Dental insurance and dental care among working-age adults: differences by type and complexity of disability.
People with disabilities experience barriers to dental care, which may vary depending on type of disability and disability complexity (e.g., impact on activities of daily living). The purpose of this study was to examine differences in dental insurance, receipt of dental checkups, and delayed and unmet needs for dental care by type and complexity of disability. We conducted cross-sectional analysis of 2002-2011 data from the Medical Expenditure Panel Survey. Multivariable logistic regression analyses compared adults ages 18-64 in five disability type groups (physical, cognitive, vision, hearing, or multiple disabilities) to those with no disabilities, and compared people with complex activity limitations to those without complex limitations. All disability types except hearing had significantly higher adjusted odds of being without dental insurance, as did people with complex activity limitations. All disability groups except those with cognitive disabilities had increased odds of receiving dental checkups less than once a year. Similarly, all disability groups were at increased risk of both delayed and unmet needs for dental care. Odds ratios were generally highest for people with multiple types of disabilities. There are significant disparities in having dental insurance and receiving dental care for adults with disabilities, especially those with multiple types of disabilities, after controlling for socioeconomic and demographic differences. Further, disparities in care were apparent even when controlling for presence of dental insurance.


Tumor-associated macrophages and anti-tumor therapies: complex links.
Myeloid cells infiltrating the tumor microenvironment, especially tumor-associated macrophages (TAMs), are essential providers of cancer-related inflammation, a condition known to accelerate tumor progression and limit the response to anti-tumor therapies. As a matter of fact, TAMs may have a dual role while interfering with cancer treatments, as they can either promote or impair their functionality. Here we review the connection between macrophages and anticancer therapies; moreover, we provide an overview of the different strategies to target or re-program TAMs for therapeutic purposes.


The impacts of acid suppression on duodenal microbiota during the early phase of severe acute pancreatitis.
Duodenal dysbiosis may be potential infection risks in patients with severe acute pancreatitis (SAP). Acid-suppression drugs (ACDs) are widely used in SAP patients in Asian countries. However, the impact of ACDs on duodenal microbiota during the early phase of SAP is still unknown. This randomized controlled clinical trial evaluated the impacts of esomeprazole (Eso), one of ACDs on duodenal microbiota during the first week of SAP with duodenal aspirates culture and 16sRNA Illumina sequencing analysis. 66 patients were randomized as 1:1 ratio into Eso group (Eso 40 mg/day) and Eso-N group (no Eso). The occurrence of duodenal bacterial overgrowth (DBO) was significantly higher in Eso group (about 85%) than that in Eso-N group (about 42%). The duodenal microbiota of the SAP patients shifted away from that of the normal control. There were differences between the Eso-N and Eso groups including enriched abundances of the class Negativicutes, order Selenomonadales and genus Veillonella. Acid suppression significantly increased incidence of Candida oesophagitis (CE) by 8-folds but did not increase other infectious events. In conclusion, acid suppression greatly increased the occurrence of DBO, duodenal dysbiosis and CE during the first week of SAP. Restrictive use of acid-suppressing medications might be helpful to reduce CE and potential risk of pancreatic infection in SAP patients.Trial registration: Chictr.org, ChiCTR-IPR-16008301, Registered April 18 2016, http://www.chictr.org.cn/showproj.aspx?proj=14089 .


Interactions of carbamazepine, chlormethiazole and pentobarbitone with adenosine on hippocampal slices.
1. The effects of the anticonvulsants carbamazepine, chlormethiazole and pentobarbitone and their interactions with adenosine have been studied in rat hippocampal slices. 2. Neither chlormethiazole nor pentobarbitone changed the evoked population spike in CA1 stratum pyramidale, while carbamazepine produced a gradual decline of this potential at concentrations of 100 microM or greater. 3. This effect was not prevented by 8-phenyltheophylline. 4. Only carbamazepine (greater than 20 microM) produced any change of adenosine responses: a slowly developing reduction of the inhibitory action. 5. None of the anticonvulsants altered responses to the amino acid excitant N-methyl-aspartate, or kynurenic acid.


Neurochemical evidence for tryptaminergic ascending and descending pathways in the spinal cord of the dog.
The brain and spinal cord of the chronic spinal dog contained higher levels of tryptamine than comparable regions of the intact dog. The most significant brain elevations were found in the cerebellum and mesencephalon. Further, tryptamine in the white matter of the spinal cord above the level of transection was higher than below. These findings have been interpreted as indicating that there are tryptaminergic pathways descending in the white matter of the spinal cord from the mesencephalon, cerebellum and rostral spinal cord. The level of tryptamine below the transection was not different from that found in the intact dog, suggesting that there are not only descending but ascending tryptaminergic pathways and that when the axons are transected. tryptamine accumulates proximal to the level of transection.


In Situ Hydrolysis of Block Copolymers at the Water-Oil Interface.
In situ manipulation of the chemical composition of block copolymers at the fluid interfaces affords a route by which the interfacial tension, the packing of the copolymers, and the penetration of the blocks into the two liquids can be controlled. Here, a series of linear block copolymers of poly(solketal methacrylate-b-styrene) (PSM-b-PS) are used, converting hydrophobic PSM block into a hydrophilic glycerol monomethacrylate (GM) block, that results in a marked decrease in the liquid-liquid interfacial tension. The kinetics of the first-order hydrolysis reaction was analyzed by monitoring the time-dependent interfacial tension as a function of pH, polymer concentration, molecular weight, and composition. Fluorescence recovery after photobleaching (FRAP) was used to measure the in-plane dynamics of the copolymers before and after hydrolysis. This work provides insights into a quantitative pathway by which in situ interfacial reactions may be performed and monitored in real time, completely changing the interfacial activity of the molecule.


Light-chain cardiac amyloidosis for the non-expert: pearls and pitfalls.
Cardiac amyloidosis (CA) is an uncommon, progressive, and fatal disease; the two main forms that can affect the heart are transthyretin CA and light chain CA (AL-CA). AL-CA is a medical urgency for which a diagnostic delay can be catastrophic for patients' outcome. In this manuscript, we focus on the pearls and pitfalls that are relevant to achieve a correct diagnosis and to avoid diagnostic and therapeutical delays. Through the aid of three unfortunate clinical cases, some fundamental diagnostic aspects are addressed, including the following: first, a negative bone scintigraphy does not exclude CA, with patients with AL-CA frequently showing no or mild cardiac uptake, and its execution should not delay hematological tests; second, fat pad biopsy does not have a 100% sensitivity for AL amyloidosis and, if negative, further investigations should be performed, particularly if the pre-test probability is high. Third, Congo Red staining is not sufficient to reach a definitive diagnosis and amyloid fibrils typing with mass spectrometry, immunohistochemistry, or immunoelectron microscopy is crucial. To achieve a timely and correct diagnosis, all the necessary investigations must be performed, always considering the yield and diagnostic accuracy of each examination.


Penile fracture with isolated corpus spongiosum injury.
Penile fractures are classically described as presenting with rapid detumescence of an erection associated with blunt trauma. This clinical finding is due to a tear in the tunica albuginea surrounding the corpora cavernosum. We, however, present the case of a patient who presented with a 'classical' penile fracture but was found on surgical exploration to only have an isolated corpus spongiosum injury.


MEDXVIEWER: PROVIDING A WEB-ENABLED WORKSTATION ENVIRONMENT FOR COLLABORATIVE AND REMOTE MEDICAL IMAGING VIEWING, PERCEPTION STUDIES AND READER TRAINING.
MedXViewer (Medical eXtensible Viewer) has been developed to address the need for workstation-independent, picture archiving and communication system (PACS)-less viewing and interaction with anonymised medical images. The aim of this paper is to describe the design and features of MedXViewer as well as to introduce the new features available in the latest release (version 1.2). MedXViewer currently supports digital mammography and tomosynthesis. The flexible software design used to develop MedXViewer allows it to be easily extended to support other imaging modalities. Regions of interest can be drawn by a user, and any associated information about a mark, an image or a study can be added. The questions and settings can be easily configured depending on the need of the research allowing both ROC and FROC studies to be performed. Complex tree-like questions can be asked where a given answer presents the user to new questions. The hanging protocol can be specified for each study. Panning, windowing, zooming and moving through slices are all available while modality-specific features can be easily enabled, e.g. quadrant zooming in digital mammography and tomosynthesis studies. MedXViewer can integrate with a web-based image database OPTIMAM Medical Image Database allowing results and images to be stored centrally. The software can, alternatively, run without a network connection where the images and results can be encrypted and stored locally on a machine or external drive. MedXViewer has been used for running remote paper-less observer studies and is capable of providing a training infrastructure and coordinating remote collaborative viewing sessions.


Effect of optimum therapeutic dose of poldine on acid secretion, gastric acidity, gastric emptying, and serum gastrin concentration after a protein meal.
An oral optimum therapeutic dose of poldine was established in 5 normal subjects. Acid secretion in response to a protein meal was measured for 3 hr by continuous intragastric titration with sodium bicarbonate. Poldine 30 min before the meal reduced food-stimulated acid secretion from zero to 60% in the 5 subjects (average inhibition 32%). Poldine inhibited histamine-stimulated acid secretion to approximately the same extent. In separate experiments, gastric acidity after the meal was allowed to seek its natural level (i.e., there was notitration with bicarbonate). Poldine reduced average hydrogen concentration of the gastric contents by 85 to 50% from 1.5 to 3 hr after the meal. Since poldine did not alter the volume or the buffer content of the stomach, poldine inhibition of gastric acidity is due entirely to reduction of acid secretion and not to delayed emptying of food buffer. Poldine had no consistent effect on serum gastrin concentration after the meal when pH was maintained at a constant level by titration with bicarbonate; therefore, poldine inhibition of acid secretion is not mediated by a reduction of serum gastrin concentration.


Communication tools and patient satisfaction: A scoping review.
This scoping review aimed to present an overview of the literature on communication tools in esthetic dentistry. A variety of communication tools have been proposed to include patients in the shared decision-making (SDM) workflow. Only little is known about implementing communication tools in dentistry and their impact on patient communication and patient satisfaction. A systematic literature search was performed in Medline, Embase, Cochrane, and World of Science to identify if communication tools have an impact on patient satisfaction. The search included studies from January 1, 2000 to March 3, 2020 published in English, focusing on patient communication tools and patient satisfaction in esthetic dentistry. Out of 6678 records, 53 full-texts were examined. Ten studies were included. Data of the included studies were extracted systematically and subsequently analyzed. All studies found that patient communication utilizing specific communication tools positively impacted either patient satisfaction, patient-dentist relationship, information retention, treatment acceptance, quality of care or treatment outcome. Additional communication tools besides conventional verbal communication are able to enhance patient satisfaction, improve quality of care and establish a better patient-dentist relationship. It seems essential to further develop standardized communication tools for SDM in dental medicine, which will allow the comparison of research on this topic. This scoping review shows the importance of patient involvement in the decision-making process for improved patient satisfaction with esthetic dental treatments. With an increased implementation of communication tools, patient satisfaction and SDM may further improve in the future.


