Gene network coherence based on prior knowledge using direct and indirect relationships.
Gene networks (GNs) have become one of the most important approaches for modeling biological processes. They are very useful to understand the different complex biological processes that may occur in living organisms. Currently, one of the biggest challenge in any study related with GN is to assure the quality of these GNs. In this sense, recent works use artificial data sets or a direct comparison with prior biological knowledge. However, these approaches are not entirely accurate as they only take into account direct gene-gene interactions for validation, leaving aside the weak (indirect) relationships. We propose a new measure, named gene network coherence (GNC), to rate the coherence of an input network according to different biological databases. In this sense, the measure considers not only the direct gene-gene relationships but also the indirect ones to perform a complete and fairer evaluation of the input network. Hence, our approach is able to use the whole information stored in the networks. A GNC JAVA-based implementation is available at: http://fgomezvela.github.io/GNC/. The results achieved in this work show that GNC outperforms the classical approaches for assessing GNs by means of three different experiments using different biological databases and input networks. According to the results, we can conclude that the proposed measure, which considers the inherent information stored in the direct and indirect gene-gene relationships, offers a new robust solution to the problem of GNs biological validation.


Functional characterizations of cocaine- and amphetamine-regulated transcript mRNA expression in rat hypothalamus.
Anatomical relationships of hypothalamic cocaine- and amphetamine-regulated transcript (CART) with other hypothalamic neuropeptides were examined by using in situ hybridization histochemistry and immunohistochemistry. CART mRNA was found in various regions in rat hypothalamus, including the periventricular nucleus, paraventricular nucleus, dorsomedial nucleus, perifornical regions, lateral nucleus, and the arcuate nucleus. In the paraventricular nucleus, CART mRNA is colocalized with vasopressin and corticotropin-releasing factor-containing neurons. Moreover, either fasting or diabetes attenuates CART mRNA expression in the hypothalamus, demonstrating that CART mRNA regulation is related to the fuel availability and peripheral hormonal status. Our findings suggest that the presence of CART mRNA in specific cell groups of the hypothalamus plays a role in hypothalamic regulation of neuroendocrine functions.


A study on serum prolactin levels in schizophrenia: correlation with positive and negative symptoms.
Serum prolactin levels are determined in 116 schizophrenics and 120 control subjects. Values of prolactin levels of the patients are compared with the values of control of the same sex and age group. There is no significant difference between prolactin levels of controls and those with negative or positive symptoms of schizophrenia. Analysis, taking age into account, also does not show any significant difference between patients with positive or negative symptoms and controls. The relationship between nature of symptoms of schizophrenia and serum prolactin levels varies in different studies. The possible reasons for such variations are discussed.


The multiple decrement life table: a unifying framework for cause-of-death analysis in ecology.
The multiple decrement life table is used widely in the human actuarial literature and provides statistical expressions for mortality in three different forms: i) the life table from all causes-of-death combined; ii) the life table disaggregated into selected cause-of-death categories; and iii) the life table with particular causes and combinations of causes eliminated. The purpose of this paper is to introduce the multiple decrement life table to the ecological literature by applying the methods to published death-by-cause information on Rhagoletis pomonella. Interrelations between the current approach and conventional tools used in basic and applied ecology are discussed including the conventional life table, Key Factor Analysis and Abbott's Correction used in toxicological bioassay.


Male breast carcinoma: radiotherapy contributed to favorable local control in two cases and related literature review.
Male breast carcinoma (MBC) is rarely encountered in clinical practice. Due to its paucity, our knowledge of MBC only rely on small or single-institutional studies and sporadic cases. The current guidelines for MBC are extrapolated from its female counterparts Rudlowski (Breast Care (Basel) 3(3):183-189, 2008). Nowadays, MBC is actively studied and viewed as a potentially different entity on the aspects of etiology, biological behavior and prognosis. Thus, special treatment strategy guidelines should be established for MBC. Additionally, advance in the systemic chemotherapy and hormonal therapy also contribute to the local control. The indication of radiotherapy need to be clarified and over-treatment should be avoided. Here we present two cases of MBC in which radiotherapy help to sustain a satisfactory disease free survival. Our cases will provide valuable experience for identifying the role of radiotherapy in MBC.


A comparable, chemical and pharmacological analysis of the traditional Chinese medicinal herbs Oldenlandia diffusa and O. corymbosa and a new valuation of their biological potential.
The herb of Oldenlandia diffusa (Willd.) Roxb. (Family Rubiaceae) is well-known in Chinese folk medicine for the treatment of hepatitis and malignant tumors of the liver, lung and stomach. However, another herb of O. corymbosa (L.) Lam is also used interchangeably in South China for treating the same conditions. To compare the efficacy of the two herbs, the antiproliferative effect of their extracts and the antiangiogenic activity of their main constituents were appraised. The Sulforhodamine B (SRB) assay in human hepatoma HepG2 cells and human colon carcinoma CaCo2 cells and the zebrafish angiogenic model were used for this purpose. The results showed almost no antiproliferative effect of the methanol extracts from O. diffusa and O. corymbosa, while the chloroform extracts exhibited slightly antiproliferative effects. The main components had almost no effect on zebrafish angiogenic vessel formation at the concentrations tested. The results suggest that the mechanism of antitumor activity of O. diffusa may not be attributed to the antiproliferative and antiangiogenic effects.


Description of the female of Simulium (Gomphostilbia) aziruni (Diptera: Simuliidae) and its genetic relationships with members of the Simulium gombakense species-group.
Simulium (Gomphostilbia) aziruni Takaoka, Hashim & Chen was described initially based only on a pupa and a mature larva collected from Peninsular Malaysia. Herein, we describe the morphological characters of the female of S. aziruni for the first time. It resembles those of the other members of the Simulium gombakense species-group by the genital fork with a distinct projection directed medioposteriorly from each arm and claw with a large basal tooth. Cytochrome c oxidase I (COI) barcoding analysis indicates that S. aziruni is the sister species of S. maleewongae, but both are distantly separated by a genetic distance of 4.9%.


Preoperative hearing predicts postoperative hearing.
Optimal hearing is one goal of otologic surgery. It is generally presumed that hearing thresholds after tympanoplasty-mastoidectomy surgery are determined by remaining anatomy. We assessed the effect of the disease process on hearing after surgery, and our data do not support this presumption. We studied the relationship between preoperative and postoperative hearing across tympanoplasties with differing anatomies in 124 patients without ossicular reconstruction with prostheses or bone. Our results indicate that poor hearing before surgery is associated with poor hearing after surgery, regardless of anatomy (type of tympanoplasty). This relationship holds for both the airbone gap and the speech-reception threshold. When considering ossicular reconstruction, the surgeon should remember that the disease process itself affects hearing in addition to the physical attributes of the ear. These results should be considered in preoperative counseling, as well as in the interpretation of the otologic literature.


Strong Ligand Stabilization Based on π-Extension in a Series of Ruthenium Terpyridine Water Oxidation Catalysts.
The substitution behavior of the monodentate Cl ligand of a series of ruthenium(II) terpyridine complexes (terpyridine (tpy)=2,2':6',2''-terpyridine) has been investigated. 1 H NMR kinetic experiments of the dissociation of the chloro ligand in D2 O for the complexes [Ru(tpy)(bpy)Cl]Cl (1, bpy=2,2'-bipyridine) and [Ru(tpy)(dppz)Cl]Cl (2, dppz=dipyrido[3,2-a:2',3'-c]phenazine) as well as the binuclear complex [Ru(bpy)2 (tpphz)Ru(tpy)Cl]Cl3 (3 b, tpphz=tetrapyrido[3,2-a:2',3'-c:3'',2''-h:2''',3'''-j]phenazine) were conducted, showing increased stability of the chloride ligand for compounds 2 and 3 due to the extended π-system. Compounds 1-5 (4=[Ru(tbbpy)2 (tpphz)Ru(tpy)Cl](PF6 )3 , 5=[Ru(bpy)2 (tpphz)Ru(tpy)(C3 H8 OS)/(H2 O)](PF6 )3 , tbbpy=4,4'-di-tert-butyl-2,2'-bipyridine) are tested for their ability to run water oxidation catalysis (WOC) using cerium(IV) as sacrificial oxidant. The WOC experiments suggest that the stability of monodentate (chloride) ligand strongly correlates to catalytic performance, which follows the trend 1>2>5≥3>4. This is also substantiated by quantum chemical calculations, which indicate a stronger binding for the chloride ligand based on the extended π-systems in compounds 2 and 3. Additionally, a theoretical model of the mechanism of the oxygen evolution of compounds 1 and 2 is presented; this suggests no differences in the elementary steps of the catalytic cycle within the bpy to the dppz complex, thus suggesting that differences in the catalytic performance are indeed based on ligand stability. Due to the presence of a photosensitizer and a catalytic unit, binuclear complexes 3 and 4 were tested for photocatalytic water oxidation. The bridging ligand architecture, however, inhibits the effective electron-transfer cascade that would allow photocatalysis to run efficiently. The findings of this study can elucidate critical factors in catalyst design.


Methods to assess tissue permeability.
An essential requirement for adequate organ performance is the formation of permeability barriers that separate and maintain compartments of distinctive structure and function. The endothelial cell lining of the vasculature defines a semipermeable barrier between the blood and interstitial spaces of all organs. Disruption of the endothelial cell barrier can result in increased permeability and vascular leak. These effects are associated with multiple systemic disease processes and can accompany acute tissue responses to injury. The mechanisms that control barrier function are complex and their full understanding requires a multidisciplinary approach. The use of in vivo permeability data often complements molecular findings and adds power to the studies. The interaction of multiple cell types and tissues present only in mammalian models allows for testing of hypothesis and establishing the physiological significance of the results. In this chapter we describe simple methods that can be used systematically to measure the permeability profile of several organs.


A new intensive care worksheet.
This article presents a new manual daily worksheet for recording data on a patient's status in an Intensive Care Unit. It permits a rapid view of the whole picture of the patient's condition at a certain hour since the system of recording is based on the time an event happened. Only one single page is used for each day. Space is provided for essential data, ventilatory parameters, laboratory results, fluid balance, drug therapy and special treatments. Attended staff, invited consultants as well as nurses add written notes which complete the picture provided by numbers. It does not replace the computerized interpretation, statistical analysis or storage of data, but it comes as an easy-to-use daily tool at the bedside.


