ polymorphism with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) in Tunisian patients.
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune-mediated disorder of the peripheral nervous system (PNS). The aim of this study was to investigate associations between HLA-DR/DQ alleles and CIDP in Tunisian patients. HLA DR/DQ genotyping was performed using polymerase chain reaction sequence-specific primers (PCR-SSP) with 36 CIDP patients and 100 healthy individuals serving as the control group. CIDP in Tunisian patients was found to be associated with the HLA-DRB1*13 allele (pc=0.03) (where pc denotes the Bonferroni corrected probability value). Moreover, the two haplotypes, DRB1*13/DQB1*06 (22.22% of patients vs. 8.5% of controls, pc=0.017) and DRB1*07/DQB1*03 (13.88% of patients vs. 3% of controls, pc=0.005), were found to confer a susceptibility to CIDP. To our knowledge, this is the first study performed to analyze the association of HLA-DRB1/DQB1 alleles on CIDP susceptibility in a Tunisian population.


Polyclonal antibody production induced by parotid protein and its active glycopeptide in mouse and human lymphocytes.
Parotid protein (extracted from bovine parotid gland), one parotid subunit, and the active fragment (FrAA-1) induced polyclonal IgM, IgG, and IgA antibody production in murine spleen cells in vivo and in vitro. The parotid subunit also elicited polyclonal IgM antibody responses in immune defective CBA/N and LPS nonresponder C3H/HeJ mouse. When one carbohydrate residue in the subunit was removed by treatment with mixed galactosidase, the ability to generate nonspecific responses was markedly reduced. In human peripheral lymphocytes, the parotid subunit and FrAA-1 induced considerable polyclonal IgM antibody production. The subunit was not toxic to human lymphocytes. Therefore, it seems possible that parotid protein could be applied to immunopharmacological therapy for conditions such as immunodeficiency.


Routine HIV testing in acute medical admissions in a high prevalence area reduces morbidity and mortality of HIV: a full cycle audit.
Late HIV diagnosis in the UK remains a major cause of morbidity and mortality. In line with British HIV Association recommendations, we implemented routine HIV Screening in Croydon University Hospital Acute Medical Unit in London after an audit in 2011 revealed very high levels of late diagnosis. Our re-audit assessed the impact of Acute Medical Unit screening and found that patients identified by screening, compared to those tested due to clinical suspicion of HIV, were significantly less likely to be diagnosed late, had fewer AIDS-defining illnesses and shorter hospital admissions. In addition, screening identified patients who were not in traditional 'high-risk' groups and patients who had defaulted HIV care and who subsequently re-engaged with care.


Experiment in an early admissions program at the University of Utah College of Medicine.
Thirty-one selected high school graduates were accepted into the College of Medicine prior to any college course work. The program was established to provide greater educational opportunity to the gifted student.


Regressing atypical histiocytosis, a regressing cutaneous phase of Ki-1-positive anaplastic large cell lymphoma. Immunocytochemical, nucleic acid, and cytogenetic studies of a new case in view of current opinion.
Regressing atypical histiocytosis is a rare multifocal cutaneous tumor characterized by large, spontaneously regressing, ulcerating skin nodules. Although initially self-remitting, the condition may progress to systemic lymphoma. Using material from one patient, an attempt was made to clarify the nature of this condition with immunophenotyping, genotyping, and chromosome studies. Immunophenotyping studies indicated the condition was of T-cell lineage, although T-cell receptor gene studies showed polyclonal rearrangement. This case progressed to systemic lymphoma. The authors believe regressing atypical histiocytosis is a regressing phase of Ki-1-positive anaplastic large cell lymphoma of the skin.


An update on therapeutic uses of radiotracers in neoplastic disease.
The key to delivering radiation to a lesion by means of internally administered radiopharmaceuticals is specificity of localization (a high lesion-background ratio). Factors that may limit this localization are pointed out. Potential alteration of the residence time within the lesion and use of radiation-sensitizing agents may bring new applications for radionuclides in therapy. The most common therapeutic applications of radiopharmaceuticals are outlined.