Dichotomy of major bacterial phyla inferred from gene arrangement comparisons.
A computer search for gene arrangements that are present in Gram-positive bacteria but are absent from Proteobacteria and vice versa was carried out. Four such arrangements were detected, based on which major bacterial phyla were divided into two groups; Thermotoga, Deinococcus-Thermus, Chloroflexi (green non-sulfur bacteria), and Fusobacteria, represent Gram-positive bacterial gene arrangements, while Aquifex, Spirochetes, Planctomycetes, Chlorobi (green sulfur bacteria), Bacteroides show Proteobacterial arrangements. The division is almost consistent with another partition of the major phyla based on the comparison of domain architectures of RNA polymerase subunits and sigma factor, suggesting a fundamental split of the major bacterial phyla at an early stage of bacterial evolution.


Improvement of xylanase production in solid-state fermentation by alkali tolerant Aspergillus versicolor MKU3.
To optimize the media components for xylanase production by Aspergillus versicolor MKU3 in solid-state fermentation (SSF). Medium optimization was carried out using De Moe's fractional factorial design with seven components. Maximum production of xylanase 3249.9 U g(-1) was obtained in SSF with an optimized medium containing (g l(-1)): NaNO(3), 20; K(2)HPO(4), 20; MgSO(4), 10; FeSO(4), 0.001; KCl, 1; peptone, 10 and yeast extract, 10. Four components namely NaNO(3), MgSO(4), peptone and K(2)HPO(4) significantly increased the xylanase production by A. versicolor MKU3. Fractional factorial design was used to optimize the seven components in the fermentation medium for SSF. The optimized media increased xylanase production by 3.4-fold. Aspergillus versicolor MKU3 produced maximum xylanase after two steps of media optimization under alkaline condition. This medium will be significant value for xylanase production in SSF.


Intestinal iron absorption and mucosal transferrin in rats subjected to hypoxia.
Three days hypoxia (0.5 atm) increased the haemoglobin and haematocrit values in rats paralleled by enhanced intestinal iron absorption. The destination of recently-absorbed iron was primarily the erythropoietic system, viz. bone marrow, spleen and red cells. Total plasma transferrin, was increased by 30%, but no significant changes in mucosal transferrin were found. No increase in labelling of mucosal transferrin by absorbed iron was observed. These results suggest that mucosal transferrin does not play a major role in the regulation of intestinal iron absorption in hypoxia.


Variation in pediatric and adolescent electronic health data sharing practices under the 21st Century Cures Act.
To describe real-world practices and variation in implementation of the Information Blocking provisions amongst healthcare organizations caring for pediatric patients. An online survey regarding implementation practices was distributed to representatives from 10 participating US healthcare organizations located in 6 different states. The survey was followed by structured interviews conducted through video conference. Information was gathered about implementation practices at each organization, with a focus on patient and proxy portal access to, and segmentation capabilities of, certain data classes listed in the United States Core Data for Interoperability Version 1. All organizations had implemented the information blocking provisions at their institution. All organizations utilized different portal account types for proxies and users. All organizations reported the capability of sharing labs, medications, problem lists, imaging, and notes with the parent/guardian of the non-adolescent minor user with differences in how sensitive elements within the data classes were protected. Variability existed in how data was shared with the remaining user types. Significant variability exists in how organizations have implemented the information blocking rules. Variation in data sharing and data access between institutions can result in privacy breaches and create confusion about completeness of data for patients and families. Healthcare organizations have utilized varying strategies to comply with the information blocking provisions of the 21st Century Cures Act. Increased clarity from the Office of the National Coordinator for Health Information Technology on minor, adolescent, and caregiver privacy and improved segmentation capabilities from Electronic Health Record vendors is needed.


Senataxin and R-loops homeostasis: multifaced implications in carcinogenesis.
R-loops are inherent byproducts of transcription consisting of an RNA:DNA hybrid and a displaced single-stranded DNA. These structures are of key importance in controlling numerous physiological processes and their homeostasis is tightly controlled by the activities of several enzymes deputed to process R-loops and prevent their unproper accumulation. Senataxin (SETX) is an RNA/DNA helicase which catalyzes the unwinding of RNA:DNA hybrid portion of the R-loops, promoting thus their resolution. The key importance of SETX in R-loops homeostasis and its relevance with pathophysiological events is highlighted by the evidence that gain or loss of function SETX mutations underlie the pathogenesis of two distinct neurological disorders. Here, we aim to describe the potential impact of SETX on tumor onset and progression, trying to emphasize how dysregulation of this enzyme observed in human tumors might impact tumorigenesis. To this aim, we will describe the functional relevance of SETX in regulating gene expression, genome integrity, and inflammation response and discuss how cancer-associated SETX mutations might affect these pathways, contributing thus to tumor development.


Development of self-assembled zein-fucoidan complex nanoparticles as a delivery system for resveratrol.
Resveratrol is a well-studied dietary polyphenol with diverse health-promoting bioactivities. However, the aqueous insolubility and chemical instability of resveratrol hamper its practical application. This study set out to address these limitations by constructing zein-fucoidan composite nanoparticles as a delivery system of resveratrol. The optimized resveratrol-loaded zein-fucoidan particles (RE-ZFP) were obtained at zein-to-fucoidan ratio of 2:1 (w/w) and zein-to-resveratrol ratio of 10:1 (w/w), and RE-ZFP showed evenly distributed and smoothly spherical microstructures, mean particle size of 121 nm, ζ-potential of - 41 mV, encapsulation efficiency for resveratrol of 95.4%. Electrostatic, steric, hydrophobic, and hydrogen-bonding interactions were major forces required to form RE-ZFP. In addition, RE-ZFP exhibited greater photostability and colloidal stability (including pH, ionic, and storage stabilities) than resveratrol-loaded zein particles (RE-ZP). Particularly, RE-ZFP showed fairly good pH stability. Moreover, zein-fucoidan-based delivery system exhibited a controlled release of resveratrol under in vitro digestion. Finally, zein-fucoidan nanocarriers presented extremely low cytotoxicity to HIEC-6 cells. All the findings demonstrate that the zein-fucoidan nanoparticles developed in the current work will be a prospective strategy for loading resveratrol and other hydrophobic bioactive ingredients and thus extending their application in nutraceuticals or pharmaceuticals.


Measuring E(GSH) and H2O2 with roGFP2-based redox probes.
Redox biochemistry plays an important role in a wide range of cellular events. However, investigation of cellular redox processes is complicated by the large number of cellular redox couples, which are often not in equilibrium with one another and can vary significantly between subcellular compartments and cell types. Further, it is becoming increasingly clear that different redox systems convey different biological information; thus it makes little sense to talk of an overall "cellular redox state". To gain a more differentiated understanding of cellular redox biology, quantitative, redox couple-specific, in vivo measurements are necessary. Unfortunately our ability to investigate specific redox couples or redox-reactive molecules with the necessary degree of spatiotemporal resolution is very limited. The development of genetically encoded redox biosensors offers a promising new way to investigate redox biology. Recently developed redox-sensitive green fluorescent proteins (roGFPs), genetically fused to redox-active proteins, allow rapid equilibration of the roGFP moiety with a specific redox couple. Two probes based on this principle are now available: Grx1-roGFP2 for the measurement of glutathione redox potential (E(GSH)) and roGFP2-Orp1 for measuring changes in H(2)O(2) concentration. Here we provide a detailed protocol for the use of these probes in both yeast and mammalian systems using either plate-reader- or microscopy-based measurements.


A Comparison of Surgical Outcomes of Carbon Dioxide Laser Versus Conventional Cold Instrument Excision of Benign Vocal Cord Lesions.
Benign vocal fold lesions affect the vibratory function of the vocal folds and cause dysphonia. Surgical excision has been the mainstay of management of benign vocal fold lesions for decades. This study compares the surgical outcomes of cold instruments versus carbon dioxide (CO2) laser excision of benign vocal fold lesions. A total of 49 cases diagnosed with benign vocal fold lesions were divided randomly to undergo excision either by conventional cold steel method or by CO2 laser. The postoperative assessment of the groups was done by videostroboscopy, acoustic analysis and voice handicap index. There was a significant improvement (P value < 0.05) when preoperative values of the parameters were compared with postoperative values in the individual groups. However, there was no significant difference when the two groups were compared with each other in terms of outcomes. Both the surgical techniques provide good outcomes in management of benign vocal fold lesions and each has its own advantages and disadvantages.


Epithelial-to-mesenchymal transition status correlated with ultrastructural features, and TP53 mutation in patient-derived oral cancer cell lines.
Oral Squamous Cell Carcinoma (OSCC) is a highly prevalent cancer in the Indian subcontinent. The major cause of mortality in OSCC patients is metastasis. Epithelial-to-mesenchymal transition (EMT) marks an important step in the metastatic process. Additionally, TP53, an important tumor suppressor gene, is also a significant determinant of the treatment outcome, and also plays a role in EMT. Therefore, understanding the interconnections between ultrastructural features, EMT status and TP53 mutational status is of vital importance. The ultrastructure of five OSCC cell lines was visualized by transmission electron microscopy. Trans-well invasion and migration assays as well as scratch-wound assay, and the expression of various EMT-related genes were utilized to assess the EMT status of the cell lines. The TP53 exons were amplified for the ACOSC3, ACOSC4 and ACOSC16 cell lines and sequenced and the mutations in the gene were identified by sequence alignment. The TP53 mutation in the UPCI:SCC029B cell line has been previously reported, while UPCI:SCC040 has been reported to harbor a wild type TP53. The ACOSC4 cell line which showed the shortest intercellular gaps, also had the least invasive and migratory potential. Interestingly, ACOSC4 showed the highest expression of E-cadherin and the lowest expression of Vimentin, TWIST1, ZEB1, and MMPs. Additionally, TP53 gene of ACOSC4 was unmutated, whereas the ACOSC3 and ACOSC16 harbored TP53 mutations. The mutation in ACOSC3 (R196*) was also found in 7 TCGA samples. Similarly, the UPCI:SCC040 cell line that harbors a wild type TP53 showed shorter intracellular gaps. Cellular migratory properties are associated with cellular ultrastructure, epithelial-to-mesenchymal transition status and the status of TP53 mutation in the genome.