Can dynamic neutron scattering help to understand a thermodynamic variant of an internal quantum-mechanical experiment in the angstrom range?
A chain of ideas is described connecting the theory of quantum-mechanical experiments with practical research in the relaxation of liquids, biological materials, and materials science. The chain culminates at the proposal of an experimentum crucis comparing dynamic neutron scattering, dynamic calorimetry, and computer simulation of the same substances at the crossover region of the dynamic glass transition. The conclusiveness of the experimentum crucis backwards the chain is discussed. The role of relaxation of liquids in confining geometries is also discussed, especially with respect to the confirmation of the von Laue variant for the characteristic length of glass transition as alternative to their Gibbs treatment that results in too large lengths.


Avian malaria in captive psittacine birds: detection by microscopy and 18S rRNA gene amplification.
A cross-sectional survey was conducted to estimate the occurrence of malaria infection among captive psittacine birds (n=127) from three zoological gardens in Brazil. Malaria infection was evaluated by the association of direct examination of blood smears with amplification of the 18SSU rRNA gene of the Plasmodium genus, demonstrating an overall occurrence of 36%. Most infected bird species were Amazona aestiva (28/73), Ara ararauna (6/10), and Amazona amazonica (3/10). The low parasitemias observed among the infected birds suggest a chronic infection. The sequence analyses of 10 isolates indicate a potential occurrence of four distinct Plasmodium lineages. These findings provide new data on malarial infection in captive psittacine birds, and emphasize the need for better control of importation and exportation of these birds.


Looking for Drugs in All the Wrong Places: Use of GCPII Inhibitors Outside the Brain.
In tribute to our friend and colleague Michael Robinson, we review his involvement in the identification, characterization and localization of the metallopeptidase glutamate carboxypeptidase II (GCPII), originally called NAALADase. While Mike was characterizing NAALADase in the brain, the protein was independently identified by other laboratories in human prostate where it was termed prostate specific membrane antigen (PSMA) and in the intestines where it was named Folate Hydrolase 1 (FOLH1). It was almost a decade to establish that NAALADase, PSMA, and FOLH1 are encoded by the same gene. The enzyme has emerged as a therapeutic target outside of the brain, with the most notable progress made in the treatment of prostate cancer and inflammatory bowel disease (IBD). PSMA-PET imaging with high affinity ligands is proving useful for the clinical diagnosis and staging of prostate cancer. A molecular radiotherapy based on similar ligands is in trials for metastatic castration-resistant prostate cancer. New PSMA inhibitor prodrugs that preferentially block kidney and salivary gland versus prostate tumor enzyme may improve the clinical safety of this radiotherapy. The wide clinical use of PSMA-PET imaging in prostate cancer has coincidentally led to clinical documentation of GCPII upregulation in a wide variety of tumors and inflammatory diseases, likely associated with angiogenesis. In IBD, expression of the FOLH1 gene that codes for GCPII is strongly upregulated, as is the enzymatic activity in diseased patient biopsies. In animal models of IBD, GCPII inhibitors show substantial efficacy, suggesting potential theranostic use of GCPII ligands for IBD.


Identification of inferior pancreaticoduodenal artery during pancreaticoduodenectomy using augmented reality-based navigation system.
In pancreaticoduodenectomy (PD), early ligation of the inferior pancreaticoduodenal artery (IPDA) before efferent veins has been advocated to decrease blood loss by congestion of the pancreatic head to be resected. In this study, we herein report the utility of early identification of the IPDA using an augmented reality (AR)-based navigation system (NS). Seven nonconsecutive patients underwent PD using AR-based NS. After paired-point matching registration, the reconstructed image obtained by preoperative computed tomography (CT) was fused with a real-time operative field image and displayed on 3D monitors. The vascular reconstructed images, including the superior mesenteric artery, jejunal artery, and IPDA were visualized to facilitate image-guided surgical procedures. We compared operating time and intraoperative blood loss of six patients who successfully underwent identification of IPDA using AR-based NS (group A) with nine patients who underwent early ligation of IPDA without using AR (group B) and 18 patients who underwent a conventional PD (group C). The IPDA or the jejunal artery was rapidly identified and ligated in six patients. The mean operating time and intraoperative blood loss in group A was 415 min and 901 ml, respectively. There was no significant difference in operating time and intraoperative blood loss among the groups. The AR-based NS provided precise anatomical information, which allowed the surgeons to rapidly identify and perform early ligation of IPDA in PD.


Automated spike detection: Which software package?
We assessed three commercial automated spike detection software packages (Persyst, Encevis and BESA) to see which had the best performance. Thirty prolonged EEG records from people aged at least 16 years were collected and 30-minute representative epochs were selected. Interictal epileptiform discharges (IEDs) were marked by three human experts and by all three software packages. For each 30-minutes selection and for each 10-second epoch we measured whether or not IEDs had occurred. We defined the gold standard as the combined detections of the experts. Kappa scores, sensitivity and specificity were estimated for each software package. Sensitivity for Persyst in the default setting was 95% for 30-minute selections and 82% for 10-second epochs. Sensitivity for Encevis was 86% (30-minute selections) and 61% (10-second epochs). The specificity for both packages was 88% for 30-minute selections and 96%-99% for the 10-second epochs. Interrater agreement between Persyst and Encevis and the experts was similar than between experts (0.67-0.83 versus 0.63-0.67). Sensitivity for BESA was 40% and specificity 100%. Interrater agreement (0.25) was low. IED detection by the Persyst automated software is better than the Encevis and BESA packages, and similar to human review, when reviewing 30-minute selections and 10-second epochs. This findings may help prospective users choose a software package.


Screening for asymptomatic deep vein thrombosis in COVID-19 patients admitted to the medical ward: a cross-sectional study.
Patients with COVID-19 have an increased risk for venous thrombo-embolism (VTE), especially pulmonary embolism. The exact prevalence of asymptomatic DVT is not known, as is the usefulness of screening for DVT in patients admitted to ward with COVID-19. We have studied the prevalence of asymptomatic DVT. We performed a cross-sectional observational multi-center study at four university medical centers in The Netherlands. All adult patients admitted with COVID-19 to a medical ward were eligible for inclusion, including patients who were transferred back from the ICU to the ward. The study protocol consisted of weekly cross-sectional rounds of compression ultrasound. In total, 125 patients were included in the study. A significant proportion of patients (N = 34 (27%)) had developed a VTE during their admission for COVID-19 before the study ultrasound was performed. In most VTE cases (N = 27 (79%)) this concerned pulmonary embolism. A new asymptomatic DVT was found in 5 of 125 patients (4.0%; 95% CI 1.3-9.1%) (Table 2). Nine patients (7.2%; 95% CI 3.3-13.2%) developed a VTE (all PE) diagnosed within 28 days after the screening US was performed. We have shown a low prevalence (4%) of newly discovered asymptomatic DVT outside the ICU-setting in COVID-19 patients. Despite this low prevalence, nine patients developed PE (7%) within 28 days after ultrasound. This favors the hypothesis of local thrombus formation in the lungs. Based on our findings and literature, we do not recommend US-screening of asymptomatic patients with COVID-19 admitted to the ward.


Immunosuppressive glycoproteins associate with breast tumor fibrosis and aggression.
Tumors feature elevated sialoglycoprotein content. Sialoglycoproteins promote tumor progression and are linked to immune suppression via the sialic acid-Siglec axis. Understanding factors that increase sialoglycoprotein biosynthesis in tumors could identify approaches to improve patient response to immunotherapy. We quantified higher levels of sialoglycoproteins in the fibrotic regions within human breast tumor tissues. Human breast tumor subtypes, which are more fibrotic, similarly featured increased sialoglycoprotein content. Further analysis revealed the breast cancer cells as the primary cell type synthesizing and secreting the tumor tissue sialoglycoproteins and confirmed that the more aggressive, fibrotic breast cancer subtypes expressed the highest levels of sialoglycoprotein biosynthetic genes. The more aggressive breast cancer subtypes also featured greater infiltration of immunosuppressive SIGLEC7, SIGLEC9, and SIGLEC10-pos myeloid cells, indicating that triple-negative breast tumors had higher expression of both immunosuppressive Siglec receptors and their cognate ligands. The findings link sialoglycoprotein biosynthesis and secretion to tumor fibrosis and aggression in human breast tumors. The data suggest targeting of the sialic acid-Siglec axis may comprise an attractive therapeutic target particularly for the more aggressive HER2+ and triple-negative breast cancer subtypes.


The influence of lung density corrections on treatment planning for primary breast cancer.
Primary breast cancer is generally treated with opposed radiation beams oriented tangentially with respect to the breast. This technique attempts to minimize the dose to the lung and other normal tissues, while at the same time producing a uniform dose distribution throughout the irradiated breast. Although a part of the lung is always included in the tangential breast fields, the effect of this low density tissue on the dose distribution is rarely taken into account. In the present work, the effect of lung density correction on the dose distribution resulting from tangential breast fields is analyzed. Treatment plans for a series of 34 patients treated for breast cancer have been performed using CT data. To study the effect of density corrections on the tangential field treatment plans for these patients, eight separate treatment plans for each patient have been optimized. For each of four photon energies (60Co, and 4, 6, and 10 MV X rays), treatment plans have been optimized for each patient when density correction is employed, and when unit density is assumed. Four additional dose calculations have been obtained for each patient corresponding to use of the unit density plan, but with density corrections employed in the calculation. The effects that density correction has on the wedge angles used, on the maximum dose ("hot spot") for each of several cross-sectional cuts, on the prescription isodose level which is chosen for each plan, and on homogeneity of the dose distribution over the target volume are all analyzed for the above described plans.


Integrating health-related data from various sources: combining surveys, records and routine data.
The paper discusses the necessity of combining data from various sources in order to enhance their usefulness for a variety of applications. As future data use can hardly be forseen in advance, major data sets in health services should fulfill several formal requirements in order to make them suitable for future linkage. These formal requirements are that there be references to defined populations, to specific persons, to defined time periods, to specific places or regions. It would be necessary for terms, definition and classification schemes to agree between data sets which are to be linked and be in wide use. Three facets of data linkage are discussed specifically namely linking data at one level of aggregation, linking different data components, and combining data sets from different sources at several levels of aggregation. Three examples are provided, describing linkages of data from various sources for epidemiological studies and a study in health services research. They show that at this point in descriptive epidemiological studies linkage on the basis of regions is of great importance. This implies that it would be desirable for large scale data collection activities in health services to provide for a uniform representation of the geographic areas. Such uniformity would greatly enhance the linkage potential of data sets and thus their usefulness for small area and regional analyses.