Brachytherapy of stage II mobile tongue carcinoma. Prediction of local control and QOL.
There is no consensus as to the prognostic model for brachytherapy of tongue carcinoma. This study was designed to evaluate the prognostic factors for local control based on a large population under a unified treatment policy. Between 1970 and 1998, 433 patients with stage II tongue squamous cell carcinoma were treated by low-dose-rate brachytherapy. This series included 277 patients treated with a linear source with a minimum follow-up of 3 years. A spacer was introduced in 1987. The primary local control rates were 85.6%. In the multivariate analysis, an invasive growth pattern was a significant factor for local recurrence. The disease-related survival was influenced by old age and an invasive growth pattern. A spacer lowered mandibular bone complications. The growth pattern was the most important factor for recurrence. Brachytherapy was associated with a high cure rate and the use of spacers brought about good quality of life (QOL).


Development of a Loop Mediated Isothermal Amplification (LAMP) - Surface Enhanced Raman spectroscopy (SERS) Assay for the Detection of Salmonella Enterica Serotype Enteritidis.
As a major foodborne pathogen, Salmonella enterica serotype Enteritidis is increasingly rising as a global health concern. Here, we developed an integrated assay that combines loop mediated isothermal amplification (LAMP) and surface enhanced Raman spectroscopy (SERS) for DNA detection of S. Enteritidis using specifically designed Raman active Au-nanoprobes. The target DNA was amplified by LAMP and then labeled with Au-nanoprobes comprised of gold nanoparticle-modified with specific cy5/DNA probes to allow the detection by SERS. The sensitivity of the developed LAMP-SERS detection assay (66 CFU/mL) was ~100-fold higher than the conventional polymerase chain reaction (PCR) method. Significantly, this technique allowed highly specific detection of the target DNA of S. Enteritidis and could differentiate it from the DNA of closely related bacterial species or non-specific contamination, making it more accurate and reliable than the standard LAMP technique. The applicability of detection of S. Enteritidis in milk samples using LAMP-SERS assay was validated as well. In sum, the developed LAMP-SERS assay is highly specific and sensitive, and has the potential to be applied for rapid detection of different foodborne pathogens and other microbial contaminants.


Inadequacy of conventional computerized tomography scans for treatment planning of tangential breast (chest wall) fields.
The use of transverse tomography treatment-planning scans, which have to be taken in the exact treatment position of the patients, is essential for precision radiotherapy of breast cancer. Transverse tomography scans give all necessary informations for an optimal isodose distribution within the target volume for the individual patient, and maximal sparing of normal tissues (e.g. lung) is achieved. The exact topography of internal mammary nodes may also be incorporated in the planning scan with the help of lymphoscintigraphy. Conventional computerized tomography (CT) scanners have too small gantry openings (50-70 cm) to allow for proper positioning of the patients under treatment conditions. Using such treatment-planning scans for patients in the actual treatment position would cause an underdosage in excess of 5% within the target volume, when 60Co fields are used. Also, a much larger volume of normal tissues (mainly lung) would unnecessarily be irradiated. Treatment-planning scans obtained by TAT (transverse analog tomography) do not have the crucial positioning problems of conventional CT scanners and enable the precise transformation of a valid isodose distribution to each patient. In addition, positioning wedges (with adjustable wedge angles) may be placed under the patient to achieve the optimal treatment position. A useful alternative of TAT scanning for precise treatment planning of patients with breast cancer would be a CT scanner with a wide enough gantry opening to allow for any patient positioning under actual treatment conditions.


Inducible Prrxl1-CreER(T2) recombination activity in the somatosensory afferent pathway.
Prrxl1-CreER(T2) transgenic mice expressing tamoxifen-inducible Cre recombinase were generated by modifying a Prrxl1-containing BAC clone. Cre recombination activity was examined in Prrxl1-CreER(T2); Rosa26 reporter mice at various embryonic and postnatal stages. Pregnant mice were treated with a single dose of tamoxifen at embryonic day (E) 9.5 or E12.5, and X-gal staining was performed 2 days later. Strong X-gal staining was observed in the somatosensory ganglia (e.g., dorsal root and trigeminal ganglia) and the first central sites for processing somatosensory information (e.g., spinal dorsal horn and trigeminal nerve-associated nuclei). When tamoxifen was administered at postnatal day (P) 20 or in adulthood (P120), strong Cre recombination activity was present in the primary somatosensory ganglia, while weak Cre recombination activity was found in the spinal dorsal horn, mesencephalic trigeminal nucleus, principal sensory trigeminal nucleus, and spinal trigeminal nucleus. This mouse line provides a useful tool for exploring genes' functions in the somatosensory system in a time-controlled way.