Evaluation of piggyBac-mediated anti-CD19 CAR-T cells after ex vivo expansion with aAPCs or magnetic beads.
Adoptive immunotherapy is a new potential method of tumour therapy, among which anti-CD19 chimeric antigen receptor T-cell therapy (CAR-T cell), is a typical treatment agent for haematological malignancies. Previous clinical trials showed that the quality and phenotype of CAR-T cells expanded ex vivo would seriously affect the tumour treatment efficacy. Although magnetic beads are currently widely used to expand CAR-T cells, the optimal expansion steps and methods have not been completely established. In this study, the differences between CAR-T cells expanded with anti-CD3/CD28 mAb-coated beads and those expanded with cell-based aAPCs expressing CD19/CD64/CD86/CD137L/mIL-15 counter-receptors were compared. The results showed that the number of CD19-specific CAR-T cells with a 4-1BB and CD28 co-stimulatory domain was much greater with stimulation by aAPCs than that with beads. In addition, the expression of memory marker CD45RO was higher, whereas expression of exhausted molecules was lower in CAR-T cells expanded with aAPCs comparing with the beads. Both CAR-T cells showed significant targeted tumoricidal effects. The CAR-T cells stimulated with aAPCs secreted apoptosis-related cytokines. Moreover, they also possessed marked anti-tumour effect on NAMALWA xenograft mouse model. The present findings provided evidence on the safety and advantage of two expansion methods for CAR-T cells genetically modified by piggyBac transposon system.


Skeletal growth after muscular reconstruction for cleft lip, alveolus and palate.
To compare two treatments for unilateral cleft lip and palate. Follow-up study. University department, Germany. 110 children with unilateral cleft lip and palate, 50 of whom were treated between 1980 and 1988 (group 1) and 60 of whom were treated between 1970 and 1979 (group 2). Group 1 had no dentofacial treatment before operation. At the age of 3 months they had musculoperiosteal reconstruction with no orthopaedic treatment postoperatively. At the age of 9-12 months they had the velar muscle reconstructed but no orthopaedic treatment to follow. Group 2 had dentofacial treatment before operation. At the age of 6 months they had their lips operated on by Millard's technique. Postoperatively they had dentofacial orthopaedic treatment followed, at the age of 2.5 years, by palatal surgery by the Campbell-Widmaier technique. This was followed by more dentofacial orthopaedic treatment. Main outcome measure--Growth of the midface skeleton. The course of the anterior tooth segment was similar in the two groups, as was the transverse development of the maxilla. Analyses of both dental casts and lateral cephalometric radiographs showed that the skeletal development in group 1 (who had undergone reconstruction of the perioral and perinasal muscles) was better than in group 2 (who had not) despite the fact that group 1 had had no orthopaedic growth stimulation. If the primary and secondary growth centres are not joined at the first operation and the midfacial muscles are not reconstructed, even orthopaedic growth stimulation will not compensate for the defect.


Structure elucidation of four possible biogenic organohalogens using isotope exchange mass spectrometry.
The molecular structures of four unknown bioaccumulating halogenated compounds, C10H6N2Br3Cl3, C10H6N2Br4Cl2, C10H6N2Br5Cl, and C10H6N2Br6 were characterized using isotope exchange positive chemical ionization (IE-PCI) mass spectrometry (MS) and identified by comparison to synthesized standards. NH3 and ND3 were used as reagent gases for the IE-PCI-MS experiment. The shift in mass of the quasimolecular ion between the NH3 and ND3 PCI obtained spectra indicated the number of exchangeable hydrogens attached to the two nitrogen atoms in C10H6N2Br4Cl2, and thus the type of amines present (primary, secondary, or tertiary). 19 compounds (13 amines of varying degree of substitution; six containing no nitrogen) were used as reference compounds and controls in the experiment to validate the IE-PCI technique. The results of the IE-PCI-MS indicated the presence of two tertiary amine functional groups. The molecular structures of the four hexahalogenated compounds were then proposed to be 1,1'-dimethyl-3,3',4,-tribromo-4',5,5'-trichloro-2,2'-bipyrrole, 1,1'-dimethyl-3,3',4,4'-tetrabromo-5,5'-dichloro-2,2'-bipyrrole, 1,1'-dimethyl-3,3',4,4',5-pentabromo-5'-chloro-2,2'-bipyrrole, and 1,1'-dimethyl-3,3',4,4',5,5'-hexabromo-2,2'-bipyrrole and subsequently synthesized. Comparison of retention times and electron capture negative ionization (ECNI) full scans on various gas chromatography (GC) columns between the synthesized bipyrroles and the corresponding unknown compounds in biota indicated that three of the unknown compounds--possible marine natural products--were the proposed halogenated dimethyl bipyrroles. The placement of the halogen atoms on the fourth compound, C10H6N2Br3Cl3 could not be unequivocally determined since the synthesized standard could not be fully characterized.


Assessing the miRNA sponge potential of RUNX1T1 in t(8;21) acute myeloid leukemia.
t(8;21) acute myeloid leukemia (AML) is characterized by a translocation between chromosomes 8 and 21 and formation of a distinctive RUNX1-RUNX1T1 fusion transcript. This translocation places RUNX1T1 under control of the RUNX1 promoter leading to a pronounced upregulation of RUNX1T1 transcripts in t(8;21) AML, compared to normal hematopoietic cells. We investigated the role of highly-upregulated RUNX1T1 under the hypothesis that it acts as competing endogenous RNA (ceRNA) titrating microRNAs (miRNAs) away from their target transcripts and thus contributes to AML formation. Using publicly available t(8;21) AML RNA-Seq and miRNA-Seq data available from The Cancer Genome Atlas (TCGA) project, we obtained a network consisting of 605 genes that may act as ceRNAs competing for miRNAs with the suggested RUNX1T1 miRNA sponge. Among the 605 ceRNA candidates, 121 have previously been implied in cancer development. Players in the integrin, cadherin, and Wnt signaling pathways affected by the RUNX1T1 sponge were overrepresented. Finally, among a set of 21 high interest RUNX1T1 ceRNAs we found multiple genes that have previously been linked to AML formation. In conclusion, our study offers a novel look at the role of the RUNX1-RUNX1T1 fusion transcript in t(8;21) AML beyond previously investigated genetic and epigenetic aberrations.


Tissue factor pathway inhibitor production by human proximal tubular epithelial cells in culture.
Fibrin deposition in the peritubular capillaries and along the tubular basement membrane is commonly observed in several renal diseases and suggests the involvement of blood coagulation in tubulointerstitial damage. It has been demonstrated that tissue factor (TF) is present in tubular epithelial cells of animal models of nephritis. Tissue factor pathway inhibitor (TFPI) regulates the extrinsic pathway of blood coagulation through its ability to inhibit TF activity and it is now thought to be produced mainly by the vascular endothelial cells. We examined whether human proximal tubular epithelial cells (PTEC) could produce TFPI and attempted to clarify the regulatory factors affecting TFPI production. Cultured human PTEC were used. The procoagulant activity (PCA) in PTEC lysate was quantified by measurement of the one-stage recalcification time. TFPI in the cell supernatants was measured by ELISA. The mRNA of TF and TFPI in PTEC was analyzed by reverse transcriptase polymerase chain reaction (RT-PCR). PCA which is compatible with TF activity was present in the PTEC lysate. TF mRNA and TFPI mRNA were detected in PTEC. The amount of TFPI increased over time in the cell supernatants. Immnoblot analysis revealed 40 kD protein of TFPI, and TFPI antigen was demonstrated in PTEC by immunofluorescence. The concentration of TFPI was significantly increased following incubation with thrombin and heparin in a dose- and time-dependent manner, although the amount of TFPI mRNA was not changed. Our study showed that TFPI is produced in cultured PTEC and added one more cell type that produced TFPI other than endothelial cells. Thrombin and heparin stimulated TFPI secretion from PTEC. TFPI of PTEC may act against generation of thrombin and tubular fibrin formation induced by tissue factor activation. The augmentation of TFPI secretion by heparin may play an important role in the modulation of anticoagulant properties of PTEC.


GATA3 recruits UTX for gene transcriptional activation to suppress metastasis of breast cancer.
GATA3 has emerged as a prominent transcription factor required for maintaining mammary-gland homeostasis. GATA3 loss is associated with aggressive breast cancer development, but the mechanism by which breast cancer is affected by the loss of GATA3 function remains unclear. Here, we report that GATA3 expression is positively correlated with the expression of UTX, a histone H3K27 demethylase contained in the MLL4 methyltransferase complex, and that GATA3 recruits the chromatin-remodeling MLL4 complex and interacts directly with UTX, ASH2L, and RBBP5. Using RNA sequencing and chromatin immunoprecipitation and sequencing, we demonstrate that the GATA3/UTX complex synergistically regulates a cohort of genes including Dicer and UTX, which are critically involved in the epithelial-to-mesenchymal transition (EMT). Our results further show that the GATA3-UTX-Dicer axis inhibits EMT, invasion, and metastasis of breast cancer cells in vitro and the dissemination of breast cancer in vivo. Our study implicates the GATA3-UTX-Dicer axis in breast cancer metastasis and provides new mechanistic insights into the pathophysiological function of GATA3.


Successful lichen translocation on disturbed gypsum areas: A test with adhesives to promote the recovery of biological soil crusts.
The loss of biological soil crusts represents a challenge for the restoration of disturbed environments, specifically in particular substrates hosting unique lichen communities. However, the recovery of lichen species affected by mining is rarely addressed in restoration projects. Here, we evaluate the translocation of Diploschistes diacapsis, a representative species of gypsum lichen communities affected by quarrying. We tested how a selection of adhesives could improve thallus attachment to the substrate and affect lichen vitality (as CO2 exchange and fluorescence) in rainfall-simulation and field experiments. Treatments included: white glue, water, hydroseeding stabiliser, gum arabic, synthetic resin, and a control with no adhesive. Attachment differed only in the field, where white glue and water performed best. Adhesives altered CO2 exchange and fluorescence yield. Notably, wet spoils allowed thalli to bind to the substrate after drying, revealing as the most suitable option for translocation. The satisfactory results applying water on gypsum spoils are encouraging to test this methodology with other lichen species. Implementing these measures in restoration projects would be relatively easy and cost-effective. It would help not only to recover lichen species in the disturbed areas but also to take advantage of an extremely valuable biological material that otherwise would be lost.