Theoretical and Spectroscopic Characterization of API-Related Azoles in Solution and in Solid State.
Azoles are a family of five-membered azacyclic compounds with relevant biological and pharmacological activity. Different subclasses of azoles are defined depending on the atomic arrangement and the number of nitrogen atoms present in the ring: pyrazoles, indazoles, imidazoles, benzimidazoles, triazoles, benzotriazoles, tetrazoles and pentazoles. The complete characterization of their structure and the knowledge about their crystal packing and physical and chemical properties are of vital importance for the advancement in the design of new azole-containing drugs. In this review, we report the latest recent contributions to azole chemistry, in particular, those in which theoretical studies have been performed.


Population genetic attributes of common leopard (Panthera pardus fusca) from Uttarkashi, Western Himalayas.
The common leopard (Panthera pardus fusca), which persists in most of its historic range, is experiencing steady population decline due to habitat loss, anthrophonic disturbances, illegal poaching for their body parts, and retaliatory killings in response to the leopard-human conflicts. We analysed 143 scats samples and identified 32 unique leopards following a selected panel of seven loci with cumulative PID sibs 5.30E-04. We observed moderate genetic diversity at nuclear (Ho = 0.600 ± 0.06) and mitochondrial markers (Hd = 0.569 ± 0.009; π = 0.001 ± 0.0002) and found sub-structuring in the leopard population at Uttarkashi, Western Himalayas. The present study exhibits the utility of non-invasive genetics in monitoring the leopard population and paves the path to investigate population genetic parameters in further studies.


Pharmacokinetics and physiologic effects of intramuscularly administered xylazine hydrochloride-ketamine hydrochloride-butorphanol tartrate alone or in combination with orally administered sodium salicylate on biomarkers of pain in Holstein calves following castration and dehorning.
To determine the pharmacokinetic parameters of xylazine, ketamine, and butorphanol (XKB) administered IM and sodium salicylate (SAL) administered PO to calves and to compare drug effects on biomarkers of pain and distress following sham and actual castration and dehorning. 40 Holstein bull calves from 3 farms. Calves weighing 108 to 235 kg (n = 10 calves/group) received one of the following treatments prior to sham (period 1) and actual (period 2) castration and dehorning: saline (0.9% NaCl) solution IM (placebo); SAL administered PO through drinking water at concentrations from 2.5 to 5 mg/mL from 24 hours prior to period 1 to 48 hours after period 2; butorphanol (0.025 mg/kg), xylazine (0.05 mg/kg), and ketamine (0.1 mg/kg) coadministered IM immediately prior to both periods; and a combination of SAL and XKB (SAL+XKB). Plasma drug concentrations, average daily gain (ADG), chute exit velocity, serum cortisol concentrations, and electrodermal activity were evaluated. ADG (days 0 to 13) was significantly greater in the SAL and SAL+XKB groups than in the other 2 groups. Calves receiving XKB had reduced chute exit velocity in both periods. Serum cortisol concentrations increased in all groups from period 1 to period 2. However, XKB attenuated the cortisol response for the first hour after castration and dehorning and oral SAL administration reduced the response from 1 to 6 hours. Administration of XKB decreased electrodermal activity scores in both periods. SAL administered PO through drinking water decreased cortisol concentrations and reduced the decrease in ADG associated with castration and dehorning in calves.


Deformability of passive and activated neutrophils in children with Gram-negative septicemia.
Animal experiments suggest that obstruction of small vessels by polymorphonuclear neutrophils (PMNs) may contribute to the disturbed microcirculation in septic shock. The purpose of this investigation was to study deformability and volume of passive and activated PMNs and immature neutrophils in 15 children with Gram-negative septicemia and in 20 healthy children. Membrane cytoplasm tongues of neutrophils were aspirated by means of a micropipette system into 2.5-microm (diameter) pipettes for 60 s. Tongue growth was used as an indicator of deformability and the cell volume was calculated from the cell circumference before aspiration. Septicemic children showed higher percentages of immature neutrophils (38+/-13%) and activated PMN (12+/-5%) than healthy children (3+/-2% and 3+/-2%). In septicemic children, cellular volume of passive neutrophils decreased progressively with increasing maturity from myeloblasts (493+/-105 fL) to mature PMNs (346+/-29 fL) and the final tongue length in the micropipette increased from 2.7+/-1.1 to 8.5+/-1.8 microm during maturation. The final tongue length of activated PMNs was decreased by 60% compared with that of passive PMNs. The increased number of rigid activated and immature neutrophils may contribute to impaired microcirculation in septicemic patients.


Data infrastructures for AI in medical imaging: a report on the experiences of five EU projects.
Artificial intelligence (AI) is transforming the field of medical imaging and has the potential to bring medicine from the era of 'sick-care' to the era of healthcare and prevention. The development of AI requires access to large, complete, and harmonized real-world datasets, representative of the population, and disease diversity. However, to date, efforts are fragmented, based on single-institution, size-limited, and annotation-limited datasets. Available public datasets (e.g., The Cancer Imaging Archive, TCIA, USA) are limited in scope, making model generalizability really difficult. In this direction, five European Union projects are currently working on the development of big data infrastructures that will enable European, ethically and General Data Protection Regulation-compliant, quality-controlled, cancer-related, medical imaging platforms, in which both large-scale data and AI algorithms will coexist. The vision is to create sustainable AI cloud-based platforms for the development, implementation, verification, and validation of trustable, usable, and reliable AI models for addressing specific unmet needs regarding cancer care provision. In this paper, we present an overview of the development efforts highlighting challenges and approaches selected providing valuable feedback to future attempts in the area.Key points• Artificial intelligence models for health imaging require access to large amounts of harmonized imaging data and metadata.• Main infrastructures adopted either collect centrally anonymized data or enable access to pseudonymized distributed data.• Developing a common data model for storing all relevant information is a challenge.• Trust of data providers in data sharing initiatives is essential.• An online European Union meta-tool-repository is a necessity minimizing effort duplication for the various projects in the area.


Immunocytochemical distribution of [Met]enkephalin-Arg-Gly-Leu immunoreactivity in the rat diencephalon.
Recently, [Met]Enkephalin-Arg-Gly-Leu (MEAGL) was isolated from bovine adrenal glands, and it was found to be derived exclusively from proenkephalin. Therefore, we investigated the distribution of MEAGL-like immunoreactive neuronal perikarya and fibers in the rat diencephalon pretreated with colchicine by PAP immunocytochemistry. In the thalamus MEAGL immunoreactive neuronal perikarya were distributed in the paraventricular nucleus and the ventral part of the lateral geniculate nucleus. Immunoreactive fibers were found in the paraventricular, paracentral, anteroventral, reuniens and rhomboid nuclei. In addition, immunoreactive fibers were also noted in the anterior pretectal nucleus. In the hypothalamus, immunoreactive neuronal perikarya were observed in the medial preoptic area, anterior and lateral hypothalamic nuclei, perifornical region, parvocellular and postero-magnocellular regions of paraventricular nucleus, ventromedial nucleus, dorsomedial nucleus, arcuate nucleus, premammillary, medial mammillary and lateral mammillary nuclei. The distribution of immunoreactive fibers was similar to that of neuronal perikarya. However, immunoreactive fibers were also observed in the supraoptic and suprachiasmatic nuclei where no immunoreactive neuronal perikarya were detected. Numerous immunoreactive fibers were detected in the external layer of the median eminence, but there were few in the internal layer. The similarity and difference in the distribution between MEAGL and other proenkephalin peptides such as [Met]enkephalin were also discussed.


Contraceptive vaginal ring use for women has less adverse metabolic effects than an oral contraceptive.
This study compared metabolic, hormonal and lipid profiles before and during use of a contraceptive vaginal ring (RING) releasing 15 mcg ethinyl estradiol (EE) and 120 mcg etonogestrel per day NuvaRing, Organon USA Inc., Roseland, NJ versus a low-dose oral contraceptive (PILL) containing 20 mcg EE and 100 mcg levonorgestrel daily (Aviane, Barr Pharmaceuticals Inc., Pomona, NY). Sixty-five women were randomized to either the RING or PILL treatment for five cycles. In the pretreatment cycle (Cycle Days 2-5) and during Weeks 2 and 3 of the fifth treatment cycle, a 75-g oral glucose tolerance test (OGTT) was performed. Baseline samples were used to evaluate basal hormonal, metabolic and lipid levels. Forty-two women completed the study. Basal insulin resistance (HOMA-IR) was slightly decreased, whereas a significant reduction in the insulin sensitivity index (IS(OGTT)) was found in women on PILL therapy compared to those in the RING group (p<.035). Pancreatic beta-cell function was not significantly altered with either treatment. The lower-dose, nonoral hormonal RING had a lesser impact on carbohydrate metabolism and greater reduction of free androgen and dehydroepiandrosterone sulfate levels than PILL treatment.


Retrograde percutaneous coronary intervention of chronic total occlusion via discontinuous septal channels.
The study aims to investigate the safety and feasibility of retrograde CTO intervention via collateral connection grade 0 (CC-0) septal channel and to identify predictors of collateral tracking failure. Guidewire crossing a collateral channel is a critical step for successful retrograde percutaneous coronary intervention (PCI) of chronic total occlusion (CTO). Retrograde PCI was attempted in 122 cases of CTO with CC-0 septal collaterals from December 2018 to May 2021. A hydrophilic polymer coating guidewire was used for crossing all intended CC-0 collaterals. A multivariable logistic regression analysis was performed to identify the predictors of guidewire tracking failure via the CC-0 collaterals. Successful guidewire tracking via CC-0 septal channel was achieved in 98 (80.3%) of 122 cases. The independent predictors of CC-0 septal channel guidewire tracking failure included well-developed non-septal collateral (OR: 5.297, 95% CI: 1.107-25.353, p = 0.037) and the ratio length of posterior descending artery (PDA) versus the distance of PDA ostium to cardiac apex ≤2/3 (OR: 3.970, 95% CI: 1.454-10.835, p = 0.007). Collateral perforation, target vessel perforation, and cardiac tamponade occurred in 5 (4.1%), 3 (2.5%), and 6 (4.9%) cases, respectively. There were no complications requiring emergency cardiac surgery or revascularization of nontarget vessel. Retrograde PCI via CC-0 septal channels with a hydrophilic polymer-coated guidewire is feasible and safe in patients with CTO. Well-developed nonseptal collaterals and short PDA length influence the procedure success and the risk of guidewire tracking failure via CC-0 septal channels.


