The magnetic field induced phase separation in a model of a superconductor with local electron pairing.
We have studied the extended Hubbard model with pair hopping in the atomic limit for arbitrary electron density and chemical potential and focus on paramagnetic effects of the external magnetic field. The Hamiltonian considered consists of (i) the effective on-site interaction U and (ii) the intersite charge exchange interactions I, determining the hopping of electron pairs between nearest-neighbour sites. The phase diagrams and thermodynamic properties of this model have been determined within the variational approach (VA), which treats the on-site interaction term exactly and the intersite interactions within the mean-field approximation. Our investigation of the general case shows that the system can exhibit not only the homogeneous phases-superconducting (SS) and non-ordered (NO)-but also the phase separated states (PS: SS-NO). Depending on the values of interaction parameters, the PS state can occur in higher fields than the SS phase (field induced PS). Some ground state results beyond the VA are also presented.


The role of intermediaries in connecting community-dwelling adults to local physical activity and sport: A scoping review protocol.
Introduction: Physical inactivity is a major global issue affecting health. Promoting, supporting and encouraging physical activity amongst community-dwelling adults is essential, especially in primary care services where the majority of healthcare contacts take place. An intermediary, a professional who supports individuals to connect with appropriate community and voluntary services with the goal of improving health and wellbeing, may be a promising method to establish a connection to local physical activity; however the process has been poorly described to date. Objective: The objective of this scoping review will be to identify and summarise the literature describing the process of connecting community-dwelling adults to an intermediary, the processes (role, practice and procedure) of an intermediary in connecting these adults to local physical activity and sport opportunities, and to map these processes of connection to outcomes. Methods: This scoping review will be conducted in accordance with the scoping review methodology of the Joanna Briggs Institute. A comprehensive search strategy will identify relevant studies in Embase, Medline, Web of Science and CINAHL, along with a structured grey literature search. Studies which describe an intermediary connecting community-dwelling adults (aged ≥18 years) to a local physical activity and/or sport opportunity or other similar resource will be included. Data will be charted and narratively summarised. Intermediary processes will be mapped to outcomes related to physical activity, and the PAGER (patterns, advances, gaps, evidence for practice and research recommendations) framework will be used to identify evidence gaps and research recommendations. Conclusions: This scoping review will be the first to describe the process of an intermediary connecting community dwelling adults to local physical activity. This review will identify, map and summarise the existing research on the processes and outcomes. The results will also identify any evidence gaps and will guide future research.


Pseudotargeted metabolomics-based random forest model for tracking plant species from herbal products.
The "one-to-multiple" phenomenon is prevalent in medicinal herbs. Accurate species identification is critical to ensure the safety and efficacy of herbal products but is extremely challenging due to their complex matrices and diverse compositions. This study aimed to identify the determinable chemicalome of herbs and develop a reasonable strategy to track their relevant species from herbal products. Take Astragali Radix-the typical "one to multiple" herb, as a case. An in-house database-driven identification of the potentially bioactive chemicalome (saponins and flavonoids) in AR was performed. Furthermore, a pseudotargeted metabolomics method was first developed and validated to obtain high-quality semi-quantitative data. Then based on the data matrix, the random forest algorithm was trained to predict Astragali Radix species from commercial products. The pseudotargeted metabolomics method was first developed and validated to obtain high-quality semi-quantitative data (including 56 saponins and 49 flavonoids) from 26 batches of AR. Then the random forest algorithm was well-trained by importing the valid data matrix and showed high performance in predicting Astragalus species from ten commercial products. This strategy could learn species-special combination features for accurate herbal species tracing and could be expected to promote the traceability of herbal materials in herbal products, contributing to manufacturing standardization.


Endovascular and Antithrombotic Treatment in Blunt Cerebrovascular Injuries: A Systematic Review and Meta-Analysis.
Ischemic stroke has been estimated to occur in up to 26% of patients with blunt cerebrovascular injury (BCVI). Antithrombotic therapy (AT) may be used for stroke prevention, but the role of endovascular treatment (ET) remains unclear. We systematically reviewed the literature on AT and ET for the treatment of patients with BCVIs. PubMed, EMBASE, Web of Science, and Cochrane were searched upon the PRISMA guidelines to include studies reporting the use of ET in BCVI patients. Post-ET neurologic outcomes, radiographic responses, and complication rates were assessed. A fixed-effect model meta-analysis was performed to compare treatment-related post-BCVI ischemic stroke rates between AT and ET protocols. We included 16 studies comprising 352 patients undergoing ET for BCVI. Mean post-ET rates of good neurologic outcomes and radiologic responses were 86.9% (range, 63.6-100%) and 94.0% (range 57.1-100%), respectively. Mean post-ET complication rate was 5.2% (range, 0-66.7%). Seven studies compared the roles of AT (delivered in 805 patients) and ET (performed in 235 patients) for preventing the onset of post-BCVI ischemic strokes. No significant difference in rates of post-BCVI ischemic stroke was found between patients receiving AT vs patients undergoing ET (OR 0.71, 95% CI: 0.35-1.42, p = 0.402). AT and ET may be comparable in preventing the occurrence of ischemic stroke following BCVIs. AT may be preferred as the less-invasive first-line therapy, but ET showed favorable rates of post-treatment clinical and radiologic outcomes, coupled with low rates of treatment-related complications.