An SVM method using evolutionary information for the identification of allergenic proteins.
This study presents an allergenic protein prediction system that appears to be capable of producing high sensitivity and specificity. The proposed system is based on support vector machine (SVM) using evolutionary information in the form of an amino acid position specific scoring matrix (PSSM). The performance of this system is assessed by a 10-fold cross-validation experiment using a dataset consisting of 693 allergens and 1041 non-allergens obtained from Swiss-Prot and Structural Database of Allergenic Proteins (SDAP). The PSSM method produced an accuracy of 90.1% in comparison to the methods based on SVM using amino acid, dipeptide composition, pseudo (5-tier) amino acid composition that achieved an accuracy of 86.3, 86.5 and 82.1% respectively. The results show that evolutionary information can be useful to build more effective and efficient allergen prediction systems.


The clinical significance of internal mammary lymph node (IMLN) biopsy during autologous reconstruction in breast cancer patients.
The clinical significance of IMLN metastases in breast cancer is controversial. Although IMLN status is an integral part of current AJCC staging of breast cancer, the elective sampling of IMLN is not part of routine surgery for breast cancer. The purpose of this study was to determine the incidence of IMLN metastases, associated risk factors if any, and its impact on further management and outcome. We retrospectively studied 470 cases that underwent autologous reconstruction surgery between 2002 and 2014. Of 470 cases, 157 breast cancer cases had histology-confirmed IMLN removal during the reconstruction. Only 9 patients (6 %) showed IMLN metastases as compared to 45 (34 %) that showed axillary nodal metastases (p < 0.01). Interestingly, 4 patients had metastases limited to IMLN without any metastases to axillary nodes. IMLN metastasis was significantly associated with age <40 years, lymphovascular invasion, and negative PR status. IMLN metastasis resulted in upstaging of 2 patients from stage I to III, and 1 from stage II to III. Five patients received additional chest wall radiation to target the positive IMLNs. Nine of 157 (6 %) patients with IMLN removal during reconstruction had loco-regional recurrence/metastasis as compared to 20 of 293 (7 %) patients without IMLN removal (p > 0.05) (follow-up, 1-134 months). The overall rate of IMLN metastases (6 %) is much lower than the rate of axillary node metastases. Selective biopsy of IMLNs in patients with breast cancer, especially if younger than 40 years, and with lymphovascular invasion and negative PR status, may guide adjuvant treatment.


Codon bias and noncoding GC content correlate negatively with recombination rate on the Drosophila X chromosome.
The patterns and processes of molecular evolution may differ between the X chromosome and the autosomes in Drosophila melanogaster. This may in part be due to differences in the effective population size between the two chromosome sets and in part to the hemizygosity of the X chromosome in Drosophila males. These and other factors may lead to differences both in the gene complements of the X and the autosomes and in the properties of the genes residing on those chromosomes. Here we show that codon bias and recombination rate are correlated strongly and negatively on the X chromosome, and that this correlation cannot be explained by indirect relationships with other known determinants of codon bias. This is in dramatic contrast to the weak positive correlation found on the autosomes. We explored possible explanations for these patterns, which required a comprehensive analysis of the relationships among multiple genetic properties such as protein length and expression level. This analysis highlights conserved features of coding sequence evolution on the X and the autosomes and illuminates interesting differences between these two chromosome sets.


The impact of neighborhood social disadvantage on abdominal aortic aneurysm severity and management.
Recent studies have highlighted socioeconomic disparities in the severity and management of abdominal aortic aneurysm (AAA) disease. However, these studies focus on individual measures of social disadvantage such as income and insurance status. The area deprivation index (ADI), a validated measure of neighborhood deprivation, provides a more comprehensive assessment of social disadvantage. Therefore, we examined the impact of ADI on AAA severity and its management. We identified all patients who underwent endovascular or open repair of an AAA in the Vascular Quality Initiative registry between 2003 and 2020. An ADI score of 1 to 100 was assigned to each patient based on their residential zip code, with higher ADI scores corresponding with increasing deprivation. Patients were categorized by ADI quintiles. Outcomes of interest included rates of ruptured AAA (rAAA) repair versus an intact AAA repair and rates of endovascular repair (EVAR) versus the open approach. Logistic regression was used to evaluate for an independent association between ADI quintile and these outcomes. Among 55,931 patients who underwent AAA repair, 6649 (12%) were in the lowest ADI quintile, 11,692 (21%) in the second, 15,958 (29%) in the third, 15,035 (27%) in the fourth, and 6597 (12%) in the highest ADI quintile. Patients in the two highest ADI quintiles had a higher proportion of rAAA repair (vs intact repair) compared with those in the lowest ADI quintile (8.8% and 9.1% vs 6.2%; P < .001). They were also less likely to undergo EVAR (vs open approach) when compared with the lowest ADI quintile (81% and 81% vs 88%; P < .001). There was an overall trend toward increasing rAAA and decreasing EVAR rates with increasing ADI quintiles (P < .001). In adjusted analyses, when compared with patients in the lowest ADI quintile, patients in the highest ADI quintile had higher odds of rAAA repair (odds ratio, 1.4; 95% confidence interval, 1.2-1.8; P < .001) and lower odds of undergoing EVAR (odds ratio, 0.54; 95% confidence interval, 0.45-0.65; P < .001). Among patients who underwent AAA repair in the Vascular Quality Initiative, those with higher neighborhood deprivation had significantly higher rates of rAAA repair (vs intact repair) and lower rates of EVAR (vs open approach). Further work is needed to better understand neighborhood factors that are contributing to these disparities to identify community-level targets for improvement.


Two N-methyl-D-aspartate receptors in rat dorsal root ganglia with different subunit composition and localization.
N-methyl-D-aspartate (NMDA) receptors in sensory afferents participate in chronic pain by mediating peripheral and central sensitization. We studied the presence of NMDA receptor subunits in different types of primary afferents. Western blots indicated that rat dorsal root ganglia (DRG) contain NR1, NR2B, NR2C, and NR2D but not NR2A. Real-time RT-PCR showed that NR2B and NR2D were expressed at higher levels than NR2A and NR2C in DRG. Immunofluorescence with an antibody that recognized NR1 and another that recognized NR2A and NR2B showed that NR1 and NR2B colocalized in 90% of DRG neurons, including most A-fibers (identified by the presence of neurofilament 200 kDa). In contrast, an antibody recognizing NR2C and NR2D labeled only neurofilament-negative DRG profiles. This antibody stained practically all DRG cells that contained calcitonin gene-related peptide and neurokinins and those that bound isolectin B4. The percentage of cells immunoreactive for NR1, NR2A/NR2B, and NR2C/NR2D were the same in the T9, T12, L4, and L6 DRG. The intracellular distribution of the NR2 subunits was strikingly different: Whereas NR2A/NR2B immunoreactivity was found in the Golgi apparatus and occasionally at the plasma membrane, NR2C/NR2D immunoreactivity was found in the cytoplasm but not in the Golgi. The NR1 subunit was present throughout the cytoplasm and was more intense in the Golgi. These findings indicate that DRG neurons have two different NMDA receptors, one containing the NR1, NR2D, and possibly the NR2C subunits, found only in C-fibers, and the diheteromer NR1/NR2B, present in the Golgi apparatus of both A- and C-fibers.


Spectral signatures of mirror movements in the sensori-motor connectivity in kallmann syndrome.
Mirror movements (MM) might be observed in congenital and acquired neurodegenerative conditions but their anatomic-functional underpinnings are still largely elusive. This study investigated the spectral changes of resting-state functional connectivity in Kallmann Syndrome (hypogonadotropic hypogonadism with hypo/anosmia with or without congenital MM) searching for insights into the phenomenon of MM. Forty-four Kallmann syndrome patients (21 with MM) and 24 healthy control subjects underwent task (finger tapping) and resting-state functional MRI. The spatial pattern of task-related activations was used to mask regions and select putative motor networks in a spatially independent component analysis of resting-state signals. For each resting-state independent component time-course power spectrum, we extracted the relative contribution of four separate bands: slow-5 (0.01-0.027 Hz), slow-4 (0.027-0.073 Hz), slow-3 (0.073-0.198 Hz), slow-2 (0.198-0.25 Hz), and analyzed the variance between groups. For the sensorimotor network, the analysis revealed a significant group by frequency interaction (P = 0.002) pointing to a frequency shift in the spectral content among subgroups with lower slow-5 band and higher slow-3 band contribution in Kallmann patients with MM versus controls (P = 0.028) and with lower slow-5 band contribution between patients with and without MM (P = 0.057). In specific regions, as obtained from hand motor activation task analysis, spectral analyses demonstrated a lower slow-5 band contribution in Kallmann patients with MM versus both controls and patients without MM (P < 0.05). In Kallmann syndrome, the peculiar phenomenon of bimanual synkinesis is associated at rest with regionally and spectrally selective functional connectivity changes pointing to a distinctive cortical and subcortical functional reorganization. Hum Brain Mapp 39:42-53, 2018. © 2017 Wiley Periodicals, Inc.


Single-atom cobalt array bound to distorted 1T MoS2 with ensemble effect for hydrogen evolution catalysis.
The grand challenge in the development of atomically dispersed metallic catalysts is their low metal-atom loading density, uncontrollable localization and ambiguous interactions with supports, posing difficulty in maximizing their catalytic performance. Here, we achieve an interface catalyst consisting of atomic cobalt array covalently bound to distorted 1T MoS2 nanosheets (SA Co-D 1T MoS2). The phase of MoS2 transforming from 2H to D-1T, induced by strain from lattice mismatch and formation of Co-S covalent bond between Co and MoS2 during the assembly, is found to be essential to form the highly active single-atom array catalyst. SA Co-D 1T MoS2 achieves Pt-like activity toward HER and high long-term stability. Active-site blocking experiment together with density functional theory (DFT) calculations reveal that the superior catalytic behaviour is associated with an ensemble effect via the synergy of Co adatom and S of the D-1T MoS2 support by tuning hydrogen binding mode at the interface.


Acetabular reinforcement in total hip replacement.
In conclusion, based on our experimental and clinical material and analysis of failures, we recommend wire mesh reinforcement and bone graft for patients with mild to moderate protrusio. If the floor is strong but the pillars deficient, then the Eichler ring alone is the best implant. The combined system of wire mesh and Eichler ring should be used in cases of protrusion with a large deficiency of the acetabular floor and for protrusio with pillar weakness. Furthermore a bone graft should be used to reinforce the acetabular floor in addition to any prosthetic device.