Correlations between kynurenines in plasma and CSF, and their relation to markers of Alzheimer's disease pathology.
Altered levels of kynurenines in blood and cerebrospinal fluid (CSF) have been reported in Alzheimer's disease (AD). However, it is still largely unknown whether peripheral kynurenine concentrations resemble those found in CSF and how they relate to AD pathology. We therefore studied correlations between kynurenines in plasma and CSF and their associations with CSF amyloid-beta (Aβ1-42) and tau levels in patients from the memory clinic spanning the whole cognitive spectrum. The Biobank Alzheimer Center Limburg study is a prospective cohort study of consecutive patients referred to the memory clinic of the Alzheimer Center Limburg. Plasma and CSF concentrations of tryptophan (TRP), eight kynurenines and neopterin from 138 patients were determined by means of LC-MS/MS. Additionally, CSF Aβ1-42, total-tau (t-tau) and phosphorylated tau (p-tau) concentrations were determined using commercially available single-parameter ELISA methods. Partial correlations were used to analyze cross-sectional associations between kynurenines in plasma and CSF and their relation to AD related CSF-biomarkers adjusted for age, sex, educational level, and kidney function. Moderate to strong correlations were observed between plasma and CSF levels for quinolinic acid (QA; r = 0.63), TRP (r = 0.47), anthranilic acid (r = 0.59), picolinic acid (r = 0.55), and the kynurenine (KYN)/TRP ratio (KTR; r = 0.55; all p < 0.0001), while other kynurenines correlated only weakly with their corresponding CSF values. No correlations were found between plasma and CSF levels of KA/QA. Several kynurenines were also weakly correlated with Aβ1-42, t-tau or p-tau. Plasma levels of KA/QA were negatively correlated with Aβ1-42 (r = -0.21, p < 0.05). Plasma levels of TRP were negatively correlated with t-tau (r = -0.19) and levels of KYN with p-tau (r = -0.18; both p < 0.05). CSF levels of KYN (r = 0.20, p < 0.05), KA (r = 0.23, p < 0.01), and KTR (r = 0.18, p < 0.05) were positively correlated with Aβ1-42. Finally, TRP and KYN were negatively (r = -0.22 and r = -0.18, respectively), and neopterin positively (r = 0.19) correlated with p-tau (all p < 0.05). Plasma concentrations of TRP, KP metabolites, KTR, and neopterin all significantly correlated positively with their corresponding CSF concentrations, but many correlations were weak. Additionally, our results suggest a relation between higher kynurenine levels and lower AD pathology load. These results need verification in future studies and require more research into (shared) underlying mechanisms.


Lack of an effect of oral iron administration on mycophenolic acid pharmacokinetics in stable renal transplant recipients.
To determine if coadministration of polysaccharide iron complex and slow-release ferrous sulfate alter the absorption of mycophenolic acid (MPA), and to examine the potential influence of dosing relative to mycophenolate mofetil (MMF) administration and the effect of immediate- versus sustained-release iron products on the steady-state pharmacokinetics of MPA. Prospective, open-label, three-phase, crossover, steady-state pharmacokinetic study. National Institutes of Health-sponsored General Clinical Research Center at a university medical center. Twelve adult (mean age 50 yrs) renal transplant recipients who were receiving concomitant iron and MMF maintenance therapy. Oral iron therapy was coadministered with MMF on days -6-0, MMF was administered alone on days 1-8 (control phase), then oral iron therapy was administered 2 hours after MMF administration on days 9-16. Baseline demographics, concurrent drug regimens, and clinical laboratory values were assessed. Blood samples were obtained at baseline and at 1, 2, 3, 4, 6, 8, and 12 hours after MMF administration on days 0, 8, and 16. The MPA levels were measured by high-performance liquid chromatography. We found no significant differences in the dose-standardized area under the concentration-time curve from 0-12 hours (AUC(0-12)) for MPA between the control phase (39.66 +/- 8.70 mg mg x hr/L) and the concomitant ferrous sulfate or dose-separated ferrous sulfate (37.56 +/- 9.95 or 32.84 +/- 8.43 mg x hr/L, respectively, p>0.05) phases. Dose-standardized AUC(0-12) values for MPA did not significantly differ after the concomitant administration of polysaccharide iron complex from that of the control phase (48.46 +/- 9.68 and 43.80 +/- 9.46 mg x hr/L, respectively, p=0.065). However, the AUC(0-12) for MPA significantly increased when polysaccharide iron complex was administered 2 hours after MMF (53.41 +/- 11.75 mg x hr/L, p=0.012). Maximum concentrations and times to reach maximum concentrations remained consistent across all study phases in each arm of the trial (p>0.05). Multiple doses of iron therapy-slow-release ferrous sulfate, or polysaccharide iron complex-did not significantly reduce systemic exposure to MMF, as measured by using AUC(0-12) values.


Ameliorating effect of FK614, a novel nonthiazolidinedione peroxisome proliferator-activated receptor gamma agonist, on insulin resistance in Zucker fatty rat.
Effect of 3-(2,4-dichlorobenzyl)-2-methyl-N-(pentylsulfonyl)-3H-benzimidazole-5-carboxamide (FK614), a novel nonthiazolidinedione peroxisome proliferator-activated receptor (PPAR) gamma agonist, on glucose tolerance and insulin resistance in peripheral tissues and in liver using Zucker fatty rats (genetically obese and insulin-resistant) was evaluated and compared to other insulin sensitizers. FK614 (0.32, 1 and 3.2 mg/kg), two thiazolidinedione PPAR gamma agonists, rosiglitazone (0.1, 0.32, 1 and 3.2 mg/kg) and pioglitazone (1, 3.2 and 10 mg/kg), and a biguanide, metformin (320 and 1000 mg/kg), were orally administered to Zucker fatty rats once a day for 14 days. Zucker fatty rats treated with FK614 and rosiglitazone were subjected to evaluation by oral glucose tolerance test. Ameliorating effect of each compound on peripheral and hepatic insulin resistance was evaluated using a euglycemic-hyperinsulineamic clamp procedure. FK614 and rosiglitazone dose-dependently improved impaired glucose tolerance in Zucker fatty rats. In addition, FK614 dose-dependently ameliorated peripheral and hepatic insulin resistance in Zucker fatty rats, with the degree of its effect in peripheral tissues almost equivalent to that in liver when compared at each dose tested. Similar data indicating ameliorating effects on insulin resistance was obtained for rosiglitazone and pioglitazone. Metformin showed less potent effects than other insulin sensitizers and its effect in liver tended to be greater than that in peripheral tissues. These findings suggest clinical potential for FK614 as a treatment of type 2 diabetes, acting by ameliorating insulin resistance both in peripheral tissues and liver.


Inequity between male and female coverage in state infertility laws.
To analyze state insurance laws mandating coverage for male factor infertility and identify possible inequities between male and female coverage in state insurance laws. We identified states with laws or codes related to infertility insurance coverage using the National Conference of States Legislatures' and the National Infertility Association's websites. We performed a primary, systematic analysis of the laws or codes to specifically identify coverage for male factor infertility services. Not applicable. Not applicable. Not applicable. The presence or absence of language in state insurance laws mandating coverage for male factor infertility care. There are 15 states with laws mandating insurance coverage for female factor infertility. Only eight of those states (California, Connecticut, Massachusetts, Montana, New Jersey, New York, Ohio, and West Virginia) have mandates for male factor infertility evaluation or treatment. Insurance coverage for male factor infertility is most specific in Massachusetts, New Jersey, and New York, yet significant differences exist in the male factor policies in all eight states. Three states (Massachusetts, New Jersey, and New York) exempt coverage for vasectomy reversal. Despite national recommendations that male and female partners begin infertility evaluations together, only 8 of 15 states with laws mandating infertility coverage include coverage for the male partner. Excluding men from infertility coverage places an undue burden on female partners and risks missing opportunities to diagnose serious male health conditions, correct reversible causes of infertility, and provide cost-effective treatments that can downgrade the intensity of intervention required to achieve a pregnancy.


Identification of markers for predicting prognosis and endocrine metabolism in nasopharyngeal carcinoma by miRNA-mRNA network mining and machine learning.
Nasopharyngeal cancer (NPC) has a high incidence in Southern China and Asia, and its survival is extremely poor in advanced patients. MiRNAs play critical roles in regulating gene expression and serve as therapeutic targets in cancer. This study sought to disclose key miRNAs and target genes responsible for NPC prognosis and endocrine metabolism. Three datasets (GSE32960, GSE70970, and GSE102349) of NPC samples came from Gene Expression Omnibus (GEO). Limma and WGCNA were applied to identify key prognostic miRNAs. There were 12 types of miRNA tools implemented to study potential target genes (mRNAs) of miRNAs. Univariate Cox regression and stepAIC were introduced to construct risk models. Pearson analysis was conducted to analyze the correlation between endocrine metabolism and RiskScore. Single-sample gene set enrichment analysis (ssGSEA), MCP-counter, and ESTIMATE were performed for immune analysis. The response to immunotherapy was predicted by TIDE and SubMap analyses. Two key miRNAs (miR-142-3p and miR-93) were closely involved in NPC prognosis. The expression of the two miRNAs was dysregulated in NPC cell lines. A total of 125 potential target genes of the key miRNAs were screened, and they were enriched in autophagy and mitophagy pathways. Five target genes (E2F1, KCNJ8, SUCO, HECTD1, and KIF23) were identified to construct a prognostic model, which was used to divide patients into high group and low group. RiskScore was negatively correlated with most endocrine-related genes and pathways. The low-risk group manifested higher immune infiltration, anticancer response, more activated immune-related pathways, and higher response to immunotherapy than the high-risk group. This study revealed two key miRNAs that were highly contributable to NPC prognosis. We delineated the specific links between key miRNAs and prognostic mRNAs with miRNA-mRNA networks. The effectiveness of the five-gene model in predicting NPC prognosis as well as endocrine metabolism provided a guidance for personalized immunotherapy in NPC patients.


Egg-laying substrate selection for optimal camouflage by quail.
Camouflage is conferred by background matching and disruption, which are both affected by microhabitat. However, microhabitat selection that enhances camouflage has only been demonstrated in species with discrete phenotypic morphs. For most animals, phenotypic variation is continuous; here we explore whether such individuals can select microhabitats to best exploit camouflage. We use substrate selection in a ground-nesting bird (Japanese quail, Coturnix japonica). For such species, threat from visual predators is high and egg appearance shows strong between-female variation. In quail, variation in appearance is particularly obvious in the amount of dark maculation on the light-colored shell. When given a choice, birds consistently selected laying substrates that made visual detection of their egg outline most challenging. However, the strategy for maximizing camouflage varied with the degree of egg maculation. Females laying heavily maculated eggs selected the substrate that more closely matched egg maculation color properties, leading to camouflage through disruptive coloration. For lightly maculated eggs, females chose a substrate that best matched their egg background coloration, suggesting background matching. Our results show that quail "know" their individual egg patterning and seek out a nest position that provides most effective camouflage for their individual phenotype.