Pediatric Rhabdomyosarcoma in India: A Single-center Experience.
Analyze the profile and outcome of children with rhabdomyosarcoma from a pediatric-oncology unit. Retrospective analysis of case records over 23 years (1990-2012). Government-run, tertiary-care, university hospital in Northern India. 159 children (<12-years) with a diagnosis of rhabdomyosarcoma were enrolled. The median age was 4 years; 13% were infants. Five-year event free survival. The median symptom interval was 2-months. Head and neck region was the most frequent site (44%), followed by tumors in the extremity (15.7%). The majority (67%) of the tumors were located at 'unfavorable' sites; 68% were >5 cm in size. The most frequent (58%) pathological subtype was embryonal. Treatment was based on the 'Intergroup Rhabdomyosarcoma Study (IRS) Group' risk-stratification. 33% were 'low-risk' children, 11% were 'high-risk'. Treatment-refusal (18%) and abandonment (33%) were major impediments. The median ± SE five-year event free survival of those taking treatment was 43.6 ± 6%. Large sized tumors, tumors at unfavorable locations, and treatment refusal/abandonment contributed to inferior outcome in children with rhabdomyosarcoma.


Effects of Sacubitril/Valsartan on biomarkers of fibrosis and inflammation in patients with heart failure with reduced ejection fraction.
To evaluate the circulating levels of remodeling biomarkers procollagen type 1 C-terminal propeptide (PICP), human cartilage glycoprotein-39 (YKL-40), plasma renin activity (PRA), aldosterone (Aldo) as well as clinical and echocardiographic parameters in patients with heart failure with reduced ejection fraction (HFrEF), before and after treatment with Sacubitril/Valsartan (S/V). A total of 26 consecutive patients with HFrEF on stable clinical conditions were studied. Clinical, echocardiographic parameters and circulating biomarkers were measured at baseline, after 30 and 60 days of S/V treatment. Both systolic blood pressure (SBP) and diastolic blood pressure (DBP) decreased, from 126 ± 15 to 113 ± 4 mmHg (p < 0.001) and from 77 ± 11 to 72 ± 9 mmHg (p = 0.005), respectively, at the end of study. Concomitantly, left ventricular ejection fraction (LVEF) increased by 22.8% from 29.5 ± 5% to 36.2 ± 5%, (p < 0.001) and indexed left ventricular end-systolic volume (LVESVi) decreased by 12% from 38.6 ± 8.7 ml/m2 to 34.0 ± 10.0 ml/m2. (p = 0.007). Circulating levels of PICP, YKL-40, PRA and Aldo decreased by - 42.2%, - 46.8%, - 79.1% and - 76.7%, respectively (p < 0.001 for all), the decrements being already maximal within 30 days of S/V treatment. No significant changes of plasma electrolytes and creatinine were observed during the study (all p > 0.05). A decrease of circulating markers of inflammation and fibrosis during chronic treatment with S/V is associated with an improvement of hemodynamic and echographic parameters in patients with HRrEF. These data are compatible with an anti-fibrotic and anti-inflammatory effect of S/V, that may contribute to the beneficial outcomes of the drug in this clinical setting.


A study of the interaction of practolol with acetylcholine, histamine, serotonin and bradykinin in the guinea-pig, and with bean-sprout juice in the mouse.
1. The interactions of practolol with acetylcholine, histamine, serotonin and bradykinin were studied on the trachea and lung of the guinea-pig, an animal whose sensitivity to bronchoactive endogens is known to be similar to that of human asthmatic bronchi. 2. Practolol, like propranolol, potentiated the action of the first three agonists mentioned above, but, unlike propranolol, it did not potentiate the bronchospastic effect of bradykinin. 3. Practolol, in fact, antagonized the action of bradykinin, but this effect was unlike that produced by nonsteroidal anti-inflammatory drugs. 4. The possibility that beta-adrenoreceptor antagonists might show adverse interactions with certain foodstuffs was investigated, an is discussed. 5. It is suggested that the feasibility of the continued use of practolol (or the newer cardioselective beta-blockers) in asthmatics necessarily depends on the type of allergic reaction involved, and so it is not possible to generalize. Any drug or food that might cause a bronchospastic effect synergistically in the presence of a beta- adrenoreceptor antagonist, even a cardioselective one, should be regarded with suspicion.