Nailing of proximal ulna fractures: biomechanical comparison of a new locked nail with angular stable plating.
Proximal ulna fractures are common injuries and frequently treated with angular stable plating. This surgical option shows good functional results. Relevant drawbacks such as large soft tissue exposure, compromised blood supply of fracture fragments and disturbing osteosynthetic material are described. The aim of this study was to compare a new locked proximal ulna nail with angular stable plating in a biomechanical testing setup for extraarticular proximal ulna fractures. Ten pairs of sawbones with a Jupiter type IIB proximal ulna fracture (OTA 2U1A3.1) were tested after osteosynthesis with the mentioned implants in a servo-pneumatic testing machine. The testing setup simulates physiological joint motion (0°-90°) under cyclic loading (30-300 N). Primary stability and loosening of both constructs were quantified using micromotion video-analysis after 608 test cycles. The micromotion analysis showed significantly higher primary stability of the locked nail (0.29 ± 0.13 mm) compared to the angular stable plate (0.97 ± 0.30 mm, p < 0.001). Both implants showed a low amount of loosening after completion of the test cycles. The construct with the locked nail (0.08 ± 0.06 mm) showed significantly lower dislocation of the fragments measured at the anterior cortex (plate 0.24 ± 0.13 mm, p < 0.001). Nailing of proximal ulna fractures shows significantly higher primary stability and lower loosening compared to angular stable plating in our testing setup.


Superior Cerebellar Arteries Originating from the Posterior Cerebral Arteries but Normal Course of the Oculomotor Nerves.
The posterior cerebral artery (PCA) is a branch of the terminal part of the basilar artery and perfuses the temporal lobes, midbrain, thalamus, and the posterior inferior portion of the parietal lobes. It is divided into P1-P4 segments. Variations in the P1 segment of the PCA are important to neurosurgeons when performing surgery, for example, on basilar tip aneurysms. We report bilateral superior cerebellar artery (SCA) arising from the P1 segment of the PCA. Such a configuration appears to be uncommon but should be kept in mind by neurosurgeons, neurointerventionalists, and neuroradiologists.


In vitro and in vivo anti-inflammatory potential of Cryptolepis buchanani.
Cryptolepis buchanani Roem. & Schult. (Asclepiadaceae), a climbing tree, is used as folk medicine in southeast Asia. In Thailand, the stem of this plant is traditionally used for the treatment of inflammation, including arthritis, and muscle and joint pain. In the current study, the potential anti-inflammatory activity of a 50% ethanol extract of this plant was evaluated in a number of experimental models. For anti-acute inflammatory activity, results showed that the extract caused reduction of carrageenan-induced rat paw edema in addition to significant reduction of eicosanoid production from calcium ionophore A23187-stimulated rat peritoneal leukocytes. In a test for anti-chronic inflammatory potential utilizing the cotton thread-induced granuloma, the extract caused significant lowering of granulation tissue formation. The reduction of tumor necrosis factor-alpha (TNF-alpha) release from LPS-stimulated human monocytic cell line (THP-1) was also demonstrated in cells that were pre-incubated with the extract. An additional important feature of Cryptolepis buchanani is its low toxicity, especially by oral treatment, which significantly encourages clinical trials of this extract in the human. In conclusion, the results give scientific support to the traditional use of this plant for combating inflammation. Further investigations are required to identify the active constituents responsible for the anti-inflammatory activity of Cryptolepis buchanani. Subacute and chronic toxicological studies in animals are also needed before clinical trials.


The antiproliferative effects of biologically active isomers of conjugated linoleic acid on human colorectal and prostatic cancer cells.
The antiproliferative effects of two commercial preparations of conjugated linoleic acid (CLA) and their constituent isomers, cis-9, trans-11 (c9,t11)-CLA, c9,c11-CLA, and t10,c12-CLA, were determined in vitro using human colorectal (HT-29, MIP-101) and prostate (PC-3) carcinoma cells adapted to serum-free medium. The antiproliferative effects of the preparations were dependent upon the type and concentration of CLA isomer present. The t10,c12-CLA isomer exhibited the greatest potency against colorectal cancer proliferation, and the c9,t11 and t10,c12 isomers were moderately effective against prostate cancer. The t10,c12 isomer induced caspase-dependent apoptosis in MIP-101 and PC-3 cells. The results are the first to demonstrate that physiologic levels of two CLA preparations, their constituent isomers, and the c9,t11-CLA elongation product, c11,t13-conjugated eicosadienoic acid, induce dose-dependent inhibitory effects on cancer proliferation in vitro. Novel CLA preparations may prove effective as chemopreventive supplements for individuals at risk of or diagnosed with colorectal or prostate cancer.


High altitude exposure affects male reproductive parameters: could it also affect the prostate?†.
Living at high altitudes and living with prostatic illness are two different conditions closely related to a hypoxic environment. People at high altitudes exposed to acute, chronic or intermittent hypobaric hypoxia turn on several mechanisms at the system, cellular, and molecular level to cope with oxygen atmosphere scarcity maintaining the oxygen homeostasis. This exposure affects the whole organism and function of many systems, such as cardiovascular, respiratory, and reproductive. On the other hand, malignant prostate is related to the scarcity of oxygen in the tissue microenvironment due to its low availability and high consumption due to the swift cell proliferation rates. Based on the literature, this similarity in the oxygen scarcity suggests that hypobaric hypoxia, and other common factors between these two conditions, could be involved in the aggravation of the pathological prostatic status. However, there is still a lack of evidence in the association of this disease in males at high altitudes. This review aims to examine the possible mechanisms that hypobaric hypoxia might negatively add to the pathological prostate function in males who live and work at high altitudes. More profound investigations of hypobaric hypoxia's direct action on the prostate could help understand this exposure's effect and prevent worse prostate illness impact in males at high altitudes.


Deficit in a neural correlate of reality monitoring in schizophrenia patients.
Patients who suffer from the devastating psychiatric illness schizophrenia are plagued by hallucinations, bizarre behavior, and delusional ideas, such as believing that they are controlled by malevolent outside forces. A fundamental human cognitive operation that may contribute to these hallmark symptoms is the ability to maintain accurate and coherent self-referential processing over time, such as occurs during reality monitoring (distinguishing self-generated from externally perceived information). However, the neural bases for a disturbance in this operation in schizophrenia have not been fully explored. Using functional magnetic resonance imaging, we asked clinically stable schizophrenia patients to remember whether or not they had generated a target word during an earlier sentence completion task. We found that, during accurate performance of this self-referential source memory task, the schizophrenia subjects manifest a deficit in rostral medial prefrontal cortex (mPFC) activity--a brain region critically implicated in both the instantiation and the retrieval of self-referential information in healthy subjects. Impairment in rostral mPFC function likely plays a key role in the profound subjective disturbances that characterize schizophrenia and that are the aspect of the disorder most troubling to patients and to society at large.


Plasma C1q/TNF-related protein 9: a promising biomarker for diabetic renal vascular injury.
Adipocytokines are associated with the pathophysiology of type 2 diabetes (T2DM). We analyzed the relationship between levels of the plasma C1q/tumor necrosis factor-related protein 9 (CTRP9) and other adipocytokines or the endothelial function in patients with T2DM, and analyzed their trending manner. CTRP9 was detected in plasma from 14 out of a total of 28 patients. The values were not normally distributed. In comparing between groups in which CTRP9 was or was not detected, there were statistically significant differences in the high molecular weight adiponectin (HAN) and the urinary albumin/creatinine ratio (ACR). This indicates that both CTRP9 and HAN reflect the pathophysiology of renal involvement in T2DM. HAN correlated with Body Mass Index, ACR, and homeostasis model assessment of insulin resistance. However, CTRP9 did not correlate with HAN or any other parameters. CTRP9 independently trends in a different manner from HAN, and may reflect diabetic renal vascular risk in association with atherosclerosis and abnormal glucose metabolism besides of impaired vaso-relaxation in patients with T2DM.


[Effect of virulent and anttenuated variants of viruses of American equine encephalomyelitis on the mitotic activity of the cells].
A comparative study of reproduction of Venezuelan and Eastern equine encephalomyelitis (VEE and EEE) viruses in L cell culture showed the disorders of the mitotic activity of the infected cultures to depend on the variant of the inoculated virus and the degree of its attenuation. The highest number of pathological mitosis was observed within 12--24 hours after inoculation of the cultures, the attenuated variants of both the viruses causing lower numbers of pathological mitoses than virulent variants. EEE virus was found to induce accumulation of pyknotized nuclei in the stage of telophase in the culture.


Geographical patterns of persistence in duck guilds.
Geographical gradients of persistence in community structure have been suggested to be causally related to underlying gradients of species diversity, environmental variability and/or productivity. In order to test whether the persistence of breeding duck communities was dependent on any one of these three factors, thirty-three years of census data from the Canadian prairie and boreal forest regions was examined along geographical gradients of wetland habitat variability and productivity. For breeding ducks, locally derived patterns of persistence were generally independent of local habitat conditions. Persistence appeared to be related more to patterns of emigration and immigration in response to climatic conditions (i.e., drought) in the southern prairies than to local species richness, wetland habitat variability or productivity. It is suggested, therefore, that analyses of community persistence derived at small spatial scales may be of limited value if the structure of communities is not regulated by local conditions.


Neuroendocrine correlates of stress and tonic immobility.
Threatening stimuli challenging animal homeostasis are the primary events triggering defensive responses, including TI. The stress-response system (allostasis) is signaled by increased corticosteroid basal levels. In bird animal lines genetically selected for stress-induced corticosterone, there is a covariation between stress physiology and coping styles. Rabbit studies, in which the effects of TI are dissociated from those of induction per se, support the view that TI takes part in the homeostatic stress-response system. An increase of corticosterone is recorded just after the end of the induction procedure but not in the corresponding groups in which induction is followed by TI, suggesting a recovery process during TI. Similarly to corticosterone but in opposite direction, testosterone plasma levels decrease following induction and recover during TI. Recovery mechanisms are also suggested in two bird genotypes selected for long and short TI duration. The positive relation between corticosterone levels and TI duration has been confirmed after exogenous corticosterone administration.