A new methodology to determine the effect of the adsorbate-adsorbent interactions on the analgesic adsorption onto activated carbon using kinetic and calorimetry data.
This work proposes a new methodology to determine the adsorption mechanism for salicylic acid and paracetamol on activated carbon based on the physicochemical characteristics of adsorbent and adsorbates. The methodology is divided into two parts: the determination of adsorption kinetics (order and mechanism) and the study of the chemical interactions (adsorbate-adsorbent and solvent-adsorbent) using calorimetry tests. Then, the results obtained in both techniques were correlated with the amount of drug adsorbed. The adsorption kinetics of salicylic acid and paracetamol on activated carbons with different oxygen contents could be described with widely kinetic models such as intraparticle, pseudo-first-order, pseudo-second-order, Avrami, and Elovich models; different information about the adsorption mechanism are offered by each of them. The results indicated that the pseudo-first-order rate constant decreases with the molecular size of analgesics and the carboxylic acid groups on the adsorbent surface; the rate constant values are between 0.12 and 2.31 h-1. The adsorbed amount of analgesics and the adsorption rate are greatest on activated carbons with basic characteristics (QRAC 0.45 > 0.24 > 0.21 mmol g-1 for phenol, salicylic acid, and paracetamol, respectively). The enthalpy changes follow the same trend in all activated carbons; for RAC, the results were ΔHimmPHEN = - 33.4 J g-1, ΔHimmSA = - 35.9 J g-1, and ΔHimmPAR = - 45.4 J g-1. The analgesic diffusion rate in the boundary layer increases with the formation of adsorbate-adsorbent interactions (exothermic process).


Comparison of automated systems for the cleaning and disinfection of flexible fibreoptic endoscopes.
A comparison of four cleaning and disinfection machines is described. These varied considerably in design and function and although no single machine possessed all the preferred characteristics, cleaning and disinfection, particularly between patients, was substantially improved. Before purchasing a machine it is recommended that the user ensures that it is convenient to operate, effective in removing soil and bacteria, and adaptable to the range of fibrescopes used within the unit. Infections are often caused by Gram-negative bacilli which are particularly difficult to remove manually from moist narrow channels of the fibrescope and perfusion of all channels including the air channel, is, therefore, recommended. Thorough cleaning and disinfection will not only reduce the likelihood of infection but will also reduce channel blockages and the general deterioration of the fibrescope.


Type-specific screen time associations with cardiovascular risk markers in children.
There is evidence that TV time may have stronger associations with cardiovascular risk markers than other types of screen time, but most studies focus on TV, or total screen time. To examine associations between types of screen time and cardiovascular risk markers in school-age children. Cross-sectional study of 2515 school children in Portugal (aged 2-12 years, data collected in 2009 and 2010). Three types of screen time (TV, electronic games, and PC time) were collected through a questionnaire, and data on three cardiovascular risk markers (resting heart rate; diastolic blood pressure [DBP]; and systolic blood pressure [SBP]) were collected by a trained fieldworker. Complex-samples generalized linear models were run for each combination of screen time predictor and cardiovascular risk outcome, and a clustered cardiovascular risk score, adjusting for potential confounders (including physical activity). Analyses were conducted in 2011 and 2012. TV viewing, but not PC or electronic games time, was associated positively with clustered cardiovascular risk score, DBP, and SBP after adjustment for all covariates. Watching TV for >2 hours/day (compared to <1 hour/day) was associated with higher DBP (coefficient, logged and back-transformed 0.02, 95% CI=0.00, 0.04, linear trend p=0.003); SBP (logged and back-transformed 0.02, 95% CI= -0.01, 0.05, p=0.009), and clustered cardiovascular risk score (0.13, 95% CI=0.02, 0.24, p<0.001). TV viewing, but no other type of screen time, was associated positively with cardiovascular risk markers independently of physical activity. Studies using a single marker of screen time or sedentary behavior may conceal screen time type-specific associations.


Health- and work-related predictors of work disability among employees with a cardiometabolic disease--A cohort study.
The proportion of aging employees with cardiometabolic diseases, such as heart or cerebrovascular disease, diabetes and chronic hypertension is on the rise. We explored the extent to which health- and work-related factors were associated with the risk of disability pension among individuals with such cardiometabolic disease. A cohort of 4798 employees with and 9716 employees without a cardiometabolic disease were followed up for 7years (2005-2011) for disability pension. For these participants, register and survey data (from 2004) were linked to records on disability pensions. Cox proportional hazards modeling was used for estimating the hazard ratios (HR) with 95% confidence intervals (CI). Individuals with heart or cerebrovascular disease had 2.88-fold (95% CI=2.50-3.31) higher risk of all-cause disability pension compared to employees with no cardiometabolic disease. Diabetes was associated with a 1.84-fold (95% CI=1.52-2.23) and hypertension a 1.50-fold (95% CI=1.31-1.72) increased risk of disability pension. Obesity in cases of diabetes and hypertension (15%) and psychological distress in cases of heart or cerebrovascular disease (9%) were the strongest contributing factors. All 12 health- and work-related risk factors investigated accounted for 24% of the excess work disability in hypertension, 28% in diabetes, and 11% in heart or cerebrovascular disease. Cause-specific analyses (disability pension due to mental, musculoskeletal and circulatory system diseases) yielded similar results. In this study, modifiable risk factors, such as obesity and mental comorbidity, predicted permanent exit from the labor market due to disability in individuals with cardiometabolic disease.


Frequency of Celiac Disease and Spontaneous Normalization Rate of Celiac Serology in Children and Adolescent Patients with Type 1 Diabetes
The prevalence of celiac disease (CD) varies between 1% and 10% in patients with type 1 diabetes mellitus (T1DM). This study aimed to determine the frequency of spontaneous recovery of celiac serology and the biopsy-proven CD (BPCD) frequency in patients with T1DM. The data of 668 patients with available celiac serology tests from a total of 779 patients who were followed for the last 10 years with the diagnosis of T1DM were retrospectively evaluated. Positive serology was detected in 103 out of 668 (15.4%) patients. There was spontaneous normalization in 24 (23.3%), fluctuation in 11 (10.7%) and permanently positive serology in 68 (66%). In 46 out of 53 (86.8%) patients with positive serology and biopsy, CD diagnosis was confirmed by biopsy (BPCD). The frequency of BPCD was 6.9%, and the serology in 76.1% was positive at the time of diagnosis of T1DM. The weight, height and body mass index-standard deviation score at diagnosis were lower in patients with BPCD compared to the group without CD. An anti-tissue transglutaminase-IgA (anti-TTG-IgA) level of 11.8 times the upper limit of normal was the most sensitive (93%) and specific (90%) cut-off for BPCD (area under the curve: 0.95; 95% confidence interval: 0.912-1; p<0.001). In our cohort, the frequency of positive serology for CD was 15.4%, while the rate of BPCD was 6.9%. The majority (97.8%) of cases were diagnosed within the first five years of T1DM. In 23.3% of cases, positive anti-TTG-IgA spontaneously resolved without a gluten-free diet (GFD). Therefore, serological follow-up instead of immediate duodenal biopsy or GFD therapy, particularly for patients with asymptomatic and mild anti-TTG IgA level, is warranted.


Minimization of halogenated DBP precursors by enhanced PACl coagulation: The impact of organic molecule fraction changes on DBP precursors destabilization with Al hydrates.
The destabilization of halogenated disinfection-by-product (DBP) precursors by coagulation are mostly subjected to Al speciation of polyaluminum chloride (PACl) and the fraction of dissolved organic matter (DOM), which significantly affect the minimization of halogenated DBP precursors, such as trihalomethane (THM) and haloacetic acids (HAA), in post-chlorination. In this study, the destabilization of DOM in the solution of humic acid (HA) with and without algogenic organic matter (AOM) using two PACl coagulants with different Al speciation was investigated, along with the identification of optical properties for DOM fractions. Additionally, total THM and HAA formation potential of the supernatant before and after coagulation-sedimentation were determined. The results showed that high polymeric Al-containing PACl (PACl-H, 66% Al13) outcompetes in destabilizing HA than commercial PACl (PACl-C, 29% Al13, 32% Al(OH)3). However, the removal of DOM in HA/AOM mixture by both PACl coagulants are significantly suppressed with greater removal of humic-like and fulvic-like substances than aromatic protein-like substances after coagulation-sedimentation, where PACl-C shows superiority in the removal of hydrophobic and hydrophilic substances with MW around 1 kDa than PACl-H. In the absence of AOM, total THM and HAA formation potential were effectively reduced for HA coagulation by both PACl, but vice versa with the presence of AOM, especially for cellular organic matter (COM). Minimization of halogenated DPB precursors by coagulation are predominated by destabilized hydrophilic molecule fractions with Al hydrates. It is concluded that PACl-H favors charge neutralization to destabilize total carbonaceous DBP (C-DBP) precursors in HA or HA/AOM mixture and the corresponding C-DBP formation potential is lower compared to PACl-C that predominates adsorption and co-precipitation in destabilizing C-DBP precursors.


Mapping to obtain EQ-5D utility values for use in NICE health technology assessments.
Quality-adjusted life-years (QALYs) are widely used as an outcome for the economic evaluation of health interventions. However, preference-based measures used to obtain health-related utility values to produce QALY estimates are not always included in key clinical studies. Furthermore, organizations responsible for reviewing or producing health technology assessments (HTAs) may have preferred instruments for obtaining utility estimates for QALY calculations. Where data using a preference-based measure or the preferred instrument have not been collected, it may be possible to "map" or "crosswalk" from other measures of health outcomes. The aims of this study were 1) to provide an overview of how mapping is currently used as reported in the published literature and in an HTA policy-making context, specifically at the National Institute for Health and Clinical Excellence in the United Kingdom, and 2) to comment on best current practice on the use of mapping for HTA more generally. The review of the National Institute for Health and Clinical Excellence guidance found that mapping has been used since first established but that reporting of the models used to map has been poor. Recommendations for mapping in HTA include an explicit consideration of the generalizability of the mapping function to the target sample, reporting of standard econometric and statistical tests including the degree of error in the mapping model across subsets of the range of utility values, and validation of the model(s). Mapping can provide a route for linking outcomes data collected in a trial or observational study to the specific preferred instrument for obtaining utility values. In most cases, however, it is still advantageous to directly collect data by using the preferred utility-based instrument and mapping should usually be viewed as a "second-best" solution.