Further support for the families of Australia's war veterans requires a broad research strategy.
Vietnam veterans reported a high prevalence of health problems among their partners and children in a 1998 survey. Data about the effect of our veterans' war service on the health of their families are quite limited. These data are mainly from the Vietnam and Gulf Wars; cover veterans, partners and children independently; and largely focus on the individuals' medical conditions and risk factors. Australia should develop a broad research strategy that uses a wider definition of health, looks at veterans' families as a whole, and does so from a range of perspectives, including sociological, life-course and trans-generation perspectives. Preventive research should be emphasised, especially into enhancing resilience of veterans' families. The use and usefulness of current services should be evaluated, including whether they need to be more family-inclusive.


Genomic leftovers: identifying novel microsatellites, over-represented motifs and functional elements in the human genome.
The human genome is 99% complete. This study contributes to filling the 1% gap by enriching previously unknown repeat regions called microsatellites (MST). We devised a Global MST Enrichment (GME) kit to enrich and nextgen sequence 2 colorectal cell lines and 16 normal human samples to illustrate its utility in identifying contigs from reads that do not map to the genome reference. The analysis of these samples yielded 790 novel extra-referential concordant contigs that are observed in more than one sample. We searched for evidence of functional elements in the concordant contigs in two ways: (1) BLAST-ing each contig against normal RNA-Seq samples, (2) Checking for predicted functional elements using GlimmerHMM. Of the 790 concordant contigs, 37 had an exact match to at least one RNA-Seq read; 15 aligned to more than 100 RNA-Seq reads. Of the 249 concordant contigs predicted by GlimmerHMM to have functional elements, 6 had at least one exact RNA-Seq match. BLAST-ing these novel contigs against all publically available sequences confirmed that they were found in human and chimpanzee BAC and FOSMID clones sequenced as part of the original human genome project. These extra-referential contigs predominantly contained pentameric repeats, especially two motifs: AATGG and GTGGA.


Characterization and functional recovery of a novel antimicrobial peptide (CECdir-CECret) from inclusion bodies after expression in Escherichia coli.
CECdir-CECret is a novel non-toxic doublet 8.5 kDa peptide representing the natural coding sequence of the antimicrobial peptide Cecropin A from Drosophila melanogaster fused in-frame to its own inverted version. Expression of this cloned doublet peptide in Escherichia coli, yielded peptides that were mostly packaged into inclusion bodies. The new molecule was purified, solubilized and refolded, through a standard guanidine-based procedure. The recovered refolded peptides were then characterized by HPLC chromatography, MALDI-TOF-mass spectrometry and peptide sequencing, and finally evaluated for their antimicrobial potential. The novel doublet peptide CECdir-CECret, displays an enhanced in vitro antimicrobial activity and action spectrum in comparison to the monomer Cecropin A.


[Planning of working conditions and tasks in creating optimal standards of technology in coal mines].
During the next 20 years normalization of occupational factors at Donbas mines should be ensured by technical reconstruction of mines on the basis of the development of new technological circuits, automatization and mechanization means, the means of collective protection, physiologic labour rationalization.