SLAP lesions of the glenoid labrum diagnosed with MR imaging.
Tears of the superior portion of the glenoid labrum in patients without shoulder instability have recently been described. These tears, which include the "anchor" of the biceps tendon to the labrum, have been labeled "SLAP lesions" (superior labrum anterior to posterior). This study was performed to determine the magnetic resonance (MR) findings in patients with SLAP lesions. Retrospective review of the shoulder arthroscopy reports on patients who underwent MR imaging using a 1.5-T unit and subsequent arthroscopy by a single surgeon identified six patients with SLAP lesions (average age 36 years, range 17-65 years). MR images demonstrated atypical morphology indicative of tear in the superior portion of the labrum in four of the six patients, but only one tear had been identified preoperatively. Radiologists interpreting MR images of the shoulder should be aware of the MR findings of SLAP lesions as these tears can be a significant cause of patient disability and are difficult to diagnose clinically.


mTOR Overcomes Multiple Metabolic Restrictions to Enable HIV-1 Reverse Transcription and Intracellular Transport.
Cellular metabolism governs the susceptibility of CD4 T cells to HIV-1 infection. Multiple early post-fusion steps of HIV-1 replication are restricted in resting peripheral blood CD4 T cells; however, molecular mechanisms that underlie metabolic control of these steps remain undefined. Here, we show that mTOR activity following T cell stimulatory signals overcomes metabolic restrictions in these cells by enabling the expansion of dNTPs to fuel HIV-1 reverse transcription (RT), as well as increasing acetyl-CoA to stabilize microtubules that transport RT products. We find that catalytic mTOR inhibition diminishes the expansion of pools of both of these metabolites by limiting glucose and glutamine utilization in several pathways, thereby suppressing HIV-1 infection. We demonstrate how mTOR-coordinated biosyntheses enable the early steps of HIV-1 replication, add metabolic mechanisms by which mTOR inhibitors block HIV-1, and identify some metabolic modules downstream of mTOR as druggable targets for HIV-1 inhibition.


Listing all parsimonious reversal sequences: new algorithms and perspectives.
In comparative genomics studies, finding a minimum length sequences of reversals, so-called sorting by reversals, has been the topic of a huge literature. Since there are many minimum length sequences, another important topic has been the problem of listing all parsimonious sequences between two genomes, called the All Sorting Sequences by Reversals (ASSR) problem. In this article, we revisit the ASSR problem for uni-chromosomal genomes when no duplications are allowed and when the relative order of the genes is known. We put the current body of work in perspective by illustrating the fundamental framework that is common for all of them, a perspective that allows us for the first time to theoretically compare their running times. The article also proposes an improved framework that empirically speeds up all known algorithms.


The effect of progesterone on estrogen-induced uterine blood flow.
The effect of progesterone on estrogen-induced uterine blood flow was investigated in repeated experiments in seven nonpregnant, oophorectomized ewes with chronically implanted electromagnetic flow probes and catheters inserted into branches of the uterine arteries. Administered alone, progesterone has no effect on base-line uterine blood flow. Following intramuscular injection of progesterone (3 to 5 mg-per kilogram of body weight), peak uterine blood flow responses to 1 microng of estradiol-17beta were suppressed by 25 per cent compared to those of control animals. Direct intra-arterial infusion of progesterone, at concentrations sufficient to reproduce uterine venous levels observed in late pregnancy in the sheep, inhibited estrogen-induced uterine blood flow by 20 per cent. The findings support the hypothesis that progesterone modulates the estrogen-induced flow responses in both the pregnant and nonpregnant uterine vascular bed.


Benzo[a]pyrene-DNA adducts inhibit translocation by the gene 4 protein of bacteriophage T7.
Bacteriophage T7 gene 4 protein is an essential component of the T7 DNA replication system, acting as both a primase and a helicase. The gene 4 protein has been shown to translocate along single-stranded DNA in the 5'----3' direction, using an energy source for this movement the hydrolysis of nucleoside 5'-triphosphates, preferably dTTP. Thus, measuring the rate and extent of dTTP hydrolysis provides a means to directly measure translocation. We have determined that the hydrolysis of dTTP by the gene 4 protein is strongly inhibited by the presence of benzo[a]pyrene (B[a]P) adducts on the DNA. Time course experiments on adduct-containing DNA show that after an initial burst of hydrolysis, which parallels what is observed on unmodified DNA, further hydrolysis abruptly ceases. Addition of excess unmodified DNA does not restore the hydrolysis activity. These data suggest that the gene 4 protein is blocked and sequestered on the DNA at the site of the adduct. This was confirmed by experiments in which gene 4 protein preferentially protected the radiolabeled adduct-containing DNA but not randomly labeled M13 DNA. The gene 4 protein bound to the B[a]P-modified DNA was isolated, and the complex was found only to contain dTTP. These results have been used to formulate a model for gene 4 protein translocation in which we speculate that the power stroke for unidirectional movement along the single-stranded DNA is the displacement of dTDP by dTTP. Finally, we observe a constant ratio of DNA synthesis to dTTP hydrolysis regardless of the number of B[a]P adducts in the template suggesting that a significant portion of the inhibition of DNA synthesis is a direct consequence of the inhibition of gene 4 translocation.


Surgical management of peritoneal carcinosis: diagnosis, prevention and treatment.
Gastrointestinal and ovarian malignancies frequently recur with metastatic disease limited to the abdominal cavity. Due to full thickness penetration of tumor through bowel wall, spillage of tumor from lymphatic channels by surgical trauma or perforation of the tumor through the ovarian capsule, tumor cells are disseminated throughout the peritoneal surfaces either prior to or at the time of surgical removal of the primary tumor. In the past, diagnosis of recurrent cancer was difficult because no sensitive diagnostic test was available by which to image a small tumor volume present on peritoneal surfaces. Computerized tomography with intraperitoneal infusion of contrast can demonstrate tumor nodules not otherwise detectable. Intraperitoneal installation of I-131 labeled monoclonal antibody has allowed visualization of mucinous tumor on peritoneal surfaces not seen by any other radiologic test. Intraperitoneal chemotherapy has been shown to provide palliation in patients with small volume disease confined to peritoneal surfaces. Because of limited penetration of chemotherapy into large tumor nodules this treatment strategy has not been effective for bulky intraabdominal recurrent cancer. Cytoreductive surgery utilizing high voltage electrocautery and CO2 laser evaporation of tumor can make patients relatively disease free. These surgical technologies combined with postoperative intraperitoneal chemotherapy have been shown to be of benefit for selected patients with recurrent intraabdominal cancer. The wider application of these intraperitoneal chemotherapy treatments for patients in an adjuvant setting may be of value in preventing the occurrence of peritoneal carcinosis and in improving survival.


The Combination of Adipose-derived Schwann-like Cells and Acellular Nerve Allografts Promotes Sciatic Nerve Regeneration and Repair through the JAK2/STAT3 Signaling Pathway in Rats.
Schwann cells (SCs) combined with acellular nerve allografts (ANAs) effectively promote the regeneration and repair of peripheral nerves, but the exact mechanism has not been fully elucidated. However, the disadvantages of SCs include their limited source and slow rate of expansion in vitro. Previous studies have found that adipose-derived stem cells have the ability to differentiate into Schwann-like cells. Therefore, we speculated that Schwann-like cells combined with ANAs could profoundly facilitate nerve regeneration and repair. The aim of the present study was to investigate the cellular and molecular mechanisms of regeneration and repair. In this study, tissue-engineered nerves were first constructed by adipose-derived Schwann-like cells and ANAs to bridge missing sciatic nerves. Then, the rats were randomly divided into five groups (n = 12 per group): a Control group; a Model group; an ADSC group; an SC-L group; and a DMEM group. Twelve weeks postsurgery, behavioral function tests and molecular biological techniques were used to evaluate the function of regenerated nerves and the relevant molecular mechanisms after sciatic nerve injury (SNI). The results showed that adipose-derived Schwann-like cells combined with ANAs markedly promoted sciatic nerve regeneration and repair. These findings also demonstrated that the expression of neurotrophic factors (NFs) was increased, and the expression of Janus activated kinase2 (JAK2)/P-JAK2, signal transducer and activator of transcription-3 (STAT3)/P-STAT3 was decreased in the spinal cord after SNI. Therefore, these results suggested that highly expressed NFs in the spinal cord could promote nerve regeneration and repair by inhibiting activation of the JAK2/STAT3 signaling pathway.


Incorrect Surgical Counts: A Potential for Retained Surgical Items.
In the main operating rooms of a large academic hospital there was a report of 408 count discrepancies in 2015-2016 and 13 incidences of retained surgical items (RSIs). There was a lack of a consistent and standardized surgical count process among nurses. To reduce count discrepancies by 25%, prevent RSIs, and improve the compliance of the perioperative nursing team regarding the surgical count process. An evidence-based quality improvement project with a sample of 455 surgical procedures and 118 nurses. Data collection occurred over an eight-week period in 2018 using a Plan-Do-Study-Act (PDSA) methodology to study the effectiveness of the utilization of the Association of periOperative Registered Nurses (AORN) practice guidelines for the prevention of RSIs. The inclusion of risk reduction strategies such as the utilization of an AORN guideline whiteboard to record surgical items and the identification of high-risk items for retained device fragments or high-risk surgical items for RSIs resulted in the reduction of incorrect surgical counts by 71.43%, with no incidence of RSIs. Further, nurse compliance on surgical count practices improved significantly, F (5, 46) = 2.47, p = .046, PES = .21. The implementation of the AORN guidelines for perioperative surgical count practices by the perioperative nursing team provided an improved surgical count process. A system approach to performance improvement is needed to prevent RSIs.


Green sensitive spectrofluorimetric determination of pemetrexed as antineoplastic drug: Application in pharmaceutical dosage forms and spiked human plasma.
A recent antineoplastic medication is pemetrexed, this medicine is now being developed and produced on a large scale, thus approaches for quality control are urgently needed. Spectrofluorimetric guidelines for the simple estimation of pemetrexed were validated. Pemetrexed's assay depends on observations of its native fluorescence at wavelengths 275/450 nm and pH 4. The proposed approach was also used to identify the examined drug in both its formulation and in human plasma that had been spiked.


Replication of the abnormal niacin response in first episode psychosis measured using laser Doppler flowmeter.
Impaired sensitivity of the skin flush response to niacin is found in approximately 30% of patients with schizophrenia. Although the niacin response abnormality (NRA) may serve as a useful endophenotype for schizophrenia, few studies have directly replicated NRA in patients with first-episode psychosis (FEP). In total, 204 patients with FEP, 16 with psychotic mood disorder (PMD), and 68 healthy controls (HC) were included. The log10 (EC50 ) values represent the concentration of methyl nicotinate required to elicit a half-maximal blood flow (MBF) response, and the MBF value was calculated. The NRA was defined as having log10 (EC50 ) molar value above the 90% and an MBF value below the 60% of those in the HC group. In total, 13.7% of the FEP, 12.5% of the PMD, and 7.4% of the HC group met the definition of NRA. Significant differences were found in the log10 (EC50 ) values between the FEP and HC groups (p = .014) and in the MBF between the FEP and PMD groups (p = .011). Patients with FEP and NRA had more severe negative symptoms than those with a normal niacin response. These data represent the NRA in patients with FEP, defining a small subgroup of patients with early-phase psychosis possessing a clinically significant phospholipid-signaling defect.