Lupus vulgaris mimicking hemangioma diagnosed 42 years after onset: a case report.
Lupus vulgaris is the most common form of cutaneous tuberculosis. It may easily be overlooked if a proper differential diagnosis is omitted. A 46-year-old Turkish woman presented with a 42-year history of erythamatous plaque on her left arm. Ziehl-Neelsen and periodic acid-Schiff stains did not show any acid-fast bacilli. Culture from a biopsy specimen was negative for Mycobacterium tuberculosis. The result of a polymerase chain reaction-based assay for Mycobacterium was negative. Histopathologic findings revealed a tuberculoid granuloma containing epithelioid cells, lymphocytes and Langerhans-type giant cells. A diagnosis of lupus vulgaris was made by clinical and histopathologic findings. The lesion improved after antituberculous therapy, confirming the diagnosis of lupus vulgaris.


The de-adoption of innovative mental health practices (IMHP): why organizations choose not to sustain an IMHP.
The de-adoption or discontinuance of innovative mental health practices (IMHPs) was investigated among twelve mental health providers in Ohio. Researchers used mixed methodology to investigate factors that led the organizations to de-adopt the IMHPs. Findings suggest at least five indicators that an organization is likely to discontinue an IMHP (e.g., lack of financial resources and problems related to attracting and retaining qualified staff). Adopting agencies, state and local mental health authorities, and external technical assistance groups may be able to use this information to assist organizations in continuing with the implementation process.


Power transmission along biological membranes.
Hypothesis on long-distance power transmission along extended energy-transducing membranes (Skulachev, 1969, 1971, 1980), has been experimentally proven in four different systems, namely, (i) trichomes of filamentous cyanobacterium Phormidium uncinatum; (ii) filamentous mitochondria and mitochondrial network in fibroblasts; (iii) clusters of roundish heart muscle mitochondria interconnected with mitochondrial junctions; (iv) mixed animal cell cultures interconnected with gap junctions. In all cases, energy was shown to be transmitted in the form of a transmembrane electric potential difference. The transmission occurred for distances as long as several tens of micrometers. Since the (a) delta-muH-bearing cytoplasmic membrane of cyanobacteria and the inner mitochondrial membrane and (b) delta-muNa-bearing outer animal cell membrane were found to be competent in such an effect, one may assume that the power transmission is a fundamental function of extended membrane systems. This mechanism can be used at the intracellular level (mitochondrial) as well as at the supracellular level (cytoplasmic and outer cell membranes). Studies on the possible involvement of membranes in lateral transport of oxygen, ions, fatty acids and membrane proteins seem to hold good promise.


Visualization of the vidian canal and nerve using magnetic resonance imaging.
Few studies have investigated the vidian nerve (VN) and vidian canal (VC) with the use of magnetic resonance imaging (MRI). The present study aimed to characterize the VC and VN using MRI. A total of 91 patients underwent thin-sliced, contrast MRI. The course of the VC and VN and the relationships with relevant structures were analyzed. The VC was identified in 95% of axial images on the right side and in 93% on the left. The course of the VC was delineated in 99% of serial coronal images on both sides. The VN location in the VC was highly variable. The course of the VC and transmitting VN was delineated in 95% of sagittal images on the right side and in 91% on the left. The mean length of the VC was 19.8 mm on the right side and 19.3 mm on the left. Topographical relationships between the anterior genu of the petrous internal carotid artery and the posterior end of the vidian canal could be classified into three types. Of these, the type terminating at the level of the petrous carotid was the most predominant, comprising 76% of 182 sides. The course of the VC and transmitting VN could be classified into four types. The straight type was the most predominant and was found in 41%. The VC and transmitting VN are structures with variable morphologies. Contrast MRI is useful for delineating the VC and VN.


Exploring electronic cigarette portrayals: a content and thematic analysis of African online news coverage.
Electronic cigarette use has surged internationally in recent years, with numerous countries noting an uptick in users. Despite this, the portrayal of e-cigarette usage in African news remains unclear. This research investigates the subject, employing a mixed-methodology approach. The study units were news articles on electronic cigarette use retrieved from AllAfrica, an online African news archive. A total of 38 online news and opinion articles published between June 2017 and June 2022 qualified the exclusion and inclusion criteria. A content analysis revealed prevalent codes and themes, while a thematic analysis explored the association between news sources and framing. The results indicate that articles and arguments presenting e-cigarettes positively outnumber those with a negative slant. The health impacts of electronic cigarettes emerged as the most discussed topic, with health authorities frequently cited as news sources. However, these health authorities often lacked a unified stance on e-cigarette safety. The lack of consensus among health officials could have public health consequences, possibly resulting in the formulation of uninformed policies.


Pituitary adrenal recovery following short-term suppression with corticosteroids.
To provide clinical guidelines for the use of high-dose short-term glucocorticoid therapy, we studied recovery of the hypothalamic-pituitary-adrenal axis in 10 normal men following the administration of suppressive doses of prednisone (25 mg twice daily for five days). Cortisol responses to insulin-induced hypoglycemia and synthetic ACTH before treatment were compared with responses two and five days after concluding the prednisone course when adrenal function was not influenced by the presence of exogenous steroid. Two days after prednisone therapy, peak cortisol responses to both hypoglycemia (11.0 +/- 0.9 microgram/dl mean +/- SEM) and synthetic ACTH (13.3 +/- 1.4 microgram/dl) were significantly reduced compared to pretreatment (20.6 +/- 1.6 and 27.3 +/- 2.5 microgram/dl, respectively, p less than 0.001). Five days after concluding the prednisone therapy, peak cortisol response to hypoglycemia had returned to near pretreatment levels although peak cortisol response in the adrenal gland to synthetic ACTH (22.3 +/- 1.1 microgram/dl) remained reduced (p less than 0.05). These data suggest that brief courses of high-dose prednisone therapy may limit the adrenal component of the hypothalamic-pituitary-adrenal response to stress for up to five days.


Kinetic of body nitrogen loss during a whole day infusion and withdrawal of glucose and insulin in injured patients.
To investigate the kinetics of body nitrogen (N) excretion during 24 h glucose infusion (relating glycemia with insulin supply) and during subsequent 24 h saline infusion in injured patients during a full blown stress reaction. To define the lag time between the start of the withdrawal of glucose and insulin infusion, and the modification in the N loss from the body, and the time span to reach the maximum effect and its size. The knowledge of these variables is mandatory to plan short term studies in critically ill patients, while assuring the stability of the metabolic condition during the study period, and also to assess the possible weaning of the effect on protein breakdown during prolonged glucose and insulin infusion. 24-36 h after injury, patients were fasted ( < 100 g glucose) for 24 h (basal day). Thereafter, a 24 h glucose infusion in amount corresponding to measured fasting energy production rate (EPR), clamping glycemia at normal level with insulin supply followed by 24 h saline infusion, was performed. Total N, urea and 3-methyl-histidine (3-MH) in urine were measures on 4 h samples starting from 20th h of the basal day. Multipurpose ICU in University Hospital. 6 consecutive patients who underwent accidental and/or surgical injury, immediately admitted for respiratory assistance (FIO2 < 0.04). Excluded patients were those with abnormal nutritional status, cardiovascular compromise and organ failures. Patients showed a 33% increase in measured versus predicted fasting EPR and a consistent increase in N and 3-MH urinary loss. An infusion of glucose at 5.95 +/- 0.53 mg/kg x min (97.20 +/- 0.03% of the fasting measured EPR) with 1.22 +/- 0.18 mU/kg x min insulin infusion reduced N and 3-MH loss after a time lag of 12 h. The peak decrease in body N (-36%) and 3-MH loss (-38%) was reached during the first 12 h of glucose withdrawal period. Thereafter, during the following 12 h, the effect completely vanished confirming that it is therapy-dependent and that the metabolic environment of the patients did not change during the three days study period. 24 h glucose withdrawal reduces N and 3-MH loss injured patients, the drug-like effect is maintained during the first 12 h of withdrawal and thereafter disappears. The study suggests that at least a 24 h study period is necessary when planning studies exploring energy-protein metabolism relationship in injured patients, and, again 24 h before changing protocol in a crossover study.


Histaminelike immunoreactive neurons innervating putative neurohaemal areas and central neuropil in the thoraco-abdominal ganglia of the flies Drosophila and Calliphora.
The fused thoraco-abdominal ganglia of the flies Calliphora vomitoria and Drosophila melanogaster were investigated immunocytochemically with antisera against histamine. In both insect species, 18 histaminelike immunoreactive (HA-IR) neurons were resolved in these ganglia. Six of these neurons have cell bodies in the thoracic neuromeres and 12 in the fused abdominal neuromeres. All cell bodies are situated ventrally. In Calliphora all cell bodies are arranged in a segmental pattern. In Drosophila only the thoracic cell bodies have a segmental arrangement, whereas the abdominal ones are clustered anteriorly close to the last thoracic neuromere. In both species the six thoracic neurons supply processes to the synaptic neuropil in the thoracic neuromeres and to the dorsal neural sheath. The processes in the neural sheath run anteriorly in the lateral portions of the ganglion into the cervical connective. In a few regions laterally arborizing terminals are found in putative neurohaemal areas. These areas were investigated by electron microscopic immunocytochemistry in Calliphora. The HA-IR terminals (containing small granular vesicles) were found outside the "blood-brain barrier" below the acellular basal lamina of the neural sheath. Release of histamine into the circulation is therefore theoretically possible. The central processes of the six thoracic HA-IR neurons may interact synaptically with large numbers of other neurons in the neuropil, and the peripheral varicose fibers from the same HA-IR neurons possibly are neurohaemal release sites. The abdominal HA-IR neurons, in contrast, form extensive arborizations within the synaptic neuropil only. Both thoracic and abdominal neurons have ipsilateral and contralateral branches as well as processes that invade more than one neuromere. A single HA-IR neuron thus invades large volumes of synaptic neuropil. Histamine may be used by neurons of the ventral ganglia both as neurotransmitter (or neuromodulator) and as a circulating neurohormone released from the neural sheath.