Surgical infrarenal "neo-neck" technique during elective conversion after EVAR with suprarenal fixation.
Conversion of a previous endovascular aneurysm repair (EVAR) with suprarenal fixation is a challenging situation even in the elective setting. The outcomes of a technique based on preservation of the first proximal covered stent of the endograft, used as a "neo-neck" for proximal anastomosis, are presented. From 2001 to 2014, nine patients underwent elective conversion of a previous suprarenally fixed EVAR. After supraceliac clamping, the aneurysm sac was opened and the endograft identified; the fabric was cut beyond the first covered stent together with its native aortic wall in order to create a "neo-neck." An aortic balloon was inflated into the visceral aorta to avoid back bleeding. A Dacron bifurcated tube graft (Intergard, Maquet) was then sutured to the neo-neck mimicking endobanding, passing the stitches into the aortic wall and the first covered stent. The mean age was 68 years (range, 52-84 years). The stent grafts removed were four Zenith (Cook Medical), three Endurant (Medtronic), and two E-vita (Jotec). The indication for conversion was type 1A (n = 2), type 2 (n = 2), and type 3 (n = 1) endoleak, complete endograft thrombosis (n = 2), and abdominal pain with sac enlargement with no radiological sign of endoleak (n = 2). Blood loss was 1,428 mL (range 500-3,000 mL); the visceral ischemic time to perform the proximal anastomosis was 23.5 min ± 2.3 min). The post-operative complication rate was 11% (n = 1/9) related to a case of sac wall bleeding requiring re-intervention; mortality at 30 days was 0%. At 22 months (range, 8-41) the computed tomography angiogram demonstrated no signs of leaks or anastomotic pseudoaneurysm. Preservation of the proximal covered stent of an endograft with suprarenal fixation used as an infrarenal "neo-neck" with incorporation of the aorta to the suture line during elective surgical explantation simplifies the procedure, and can be achieved with very low early morbidity and mortality; furthermore, it seems to be durable over mid-term follow up.


K+ and Ca2+ modified Na-X zeolites as possible bile acids sequestrant.
Modified zeolite X, previously exchanged with K+ and Ca2+ cations were characterized by XRD, FT-IR, chemical analysis and BET techniques. Different masses of these solids were mixed with an ox bile solution at different reaction times. The supernatants obtained by centrifugations were submitted to bile acid and phospholipids quantitative determinations. The amount of bile acids adsorbed was 65, 28 and 77% and for phospholipids was 45, 67 and 98% for KX, NaX and CaX respectively. As expected, as the amount of mass used increases more bile acids and phospholipids are adsorbed due to a larger surface of the solid being available for adsorption. On the other hand, 120 min of reaction time were sufficient for the adsorption of both components. The solids, after incubations with bile solutions were treated with abundant distilled water and dried at room temperature. The FT-IR analysis of these solids did not detect any bile and on the zeolite surface with suggested that the bile acid adsorption on the exchanged zeolites is moderated by weak and non covalent interactions.


Methodology for the development of a Canadian national EMS research agenda.
Many health care disciplines use evidence-based decision making to improve patient care and system performance. While the amount and quality of emergency medical services (EMS) research in Canada has increased over the past two decades, there has not been a unified national plan to enable research, ensure efficient use of research resources, guide funding decisions and build capacity in EMS research. Other countries have used research agendas to identify barriers and opportunities in EMS research and define national research priorities. The objective of this project is to develop a national EMS research agenda for Canada that will: 1) explore what barriers to EMS research currently exist, 2) identify current strengths and opportunities that may be of benefit to advancing EMS research, 3) make recommendations to overcome barriers and capitalize on opportunities, and 4) identify national EMS research priorities. Paramedics, educators, EMS managers, medical directors, researchers and other key stakeholders from across Canada will be purposefully recruited to participate in this mixed methods study, which consists of three phases: 1) qualitative interviews with a selection of the study participants, who will be asked about their experience and opinions about the four study objectives, 2) a facilitated roundtable discussion, in which all participants will explore and discuss the study objectives, and 3) an online Delphi consensus survey, in which all participants will be asked to score the importance of each topic discovered during the interviews and roundtable as they relate to the study objectives. Results will be analyzed to determine the level of consensus achieved for each topic. A mixed methods approach will be used to address the four study objectives. We anticipate that the keys to success will be: 1) ensuring a representative sample of EMS stakeholders, 2) fostering an open and collaborative roundtable discussion, and 3) adhering to a predefined approach to measure consensus on each topic. Steps have been taken in the methodology to address each of these a priori concerns.