Hsa_circ_0008344 Promotes Glioma Tumor Progression and Angiogenesis Presumably by Regulating miR-638/SZRD1 Pathway.
Hsa_circRNA_0008344 (circ_0008344) is a new glioma-related circular RNA. Our study aims to explore its functions in glioma tumor progression. Real-time quantitative PCR and western blotting were used to detect RNA and protein abundances. RNase R assay, actinomycin D assay, and subcellular fractionation method were performed to identify the features of circ_0008344. Cell-counting kit-8, 5-ethynyl-2'-deoxyuridine assays, transwell assays, tube formation assay, flow cytometry, and nude mice xenograft tumor model were performed. Target relationship was predicted by bioinformatics algorithms and confirmed by dual-luciferase reporter assay. Abundances of circ_0008344 and SUZ RNA binding domain containing 1 (SZRD1) were highly elevated, while miR-638 was downregulated in glioma tumors and cells. Circ_0008344 was identified as a stable circRNA with a circular structure. Silencing circ_0008344 could restrain glioma proliferation, migration, invasion, and angiogenesis. Circ_0008344 functioned as a sponge for miR-638. The negative regulation of circ_0008344 knockdown on glioma progression and angiogenesis could be reversed by miR-638 inhibitor. SZRD1 was a target of miR-318, and its overexpression overturned the inhibition effect of miR-638 mimic on glioma progression and angiogenesis. Meanwhile, we confirmed that circ_0008344 knockdown inhibited SZRD1 expression, and its effect was reversed by miR-638 inhibitor. Also, circ_00008344 knockdown suppressed glioma tumor growth. Circ_0008344 might contribute to glioma progression through miR-638/SZRD1 axis, which might be a novel pathology and treatment target in glioma.


Differential cytopathogenicity accompanying Mycoplasma pneumoniae infection of human lung fibroblasts maintained in newborn bovine serum or fetal bovine serum.
MRC-5 human lung fibroblasts maintained in Eagle's basal medium (BME) with either 10% fetal bovine serum (FBS) or 10% newborn bovine serum (NBS) did not respond identically to infection by Mycoplasma pneumoniae. Fibroblasts grown in NBS did not develop any cytopathic effect (CPE) when infected with M. pneumoniae, whereas those maintained in FBS developed a pronounced CPE. There was also a difference in sensitivity to infection for fibroblasts maintained in the two sera before the infection. Fibroblasts maintained in NBS, then transferred to FBS 48 h before infection, were still less sensitive to M. pneumoniae infection than cells maintained constantly in FBS. Mycoplasma pneumoniae attached comparably to the fibroblasts grown in the two sera, so the differences in CPE development could not be attributed to differences in mycoplasma attachment. Measurements of DNA, RNA, and protein syntheses of the fibroblasts grown in NBS and FBS indicate that the cells in NBS were growing more rapidly than those in FBS. A determination of the doubling times shows that the doubling time of cells in NBS was 44 h, whereas that of cells in FBS was 51 h. Polyacrylamide gel electrophoresis of samples of NBS and FBS showed significant differences in serum protein composition. The NBS had several protein bands that were lacking in the FBS. This study demonstrates the importance of serum effects in the study of M. pneumoniae infection.


CaMK-II oligomerization potential determined using CFP/YFP FRET.
Members of the Ca(2+)/calmodulin-dependent protein kinase II (CaMK-II) family are encoded throughout the animal kingdom by up to four genes (alpha, beta, gamma, and delta). Over three dozen known CaMK-II splice variants assemble into approximately 12-subunit oligomers with catalytic domains facing out from a central core. In this study, the catalytic domain of alpha, beta, and delta CaMK-IIs was replaced with cyan (CFP) or yellow fluorescent protein (YFP) for fluorescence resonance energy transfer (FRET) studies. FRET, when normalized to total CFP and YFP, reproducibly yielded values which reflected oligomerization preference, inter-subunit spacing, and localization. FRET occurred when individual CFP and YFP-linked CaMK-IIs were co-expressed, but not when they were expressed separately and then mixed. All hetero-oligomers exhibited FRET values that were averages of their homo-oligomeric parents, indicating no oligomeric preference or restriction. FRET for CaMK-II homo-oligomers was inversely proportional to the variable region length. FPs were monomerized (Leu221 to Lys221) for this study, thus eliminating any potential artifact caused by FP-CaMK-II aggregates. Our results indicate that alpha, beta, and delta CaMK-IIs can freely hetero-oligomerize and that increased variable region lengths place amino termini further apart, potentially influencing the rate of inter-subunit autophosphorylation.


Postnatal triiodothyronine concentrations in healthy preterm infants and in infants with respiratory distress syndrome.
Postnatal changes in triiodotyronine (T3) concentration were investigated in 12 preterm infants of 26-34 weeks of gestational age. Blood for measurement of T3 was obtained from the cord at delivery and from infants at 1 day of age and at weekly intervals for 4 weeks. Seven of the babies suffered from respiratory distress syndrome (RDS) and five were considred healthy. Gestational ages and body weight were comparable in both groups. In preterm infants with RDS, cord blood T3 concentration was significantly lower than that in cord blood of babies without RDS (22 +/- 2.6 versus 36 +/- 5 ng/dl, P less than 0.05). There was no significant rise in T3 concentration of RDS babies at 24 hr of age (22 +/- 2.6 versus 34.0 +/- 8 ng/dl, P greater than 0.05), and hypotriiodothyroninemia persisted for 3 weeks. At 4 weeks of age, T3 concentration in babies with RDS, although within the normal range (80-190 ng/dl), was significantly lower than that in the healthy preterm infants (110 +/- 10 versus 165 +/- 11 ng/dl, P less than 0.05). Postnatal T3 changes in healthy preterm infants wre characterized by the absence of the initial hypertriiodothyroninemia and by a gradual rise within the first month of life. The noted difference in the pattern of postnatal T3 changes in healthy preterm infants compared to full term infants may reflect thyroid immaturity. The machanism and the significance of the neonatal hypotriiodothyroninemia in RDS and its long term effects on the development of these babies remain to be investigated.


Mechanisms of long-term weight regain in patients undergoing sleeve gastrectomy.
Weight regain after bariatric surgery may be associated with behavioral, metabolic, or mechanical factors alone or in combination. The aim of this study was to investigate which factors are related to weight regain in the long-term after sleeve gastrectomy (SG). A retrospective case-control study with 40 patients undergoing SG (32 women, 8 men; age 42.9 ± 10.7 y; preoperative body mass index 35 ± 2.8 kg/m(2)), was performed. Patients were grouped according percentile->50% (cases) or <50% (controls)-of weight regain (%WR cutoff: 25% of weight loss). Weight history, anthropometry, glucose, insulin, homeostasis model assessment-estimated insulin resistance (HOMA-IR), thyroid-stimulating hormone, resting energy expenditure, body composition, dietary survey, psychological test, and physical activity were recorded. Residual gastric capacity was estimated using a radiologic method. RESULTS (MEDIAN [P25-P75]): The evaluation was conducted 38.5 mo (34-41 mo) after SG. Percent weight regain ranged from 2.7% to 129.2% (25.4% [13-37.1]). Patients in the higher %WR group had a greater residual gastric volume (252.7 ± 108.4 versus 148.5 ± 25.3; P < 0.05) and the estimated volume was significantly correlated with %WR (r = 0.673; P = 0.023). Significantly higher body mass index (P = 0.001), resting energy expenditure (P = 0.04), fasting insulin (P = 0.01), and HOMA-IR (P = 0.02) were observed in the higher %WR group. A higher fat intake and a trend toward higher total energy intake were observed in the group with greater %WR. Clinical or borderline levels of anxiety were more frequently observed in the higher %WR group (70% versus 30%; P = 0.01). Results from the present study demonstrated that the most important factor associated with long-term weight regain after SG was residual gastric volume. Additional prospective studies with larger numbers of patients are necessary to confirm our results.


"Bundling" HIV prevention: integrating services to promote synergistic gain.
Bundling is defined as the aggregation of services to increase effectiveness (i.e., creating synergy of effort). The purpose of this commentary is to review the utilization and potential benefits of bundling in its application to HIV prevention. Review of the literature to provide a broad perspective on the concept of bundling and specific examples of bundling in HIV prevention. Benefits, challenges and directions are considered. To be effective, bundling must offer strategic advantage: greater value, less cost. It provides an opportunity to target multiple risk behaviors simultaneously for synergistic gain. Technological advances including rapid HIV tests permit noninvasive sampling in clinical and non-clinical settings. Bundling of HIV prevention provides an opportunity to reach high-risk persons who are asymptomatic and/or may not otherwise seek care by eliminating barriers to prevention. We must implement programs that work and consider innovative approaches to stem the AIDS epidemic; bundling provides one such opportunity to create an efficient paradigm targeting multiple risk behaviors simultaneously.


Complete genome sequence of the haloalkaliphilic, obligately chemolithoautotrophic thiosulfate and sulfide-oxidizing γ-proteobacterium Thioalkalimicrobium cyclicum type strain ALM 1 (DSM 14477(T)).
Thioalkalimicrobium cyclicum Sorokin et al. 2002 is a member of the family Piscirickettsiaceae in the order Thiotrichales. The γ-proteobacterium belongs to the colourless sulfur-oxidizing bacteria isolated from saline soda lakes with stable alkaline pH, such as Lake Mono (California) and Soap Lake (Washington State). Strain ALM 1(T) is characterized by its adaptation to life in the oxic/anoxic interface towards the less saline aerobic waters (mixolimnion) of the stable stratified alkaline salt lakes. Strain ALM 1(T) is the first representative of the genus Thioalkalimicrobium whose genome sequence has been deciphered and the fourth genome sequence of a type strain of the Piscirickettsiaceae to be published. The 1,932,455 bp long chromosome with its 1,684 protein-coding and 50 RNA genes was sequenced as part of the DOE Joint Genome Institute Community Sequencing Program (CSP) 2008.


Disorders of the central nervous system: Insights from Notch and Nrf2 signaling.
The functional complexity of the central nervous system (CNS) is unparalleled in living organisms. It arises from neural crest-derived cells that migrate by the exact route, leading to the formation of a complex network of neurons and glial cells. Recent studies have shown that novel crosstalk exists between the Notch1 and Nrf2 pathways and is associated with many neurological diseases. The Notch1-Nrf2 axis may act on nervous system development, and the molecular mechanism has recently been reported. In this review, we summarize the essential structure and function of the CNS. The significance of interactions between signaling pathways and between developmental processes like proliferation, apoptosis and migration in ensuring the correct development of the CNS is also presented. We primarily focus on research concerning possible mechanism of interaction between Notch1 and Nrf2 and the functions of Notch1-Nrf2 in neurons. There may be a direct interaction between Notch1 and NRF2, which is closely related to the crosstalk that occurs between them. The significance and potential applications of the Notch1-Nrf2 axis in abnormal development of the nervous system are been highlighten. We also discuss the molecular mechanisms by which the Notch1-Nrf2 axis controls the apoptosis, antioxidant pathway and differentiation of neurons to modulate the development of the nervous system. This information will lead to a better understanding of Notch1-Nrf2 axis signaling pathways in the nervous system and may facilitate the development of new therapeutic strategies.