Isolation of a tumor-associated transplantation antigen (TATA) from an SV40-induced sarcoma. Resemblance to the TATA of chemically induced neoplasms.
A tumor rejection antigen (TATA), obtained from the cytosol of a BALB/c mKSA sarcoma induced by SV40 virus, has been partially purified. This partially purified antigen is strikingly immunogenic against mKSA, providing more than 90% inhibition of growth at levels of 10-30 micrograms. This antigen preparation does not protect against challenge with another SV40-induced BALB/c sarcoma VLM which, however, shares a group-specific TATA with mKSA. The antigen also does not immunize against challenge with the methylcholanthrene-induced sarcomas of BALB/c mice, Meth A, CI-4, CII-7 and CII-10, each of which has its own unique TATA. Binding assays, using ELISA, failed to detect any SV40 antigen in the antigen preparation despite the fact that the large T antigen of SV40 (or fragments of it) constitutes the immunodominant TATA of mKSA.


Participatory mapping to address neighborhood level data deficiencies for food security assessment in Southeastern Virginia, USA.
Food is not equitably available. Deficiencies and generalizations limit national datasets, food security assessments, and interventions. Additional neighborhood level studies are needed to develop a scalable and transferable process to complement national and internationally comparative data sets with timely, granular, nuanced data. Participatory geographic information systems (PGIS) offer a means to address these issues by digitizing local knowledge. The objectives of this study were two-fold: (i) identify granular locations missing from food source and risk datasets and (ii) examine the relation between the spatial, socio-economic, and agency contributors to food security. Twenty-nine subject matter experts from three cities in Southeastern Virginia with backgrounds in food distribution, nutrition management, human services, and associated research engaged in a participatory mapping process. Results show that publicly available and other national datasets are not inclusive of non-traditional food sources or updated frequently enough to reflect changes associated with closures, expansion, or new programs. Almost 6 percent of food sources were missing from publicly available and national datasets. Food pantries, community gardens and fridges, farmers markets, child and adult care programs, and meals served in community centers and homeless shelters were not well represented. Over 24 km2 of participant identified need was outside United States Department of Agriculture low income, low access areas. Economic, physical, and social barriers to food security were interconnected with transportation limitations. Recommendations address an international call from development agencies, countries, and world regions for intervention methods that include systemic and generational issues with poverty, incorporate non-traditional spaces into food distribution systems, incentivize or regulate healthy food options in stores, improve educational opportunities, increase data sharing. Leveraging city and regional agency as appropriate to capitalize upon synergistic activities was seen as critical to achieve these goals, particularly for non-traditional partnership building. To address neighborhood scale food security needs in Southeastern Virginia, data collection and assessment should address both environment and utilization issues from consumer and producer perspectives including availability, proximity, accessibility, awareness, affordability, cooking capacity, and preference. The PGIS process utilized to facilitate information sharing about neighborhood level contributors to food insecurity and translate those contributors to intervention strategies through discussion with local subject matter experts and contextualization within larger scale food systems dynamics is transferable.


Sepiapterin reductase in human amniotic and skin fibroblasts, chorionic villi, and various blood fractions.
Sepiapterin reductase activity has been measured in amniotic fibroblasts by two procedures: one photometric and the other HPLC-fluorimetric. Both can be used for quantitative measurements, but the latter has considerable advantages including smaller standard deviation, much lower detection limit, and less volume of sample required. Sepiapterin reductase activity was also assayed in skin fibroblasts, chorionic villi and various blood fractions including stimulated mononuclear blood cells. Red blood cells have a low specific activity compared to unstimulated mononuclear blood cells, although the latter have a mean value with a high standard deviation. When the mononuclear blood cells were cultured for 5 days, the mean specific activity increased and the range became tighter. Enzyme stability and N-acetylserotonin inhibition were also studied.


Evaluation of nasal patency by fiberoptic rhinoscopy.
A novel method of assessing anterior nasal patency by flexible fiberoptic rhinoscopy was evaluated in two centers by comparison with active anterior rhinomanometry. Rhinoscopy and rhinomanometry were performed 20 times on each of 14 subjects during 14 to 26 minutes. The procedure was videotaped, and nasal airway area was measured from a video monitor. The mean coefficients of variation for rhinoscopy and rhinomanometry were 14% and 19%, respectively. Another investigator examined five subjects by rhinoscopy 30 times in 15 minutes; the mean coefficient of variation was 9%. These means were not significantly different. Rhinoscopy and rhinomanometry were performed at 30-minute intervals for a 6-hour period in 13 subjects. Three investigators independently evaluated results for changes in nasal function characteristic of the nasal cycle. Rhinoscopy detected the nasal cycle in an average of 72% of subjects and rhinomanometry in 49%. Both methods detected the response to topically applied oxymetazoline and methacholine. Results indicate that, whereas the two procedures evaluate different aspects of nasal function, their precision is similar. Rhinoscopy additionally permits evaluation of nasal mucosal changes occurring from disease or treatment.


Clinicopathological correlation between expression of PTHrP receptor and various prognostic factors in breast cancer without axillary lymph node metastasis.
Expression of PTHrP is immunohistologically found in mammary tissues of all the normal cell, hyperplasia and malignant cell. In patients of breast cancer, positive ratio of PTHrP is reportedly 60-69%. Higher positive ratios of PTHrP are found in breast cancer showing bone metastasis than those without bone metastasis. And, breast cancer patients with PTHrP positive show poor prognosis suggesting a relationship to histological grade. Regarding PTHrP receptor, there is few report on its physiological role and relationship to other prognostic factors. The aim of this study was to determine the correlation between PTHrP receptor and various prognostic parameters of breast cancer patients with no axillary node metastasis. We employed 26 breast cancer patients, who showed negative axillary node metastasis and did not receive postoperative therapy. We examined relationship between PTHrP receptor and various prognostic factors such as hormone receptors, MIB-1 index, proliferation of cell nuclear antigen (PCNA), DNA ploidy, S-phase fraction, age, tumor diameter, c-erbB-2, and Cathepsin D. No relationship between expression of PTHrP receptor and the cancer recurrence. PTHrP receptor correlated MIB-1 index alone (p < 0.044). This findings suggest PTHrP receptor is related to the tumor proliferation of breast cancer.


MKP3 eliminates depolarization-dependent neurotransmitter release through downregulation of L-type calcium channel Cav1.2 expression.
Release of neurotransmitters is a fundamental and regulated process that is essential for normal brain functioning. Regulation of this process is potentially important for any neuronal process, and disruption of the release process may contribute to the pathophysiology associated with psychiatric diseases. In this work it is shown that expression of the negative regulator of mitogen-activated protein kinase (MAPK) signaling the MAPK phosphatase MKP3/DUSP6 eliminates depolarization-dependent release of dopamine in rat PC12 cells. Pharmacologic interventions with latrotroxin (LTX) or A23187, which make the cells permeable to calcium, reestablish the dopamine release. Calcium imaging also reveals that calcium influx is impaired in MKP3-expressing cells. Because acute pharmacologic inhibition of MAPKs has no effect on dopamine release in naïve PC12 cells, the MKP3-mediated elimination of neurotransmitter release must be caused by a long-term process, such as changes in gene expression. In support of this the expression of the L-type calcium channel cav1.2 alpha subunit (Cacna1c) is decreased in MKP3-expressing PC12 cells. With the reintroduction of cav1.2 expression, neurotransmitter release is restored in the MKP3-expressing PC12 cells. Thus, MKP3 expression reduces neurotransmitter release by decreasing the expression of cav1.2. Because MKP3 is increased when neuronal activity is elevated, this process could play a role in regulating neurotransmitter homeostasis.


HIV-1 infection in HIV-1 enzyme-linked immunoassay seronegative patients in Kinshasa, Zaire.
Serum samples of 62 African patients who had clinical manifestations of HIV-1 infection but were seronegative for HIV-1 by ELISA (Organon) were subsequently further tested by another HIV-1 ELISA test (Wellcozyme), HIV-1 IgG Western blot, HIV-1 antigen detection and HIV-2 ELISA. Patients' lymphocytes were cultured for HIV-1 and 2. Because of limited quantities of serum available all tests were not performed on all samples. Seven (26%) of 27 sera of patients meeting the WHO clinical case definition of AIDS were Western-blot-positive. In contrast, of 35 patients' sera with possible HIV related disease, only one (3%) was Western blot positive (P = 0.02) and none of 75 sera from HIV-1 ELISA (Organon) seronegative blood donors (P less than 0.01) were Western blot positive. Of 30 HIV-1 ELISA (Organon) seronegative patients tested with the HIV-1 ELISA Wellcozyme assay only one was seropositive (this patient's serum was also Western blot positive). Of 17 HIV-1 ELISA (Organon) seronegative patients tested, HIV-1 antigen was found in 1 case (6%) (this patient's serum was Western blot negative). None of the 34 patients tested by HIV-2 serology was HIV-2 seropositive. HIV-1 was isolated by culture in 3 (21%) of 14 HIV-1 ELISA seronegative patients (sera of the 3 patients were Western blot negative). In total, 12 (19%) of 62 HIV-1 ELISA (Organon) seronegative patients were found to be positive for HIV, either by Western blot HIV antigen testing or viral culture.(ABSTRACT TRUNCATED AT 250 WORDS)


Olfactory dysfunction in frontotemporal dementia and psychiatric disorders: A systematic review.
Frontotemporal dementia (FTD) is a progressive neurodegenerative disease. Diagnosis of FTD, especially the behavioural variant, is challenging because of symptomatic overlap with psychiatric disorders (depression, schizophrenia, bipolar disorder). Olfactory dysfunction is common in both FTD and psychiatric disorders, and often appears years before symptom onset. This systematic review analysed 74 studies on olfactory function in FTD, depression, schizophrenia and bipolar disorder to identify differences in olfactory dysfunction profiles, focusing on the most common smell measures: odour identification and discrimination. Results revealed that FTD patients were severely impaired in odour identification but not discrimination; in contrast, patients diagnosed with schizophrenia showed impairments in both measures, while those diagnosed with depression showed no olfactory impairments. Findings in bipolar disorder were mixed. Therefore, testing odour identification and discrimination differentiates FTD from depression and schizophrenia, but not from bipolar disorder. Given the high prevalence of odour identification impairments in FTD, and that smell dysfunction predicts neurodegeneration in other diseases, olfactory testing seems a promising avenue towards improving diagnosis between FTD and psychiatric disorders.