Development and metabolic profiling of a postbiotic complex exhibiting antibacterial activity against skin microorganisms and anti-inflammatory effect on human keratinocytes.
Beyond probiotics, the interest in the application of postbiotics to various fields has been growing. We aimed to develop a novel postbiotic complex (PC) with antibacterial and anti-inflammatory properties. Through antibacterial activity testing against Staphylococcus aureus or Cutibacterium acnes, a PC [a mixture of cell-free supernatants (postbiotics) from probiotic Lactobacillus helveticus (HY7801) and Lactococcus lactis (HY449)] was developed. Anti-inflammatory activity of the PC was investigated using HaCaT keratinocytes treated with S. aureus or C. acnes. PC significantly decreased IL-8 levels and increased hyaluronic acid levels in HaCaT cells cultured with S. aureus or C. acnes. GC-MS based metabolic profiling suggested 2-hydroxyisocaproic acid, hypoxanthine, succinic acid, ornithine, and γ-aminobutyric acid as potential contributing metabolites for the antibacterial and anti-inflammatory effects of PC. The PC developed in this study could be utilized in food, cosmetics, and pharmaceutical products as an alternative or complementary resources of probiotics. The online version contains supplementary material available at 10.1007/s10068-022-01123-x.


Stress Associated with Simulated Transport, Changes Serum Biochemistry, Postmortem Muscle Metabolism, and Meat Quality of Broilers.
Many factors contribute to the stress of transporting broilers from the farm to the processing plant. Using a motion simulation machine, a total of 144 male broilers were employed to determine the effect of motion, vibration, and feed withdrawal during transportation on serum biochemical parameters, postmortem muscle metabolism, and meat quality of broilers. The results indicated that transportation did not affect the activity of lactate dehydrogenase, γ-glutamyl transferase, aspartate aminotransferase, creatine kinase, and glucose in the serum, glutathione peroxidase in the breast and thigh muscle, nitric oxide synthase (NOS) in the breast, and heat stress protein 70 mRNA expression level in the liver (p > 0.05). Serum triiodothyronine, thyroxine, and insulin concentration declined with 2 h transportation (p < 0.05) and recovered with 4 h transportation (p < 0.05). NOS concentration in the thigh increased with 2 h transportation (p < 0.05) and recovered with 4 h transportation (p < 0.05). Two-hour and 4 h transportation increased the activity of superoxide dismutase in both muscles. Malondialdehyde, lactic acid, and drip loss24 h in both thigh and breast muscles increased, and glycogen in both muscles decreased with increasing transportation times (p < 0.05). Two-hour transportation did not influence pH45 min and pH24 h in the breast and thigh muscle, but these indexes decreased with 4 h transportation. This experiment supports and extends previous work that identified transportation as a major risk in relation to bird welfare and meat quality.


Biopsychosocial complexity is correlated with psychiatric comorbidity but not with perceived pain in complex regional pain syndrome type 1 (algodystrophy) of the knee.
The aim of this study was to compare the characteristics of patients suffering from complex regional pain syndrome type 1 ([CRPS], also known as reflex sympathetic dystrophy or algodystrophy) of the knee with those of a matched group of patients experiencing post-traumatic knee pain. The comparisons looked at biopsychosocial complexity (simple versus complex), psychiatric comorbidity and pain intensity. Cross-sectional, single-centre, case-control study using the INTERMED scale, psychiatric diagnostic tools (ICD-10) and visual analogue pain scale. Contingency table and Chi2 tests. One-way analysis of variance for continuous dependent variables. Difference between groups: Tukey's variance test, after the event. For nominal dependent variables, multivariate logistic analysis. Biopsychosocial complexity did not differ between the two groups (p = 0.7). The "complex" patients displayed significantly more psychiatric comorbidity (odds ratio 2.94, 95% confidence interval 1.1-7.8, p < 0.01), independently of whether or not CRPS was present. The pain perceived varied with biopsychosocial complexity only in the control group. The "complex" control patients reported more pain than the "simple" control patients (p < 0.05). The perceived intensity of pain was not different between the "simple" and "complex" patients with CRPS. Biopsychosocial complexity was comparable between the two groups, and was strongly associated with the presence of psychiatric comorbidity. However, unlike with other pain syndromes, with CRPS the intensity of the perceived pain did not vary with biopsychosocial complexity. Early identification of "complex" patients could make it possible to quickly institute targeted management for both groups of patients.