[Intraventricular morphine analgesia. Apropos of 4 cases, 1 with self-administration].
Intractable pain in four patients enduring disseminated cancer was treated by intraventricular morphine. For all these patients, previous efficiency of opiates therapy had been assessed by a positive trial of epidural injections of morphine. The latter method had to be stopped and a switch to intraventricular morphine was motivated in three cases by a local non-tolerance to the subarachnoid catheter. In one case, an intraventricular system was inserted at the first onset. In all cases, the intraventricular system consisted of a Holter type device, using a reservoir subcutaneously implanted in the frontal scalp and connected at right-angle with a catheter inserted in the lateral ventricle. Trial times were respectively of eight days, one month, two months and seven months, with a self administration system in one case. In comparison with the epidural and lumbar intrathecal administration of morphine, the authors insist upon the quality of analgesia obtained, the absence of respiratory depression, the comfort and minimal daily quantities of morphine injected (inferior to one mg daily in three cases). Enlightened by these four cases, the authors also discuss of relative importance of the spinal and brain mechanisms involved in morphine analgesia.


The prevalence and dynamics of Salmonella enterica IIIb 61:k:1,5,(7) in sheep flocks in Norway.
Fifty randomly selected sheep flocks from a region in central Norway were sampled in December 1999 to determine the flock prevalence of Salmonella enterica subspecies diarizonae serovar 61:k:1,5,(7) (S. IIIb 61:k:1,5,(7)). From each flock, 15-41 rectal swabs were collected from individual sheep of different age groups and examined for S. IIIb 61:k:1,5,(7). Positive flocks were visited again in January-April and each time, rectal swabs from the same animals were collected and examined for this specific serovar. Seven flocks (14%; 95% CI 6.3-27%) were positive for S. IIIb 61:k:1,5,(7) in December; in all, 10 sheep out of the 1233 (0.8%) were positive at the first sampling. From the seven positive flocks, six, five, six, and nine animals were positive in January, February, March, and April, respectively. Of the total 21 individual sheep tested positive from January to April, 15 were >2 years old (OR(ex)=3.26; 1.1-10.2). Six out of the seven positive flocks were large flocks (>117 ewes). Sharing of rams between flocks did not seem to be a risk factor for the presence of S. IIIb 61:k:1,5,(7) in a flock.


Enkephalin analogues with N-phenyl-N-(piperidin-2-ylmethyl)propionamide derivatives: Synthesis and biological evaluations.
N-Phenyl-N-(piperidin-2-ylmethyl)propionamide based bivalent ligands are unexplored for the design of opioid based ligands. Two series of hybrid molecules bearing N-phenyl-N-(piperidin-2-ylmethyl)propionamide derived small molecules conjugated with an enkephalin analogues with and without a linker (β-alanine) were designed and synthesized. Both bivalent ligand series exhibited remarkable binding affinities from nanomolar to subnanomolar range at both μ and δ opioid receptors and displayed potent agonist activities as well. The replacement of Tyr with Dmt and introduction of a linker between the small molecule and enkephalin analogue resulted in highly potent ligands. Both series of ligands showed excellent binding affinities at both μ (0.6-0.9nM) and δ (0.2-1.2nM) opioid receptors respectively. Similarly, these bivalent ligands exhibited potent agonist activities in both MVD and GPI assays. Ligand 17 was evaluated for in vivo antinociceptive activity in non-injured rats following spinal administration. Ligand 17 was not significantly effective in alleviating acute pain. The most likely explanations for this low intrinsic efficacy in vivo despite high in vitro binding affinity, moderate in vitro activity are (i) low potency suggesting that higher doses are needed; (ii) differences in experimental design (i.e. non-neuronal, high receptor density for in vitro preparations versus CNS site of action in vitro); (iii) pharmacodynamics (i.e. engaging signalling pathways); (iv) pharmacokinetics (i.e. metabolic stability). In summary, our data suggest that further optimisation of this compound 17 is required to enhance intrinsic antinociceptive efficacy.


Effect of cerebral neurite-stimulating protein on morphogenesis of organotypical culture of spinal ganglia.
We have extracted a cationic protein with a molecular weight of 15,000 kdalton from the hemispheres of rat and bovine brain. Addition of the protein to the nutrient medium of the organotypical culture of chick embryo spinal ganglia results in a considerable (2-2.5 fold) increase in the growth zone of the explants. The neurite-stimulating effect of the protein is observed at a concentration of 10 ng/ml. We observed an intensive longitudinal growth of neurites, an increase in their amount per unit area, a considerable intensification of ramification, and formation of strong anastomoses, numerous dense plexuses, and arcades. Fasciculi of neurites covered with glia are formed. The cerebral neurite-stimulating protein is evidently one of the neuron-growth factors regulating development of the nervous system in the body.


Immunohistochemical localization of inhibin subunits in the testis of the bull.
The differential localization of the inhibin beta subunits betaA and betaB in the testis of adult bull was studied using specific monoclonal and polyclonal primary antibodies. Inhibin betaA- and betaB-subunits were localized only in the Sertoli cells. The inhibin betaA-subunit was observed in the cytoplasm while the betaB-subunit was localized in the nucleus. No specific findings depending on spermatogenic stages were observed among the seminiferous tubules. Moreover, the inhibin alpha-subunit was not detected in the testis of the bulls. In addition, no inhibin subunits were detected in the Leydig cells and spermatogenic cells. These findings indicate the presence of betaA- and betaB-subunits in the bull, which may suggest a possibility that activin is produced and/or stored in the Sertoli cells and regulates spermatogenesis in an autocrine/paracrine manner. Moreover, the inhibin betaB-subunit may be produced in the nucleus but the functional meaning of this is not yet clear.


Endophthalmitis after pars plana vitrectomy: a New Zealand experience.
To describe the clinical course and estimate the incidence of endophthalmitis after pars plana vitrectomy in New Zealand. A retrospective analysis was performed on all cases of culture-positive endophthalmitis after vitreoretinal surgery over a 10-year period. Five cases of culture-positive endophthalmitis were identified between 1993 and 2002. During this interval, 10,397 vitrectomies were performed, equating to an overall incidence of 0.048%. All patients presented within 7 days of surgery. Endophthalmitis after pars plana vitrectomy is uncommon but is associated with a poor functional outcome.


Effect of information literacy skills on university students' information seeking behaviour and lifelong learning.
This study investigated the influence of information literacy (IL) skills on students' information seeking behaviour and lifelong learning skills in Higher Educational institutions in Ghana, with particular reference to the University of Cape Coast (UCC). Using a mixed method approach, 278 students from the College of Education Studies, UCC were sampled for the study. The components of the American College and Research Library (ACRL) model was used to measure the information literacy competence level of the students. A content and bibliographic evaluation of students' research projects were conducted using document analysis. Pearson product-moment correlation coefficient was used to determine the association between information literacy skills and information seeking behaviour of students from data collected through questionnaires, interviews and document analysis. The results revealed that respondents had developed substantial skills in information literacy and lifelong learning skills and thus adopted positive attitudes in information seeking. The paper concludes that majority of the students were confident users of information. The study recommends that academic libraries should make available a wide array of information sources and deliberately run programmes to introduce students to those information sources as a way of building their competency levels in information literacy.


Long-term evaluation of once daily vigabatrin in drug-resistant partial epilepsy.
The purpose of this study was to evaluate on an open basis the long-term efficacy and safety of vigabatrin in drug-resistant partial epilepsy as add-on therapy, administered on a once daily basis. Thirty-five patients entered the study. Twenty patients (57%) responded to therapy and are still on drug. This efficacy is in agreement with that seen in double-blind controlled studies on twice daily dose schedules. There did not appear to be any loss of efficacy with continued treatment at this dose regimen in patients responding favourably to the drug. The once daily dosing schedule was well tolerated and side effects were usually mild and always reversible. Vigabatrin seems to be a valuable therapeutic addition for patients with partial seizures resistant to standard anti-epileptic drugs.


A surviving infant with sirenomelia (Mermaid syndrome) associated with absent bladder.
The authors report a case of a surviving infant with sirenomelia (Mermaid syndrome). The child is now 4 years of age. The authors believe that this is only the fourth reported case of an infant with sirenomelia surviving beyond the neonatal period and the first associated with absent bladder. The abnormal distal aorta shown in this case supports the theory that sirenomelia is an extreme form of caudal dysgenesis rather than occurring secondary to vascular steal.


Cigarettes, a skin killer! Cigarette smoke may cause ferroptosis in female skin.
Skin exposure to tobacco smoke is closely related to skin aging. Ferroptosis is an iron-dependent form of regulated cell death driven by the accumulation of lipid peroxides to levels sufficient to trigger cell death. However, few studies have examined ferroptosis in skin-related diseases. This study searched for differentially expressed genes by analyzing gene expression data downloaded from the Gene Expression Omnibus. Ferroptosis-related genes were obtained by analyzing the FerrDb database. We also investigated the regulatory mechanism of ferroptosis-related genes by enrichment analysis and constructing gene-miRNA and gene-transcription factor networks. Based on these analyses, exposure to cigarette smoke can cause ferroptosis in female skin. Ferroptosis-associated genes might be regulated by 17 miRNAs and 20 TFs. Finally, we found ferroptosis in the skin of women exposed to cigarette smoke, and the results provide an important theoretical basis for future research and anti-aging treatment of skin.


Value of intraoperative resistive index in kidney transplant.
The value of the resistive index (RI) obtained by echo color doppler evaluation of the transplanted kidney is still not well established. Many authors consider the RI to be nonspecific sign of rejection, acute tubular necrosis, or urinary tract obstruction, but its specificity remains low. In this paper, we report our experience with RI determinations in 34 consecutive kidney transplants at different times namely: perioperatively, at 24 hours, at 3 days, at 6 and at 9 days posttransplant. In all patients intraoperative RI was normal. RI increased significantly after transplantation in 10 patients who eventually developed a complication: delayed function, acute rejection, and spontaneous kidney ruptures. This increment from the baseline value was already significant at 24 hours after the kidney transplant, indicating a possible posttransplant complication (0.62 +/- 0.07 vs 0.76 +/- 0.04; P = .0004). We conclude that the value of RI in the early posttransplant phase should be considered an important aid for the early diagnosis of posttransplant complications.