Accuracy and response-time distributions for decision-making: linear perfect integrators versus nonlinear attractor-based neural circuits.
Animals choose actions based on imperfect, ambiguous data. "Noise" inherent in neural processing adds further variability to this already-noisy input signal. Mathematical analysis has suggested that the optimal apparatus (in terms of the speed/accuracy trade-off) for reaching decisions about such noisy inputs is perfect accumulation of the inputs by a temporal integrator. Thus, most highly cited models of neural circuitry underlying decision-making have been instantiations of a perfect integrator. Here, in accordance with a growing mathematical and empirical literature, we describe circumstances in which perfect integration is rendered suboptimal. In particular we highlight the impact of three biological constraints: (1) significant noise arising within the decision-making circuitry itself; (2) bounding of integration by maximal neural firing rates; and (3) time limitations on making a decision. Under conditions (1) and (2), an attractor system with stable attractor states can easily best an integrator when accuracy is more important than speed. Moreover, under conditions in which such stable attractor networks do not best the perfect integrator, a system with unstable initial states can do so if readout of the system's final state is imperfect. Ubiquitously, an attractor system with a nonselective time-dependent input current is both more accurate and more robust to imprecise tuning of parameters than an integrator with such input. Given that neural responses that switch stochastically between discrete states can "masquerade" as integration in single-neuron and trial-averaged data, our results suggest that such networks should be considered as plausible alternatives to the integrator model.


Lateral supraorbital approach applied to tuberculum sellae meningiomas: experience with 52 consecutive patients.
Various surgical approaches for the removal of tuberculum sellae meningiomas (TSMs) have previously been described. To assess the reliability and safety of the lateral supraorbital (LSO) approach to remove TSMs. We identified all TSM patients operated on at the Department of Neurosurgery at Helsinki University Central Hospital, Finland, by the senior author (J.H.) using the LSO approach between September 1997 and August 2010. We retrospectively analyzed the clinical data, radiological findings, surgical treatment, histology, and outcome of patients and discuss the operative technique. Apparent complete tumor removal was achieved in 45 patients (87%). Of 42 patients, preexisting visual deficit improved in 22, remained the same in 13, and worsened in 7, and de novo visual deficit occurred in 1 patient. At 3 months post-discharge, 47 patients (90%) had a good recovery, 4 (8%) were moderately disabled, and 1 (2%) died 40 days after surgery of unexplained cardiac arrest. Seven patients (13%) had minimal residual tumors, 2 of which required reoperation. During the median follow-up of 59 months (range, 1-133 months), tumor recurred in 1 of the patients who had undergone a second operation. TSMs of all sizes can be removed via the LSO approach with minimal morbidity and mortality. Low-power or no coagulation is recommended near the optic nerves and the optic chiasm to preserve their vascular support from the internal carotid artery perforators. Our results are comparable to those obtained using more extensive and time-consuming approaches. We recommend the LSO approach to remove TSMs.


Adverse prognosis of epigenetic inactivation in RUNX3 gene at 1p36 in human pancreatic cancer.
Alteration in transforming growth factor-beta signalling pathway is one of the main causes of pancreatic cancer. The human runt-related transcription factor 3 gene (RUNX3) is an important component of this pathway. RUNX3 locus 1p36 is commonly deleted in a variety of human cancers, including pancreatic cancer. Therefore, we examined genetic and epigenetic alterations of RUNX3 in human pancreatic cancer. Thirty-two patients with pancreatic cancer were investigated in this study. We examined the methylation status of RUNX3 promoter region, loss of heterozygosity (LOH) at 1p36, and conducted a mutation analysis. The results were compared with clinicopathological data. Promoter hypermethylation was detected in 20 (62.5%) of 32 pancreatic cancer tissues, confirmed by sequence of bisulphite-treated DNA. Loss of heterozygosity was detected in 11 (34.3%) of 32 pancreatic cancers. In comparison with clinicopathological data, hypermethylation showed a relation with a worse prognosis (P=0.0143). Hypermethylation and LOH appear to be common mechanisms for inactivation of RUNX3 in pancreatic cancer. Therefore, RUNX3 may be an important tumour suppressor gene related to pancreatic cancer.


Arousal induced by injection of triazolam into the dorsal raphe nucleus of rats.
In order to explore the possible sites at which benzodiazepines alter sleep, we have performed sleep studies following administration of 0.5 microgram of triazolam into the dorsal raphe nucleus of rats. Triazolam significantly increased sleep latency and decreased non-rapid eye movement (REM) sleep, with an effect greatest in the first 2 hours after injection. Total REM sleep time was not significantly affected, although there was a modest trend toward reduction in the first 2 hours. In contrast to the decreased sleep resulting from injection into the dorsal raphe nucleus, triazolam did not significantly alter sleep in animals in whom it was injected into surrounding areas. Similarly, the low dose employed in this study did not significantly affect sleep when injected into the lateral ventricle. These data are reminiscent of studies showing transient decreases in sleep following lesions of the dorsal raphe nucleus.


Will polycentric cities cause more CO2 emissions? A case study of 232 Chinese cities.
From 2000 to 2010 China experienced rapid economic development and urbanization. Many cities in economically developed areas have developed from a single-center status to polycentricity. In this study, we used exploratory spatial data analysis (ESDA) to identify the population centers, which identified 232 cities in China as having urban centers. COMP was used to represent urban agglomeration, and POLYD (representing how far is the city's sub-centers to the main center), POLYC (representing the number of a city's centers), and POLYP (representing the population distributed between the main center and the sub-centers) were used to indicate urban polycentricity. Night light data were used to determine the CO2 emissions from various cities in China. A mixed model was used to study the impact of urban aggregation and polycentric data on the CO2 emission efficiency in 2000 and 2010. The study found that cities with higher compactness were distributed in coastal areas, and the cities with higher multicentricity were distributed in the Yangtze River Delta and Shandong Province. The more compact the city was, the less conducive it was to improving CO2 emission efficiency. Polycentric development of the city was conducive to improving the CO2 emission efficiency, but the number of urban centers had no significant relationship with the CO2 emission efficiency. Our research showed that the compactness and multicentricity of the city had an impact on the CO2 emission efficiency and provided some planning suggestions for the low carbon development of the city.


Axl promotes cell invasion by inducing MMP-9 activity through activation of NF-kappaB and Brg-1.
Activity of the Axl receptor tyrosine kinase is positively correlated with tumor metastasis; however, its detailed role in the mechanism of tumor invasion is still not completely understood. Here, we show that Axl enhances the expression of matrix metalloproteinase 9 (MMP-9), required for Axl-mediated invasion both in vitro and in vivo. We found that the highly selective MEK1/2 inhibitors U0126 and PD98059, and the expressed dominant-negative form of extracellular signal-regulated kinase (ERK), completely block Axl-mediated MMP-9 activation. In contrast, the phosphatidylinositol 3-kinase inhibitor LY294002 and wortmannin had little effect on activation. Interestingly, however, the Axl ligand Gas6 is not involved in Axl-mediated MMP-9 activation. Mutation of Glu59(Axl) and Thr77(Axl) dramatically reduced Gas6-Axl binding but continued to induce MMP-9 activation. In addition, overexpression of Axl-activated ERK and enhanced nuclear factor-kappaB (NF-kappaB) transactivation and brahma-related gene-1 (Brg-1) translocation. Exposure to the NF-kappaB inhibitor silibinin, which inhibits IkappaBalpha kinase activity, or overexpression of the dominant-negative mutant IkappaB and Brg-1 strikingly inhibited Axl-mediated MMP-9 activation. These data indicate that coordination of ERK signaling and NF-kappaB and Brg-1 activation are indispensable to regulation of Axl-dependent MMP-9 gene transcription. Together with previous data, our results provide a plausible mechanism for Axl-mediated tumor invasion and establish a functional link between the Axl and MMP-9 signaling pathways.


Insight into the short- and long-term effects of inorganic phosphate on anammox granule property.
The short- and long-term effects of inorganic phosphate on property of anaerobic ammonium oxidation (anammox) granule were investigated in this study. Acute exposure to high-level phosphate (⩾50 mM) induced the cytoplasm leakage. During a 195-day continuous-flow operation, the gradually increasing phosphate (up to 500 mgP L(-1)) slightly affected the specific anammox activity, hardly impacted the heme c content, remarkably decreased the extracellular polymeric substances production and significantly stimulated the dehydrogenase activity of anammox granules. Microbial community analysis showed no shift in the dominant anammox strain and higher population but lower relative abundance of anaerobic ammonium-oxidizing bacteria compared to the control granules. Interestingly, novel anammox granules with a hydroxyapatite core were cultivated, which possessed excellent settleability, huge granule diameter and superior mechanical strength. This study supported the application of granule-based anammox process as a pre-processing treatment in phosphate-containing and ammonia-rich wastewaters.


Spatial landscape model to characterize biological diversity using R statistical computing environment.
Due to urbanization and population growth, the degradation of natural forests and associated biodiversity are now widely recognized as a global environmental concern. Hence, there is an urgent need for rapid assessment and monitoring of biodiversity on priority using state-of-art tools and technologies. The main purpose of this research article is to develop and implement a new methodological approach to characterize biological diversity using spatial model developed during the study viz. Spatial Biodiversity Model (SBM). The developed model is scale, resolution and location independent solution for spatial biodiversity richness modelling. The platform-independent computation model is based on parallel computation. The biodiversity model based on open-source software has been implemented on R statistical computing platform. It provides information on high disturbance and high biological richness areas through different landscape indices and site specific information (e.g. forest fragmentation (FR), disturbance index (DI) etc.). The model has been developed based on the case study of Indian landscape; however it can be implemented in any part of the world. As a case study, SBM has been tested for Uttarakhand state in India. Inputs for landscape ecology are derived through multi-criteria decision making (MCDM) techniques in an interactive command line environment. MCDM with sensitivity analysis in spatial domain has been carried out to illustrate the model stability and robustness. Furthermore, spatial regression analysis has been made for the validation of the output.


Posterior inferior cerebellar artery with extracranial origin harboring an extracranial aneurysm.
We report on a rare case of a saccular aneurysm on the TM segment of the right PICA. The aneurysm was located at the nonbifurcation region of the PICA. The patient underwent a brain CT scan that revealed a diffuse SAH and an IVH in the fourth ventricle with obstructive hydrocephalus. After external ventricular drainage to relieve the hydrocephalus, the aneurysm was demonstrated by cerebral digital subtraction angiography. The origin of the PICA aneurysm was extracranial and intradural, illustrating a rare location of such type of aneurysm.