The fungal sexual revolution continues: discovery of sexual development in members of the genus Aspergillus and its consequences.
Asexuality was considered to be a common feature of a large part of fungi, including those of the genus Aspergillus. However, recent advances and the available genomic and genetic engineering technologies allowed to gather more and more indications of a hidden sexuality in fungi previously considered asexual. In parallel, the acquired knowledge of the most suitable conditions for crossings was shown to be crucial to effectively promote sexual reproduction in the laboratory. These discoveries not only have consequences on our knowledge of the biological processes ongoing in nature, questioning if truly asexual fungal species exist, but they also have important implications on other research areas. For instance, the presence of sexuality in certain fungi can have effects on their pathogenicity or on shaping the ecosystem that they normally colonize. For these reasons, further investigations of the sexual potential of Aspergillus species, such as the industrially important A. niger, will be carried on.


Diagnostic performance of mobile cone beam computed tomography versus conventional multi-detector computed tomography in orbital floor fractures: a study on human specimens.
The aim of this study was to evaluate the diagnostic accuracy of mobile cone beam computed tomography (MCBCT) versus multi-detector computed tomography (MDCT) in orbital floor fractures. Twenty-four fresh cadaver heads were used, and one orbital floor was fractured for each head by transconjunctival approach. MDCT and MCBCT were performed on each of the heads. The images obtained were then analysed independently by eight evaluators. The radiological characteristics of the orbital floor fractures were visualized with good interpretation agreement between the two images. The location of the fracture and enophthalmos were identified in a comparable manner with strong agreement (κ=0.93 and κ=0.85, respectively). Measurements of fatty hernias and bone defects showed a strong correlation between the two imaging modalities (Pearson coefficient between 0.64 and 0.71 and between 0.67 and 0.71, respectively). The fracture limits and the presence of bone fragments, an intrasinus fatty hernia, and a fracture of the associated medial orbital wall were visualized in both examinations with good agreement (κ=0.68, κ=0.51, κ=0.57, and κ=0.46, respectively). The soft tissue study showed superiority for MDCT, with a κ<0.0009. MCBCT showed good diagnostic performance in the study of orbital floor fracture characteristics.


Value of intraoperative examination of axillary sentinel nodes in carcinoma of the breast.
The value of frozen sections in the intraoperative examination of sentinel nodes (SN) remains controversial. Accurate frozen sections will spare those patients with node metastasis from a second procedure to complete the axillary dissection. We examined our own experience with intraoperative examination of SN. Between January 1, 2006, and December 31, 2006, we performed 236 sentinel lymph node biopsy procedures that were read as "frozen-section-negative." An additional 47 sentinel lymph node biopsy patients were frozen-section-positive for metastatic disease and underwent immediate completion axillary dissection. At least 1 SN was found in all 283 women (100%). The number of patients with false-negative frozen sections was tallied; patient data were reviewed for a number of variables to see which factors might be associated with a false-negative result. Eleven patients had positive nodes on subsequent examination of the formalin-fixed, hematoxylin and eosin-stained slides; the false-negative rate of intraoperative frozen section was 4.7%. The sensitivity of the negative frozen section was > 95%. The following variables were compared for significance: pathologist, nuclear grade, histologic grade, margins, lymphovascular invasion, tumor type (ductal versus lobular), and estrogen receptor and progesterone receptor values. The only significant variables were lymphovascular invasion (p = 0.019) and presence of in situ ductal carcinoma (p = 0.001). Our data confirm the value of intraoperative examination of SN: > 95% sensitivity. Presence of in situ ductal carcinoma or lymphovascular invasion makes these tumors more likely than others to have micrometastases to SN overlooked.


[A method for the determination of bromide in urine with an ion-sensitive electrode (author's transl)].
A potentiometric method for determining the concentration of bromide in human urine is described. On account of its specificity and precision, this method is especially suited for the determination of slightly elevated bromide concentrations due to occupational exposure to alkyl bromides. The rate of recovery is 102.5 to 112.5%, and the variability coefficients lie between 5.8 and 8.6%. The detection limit is about 0.013 mmol/l. The concentrations of bromide in the urine of a group of normal persons lie between 0.059 and 0.162 mmol/l.


Comparative protein profile of human hepatoma HepG2 cells treated with graphene and single-walled carbon nanotubes: an iTRAQ-coupled 2D LC-MS/MS proteome analysis.
Graphitic nanomaterials are promising candidates for applications in electronics, energy, materials and biomedical areas. Nevertheless, few detailed studies related to the mechanistic understanding of these nanomaterials with the living systems have been performed to date. In the present study, our group applied the iTRAQ-coupled 2D LC-MS/MS approach to analyze the protein profile change of human hepatoma HepG2 cells treated with graphene and single-walled carbon nanotubes (SWCNTs), with the purpose of characterizing the interactions between living system and these nanomaterials at molecular level. Overall 37 differentially expressed proteins involved in metabolic pathway, redox regulation, cytoskeleton formation and cell growth were identified. Based on the protein profile, we found SWCNTs severely interfered the intracellular metabolic routes, protein synthesis and cytoskeletal systems. Moreover, our data suggested that SWCNTs might induce oxidative stress, thereby activating p53-mediated DNA damage checkpoint signals and leading to apoptosis. However, only moderate variation of protein levels for the cells treated with graphene was observed, which indicated graphene was less toxic and might be promising candidate for biomedical applications. We envision that this systematic characterization of cellular response at protein expression level will be of great importance to evaluate biocompatibility of nanomaterials.


A three-dimensional finite element model for biomechanical analysis of the hip.
The objective of this study was to construct a three-dimensional (3D) finite element model of the hip. The images of the hip were obtained from Chinese visible human dataset. The hip model includes acetabular bone, cartilage, labrum, and bone. The cartilage of femoral head was constructed using the AutoCAD and Solidworks software. The hip model was imported into ABAQUS analysis system. The contact surface of the hip joint was meshed. To verify the model, the single leg peak force was loaded, and contact area of the cartilage and labrum of the hip and pressure distribution in these structures were observed. The constructed 3D hip model reflected the real hip anatomy. Further, this model reflected biomechanical behavior similar to previous studies. In conclusion, this 3D finite element hip model avoids the disadvantages of other construction methods, such as imprecision of cartilage construction and the absence of labrum. Further, it provides basic data critical for accurately modeling normal and abnormal loads, and the effects of abnormal loads on the hip.


Determination of melamine in pet food by enzyme immunoassay, high-performance liquid chromatography with diode array detection, and ultra-performance liquid chromatography with tandem mass spectrometry.
Melamine in pet food (fortified or originally contaminated) was determined by enzyme immunoassay (EIA), high-performance liquid chromatography with diode array detection (HPLC-DAD), and ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS). The limits of detection (LOD) for EIA and HPLC-DAD were 0.02 and 0.1 microg/mL, respectively. The linear ranges of the calibration curves for EIA and HPLC-DAD were 0.02-0.5 and 0.1-500 microg/mL, respectively. The coefficient of determinations (r2) of the standard curves for EIA and HPLC were 0.9991 and 0.9999, respectively. Coefficient of variations from both inter- and intra-assay were <9.31%, and recovery range for all concentrations was between 71 and 105%. The r2 values between the EIA and HPLC-DAD methods for melamine analysis of the fortified and originally contaminated samples were 0.9973 and 0.9885. The r2 values for UPLC-MS/MS with HPLC-DAD and with EIA were 0.9566 and 0.9489, respectively.


Distribution of TRPM8-expressing trigeminal nerve fibers in the pons and medulla oblongata of the mouse brain.
Transient receptor potential melastatin 8 (TRPM8), a cold-mediated ion channel, is well known to be expressed in primary sensory neurons; however, limited information is currently available on the distribution of TRPM8-expressing trigeminal nerve fibers in the brainstem. The present study showed the distribution of TRPM8-expressing fibers in the pons and medulla oblongata of the TRPM8 KO mice engineered by knocking in EGFP at the frame of the start codon of TRPM8. In addition, TRPM8-expressing fibers were also observed in the brachium pontis, middle cerebellar peduncle, the sensory root of the trigeminal nerve, and spinal trigeminal tract (sp5). Furthermore, TRPM8-expressing nerve fibers surrounded the somata of HuC/D-positive neurons in the sp5. Moreover, the distribution of TRPM8-expressing fibers from rostral to caudal was visualized in sagittal sections of the mouse brain. The present results also revealed that a high number of TRPM8-expressing fibers colocalized with CTB-labeled fibers in the sp5 following an injection of CTB into the whisker compared to mice's eye and ear. These results show the distribution pathway of TRPM8-expressing fibers in the pons and medulla oblongata and possible involvement in peripheral signaling from the trigeminal nerve.