Routine testing of liver function before and after elective laparoscopic cholecystectomy: is it necessary?
Liver function tests (LFTs) include alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), and bilirubin. The role of routine testing before and after laparoscopic cholecystectomy was evaluated in this study. A total of 355 patients were retrospectively analyzed by examining the LFTs the day before, the day after, and 3 weeks after the surgery. The Wilcoxon signed-rank test and Student t test were performed to determine statistical significance. Alterations in the serum AST, ALT, and GGT were seen on the first postoperative day. Minor changes were seen in bilirubin and ALP. An overall disturbance in the LFTs was seen in more than two-thirds of the cases. Repeat LFTs performed after 3 weeks on follow-up were found to be within normal limits. Mild-to-moderate elevation in preoperative LFTs may not be associated with any deleterious effect, and, in the absence of clinical indications, routine preoperative or postoperative liver function testing is unnecessary.


Combinatory responses of proinflamamtory cytokines on nitric oxide-mediated function in mouse calvarial osteoblasts.
Combinatory responses of proinflamamtory cytokines have been examined on the nitric oxide-mediated function in cultured mouse calvarial osteoblasts. Interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) induced iNOS gene expression and NO production, although these actions were inhibited by L-NG-monomethylarginine (L-NMMA) and decreased alkaline phosphatase (ALPase) activity. Furthermore, NO donors, sodium nitroprusside (SNP) and NONOate dose-dependently elevated ALPase activity. In contrast, transforming-growth factor-beta (TGF-beta) decreased NO production stimulated by IL-1beta, TNF-alpha and interferon-gamma (IFN-gamma). iNOS was expressed by mouse calvarial osteoblast cells after stimulation with IL-1beta, TNF-alpha, and IFN-gamma. Incubation of mouse calvarial osteoblast cells with the cytokines inhibited growth and ALPase activity. However, TGF-beta-treatment abolished these effects of IL-1beta, TNF-alpha and IFN-gamma on growth inhibition and stimulation of ALPase in mouse calvarial osteoblast cells. In contrast, IL-1beta, TNF-alpha, and IFN-gamma exerted growth-inhibiting effects on mouse calvarial osteoblast cells which were partly NO-dependent. The results suggest that NO may act predominantly as a modulator of cytokine-induced effects on mouse calvarial osteoblast cells and TGF-beta is a negative regulator of the NO production stimulated by IL-1beta, TNF-alpha and IFN-gamma.


Oxysterols as non-genomic regulators of cholesterol homeostasis.
Tight regulation of cellular and plasma cholesterol is crucial to proper cellular functioning because excess free cholesterol is toxic to cells and is associated with atherosclerosis and heart disease. Cellular cholesterol homeostasis is regulated by enzymatically formed oxygenated cholesterol derivatives termed oxysterols. Although the effects of oxysterols on transcriptional pathways are well described, the non-transcriptional mechanisms through which oxysterols acutely modulate cellular cholesterol levels are less well understood. We present emerging evidence suggesting that the membrane biophysical properties of oxysterols underlie their acute cholesterol-regulatory functions and discuss the relevance of these acute effects to cholesterol overload in physiological and pathophysiological states.


Pulsar radiation mechanisms.
Gamma rays produced by electrons accelerated in the strong magnetic fields of neutron stars annihilate to electron-positron pairs. This leads to a two-stream situation, which results in bunching and coherent radio emission.


Exploiting the performance of dictionary-based bio-entity name recognition in biomedical literature.
Bio-entity name recognition is the key step for information extraction from biomedical literature. This paper presents a dictionary-based bio-entity name recognition approach. The approach expands the bio-entity name dictionary via the Abbreviation Definitions identifying algorithm, improves the recall rate through the improved edit distance algorithm and adopts some post-processing methods including Pre-keyword and Post-keyword expansion, Part of Speech expansion, merge of adjacent bio-entity names and the exploitation of the contextual cues to further improve the performance. Experiment results show that with this approach even an internal dictionary-based system could achieve a fairly good performance.


[Effects of a drug misuse and abuse prevention program on knowledge, attitude, and preventive behaviors related to drug misuse and abuse, and depression in low-income elderly women].
This study was conducted to determine the effects of a drug misuse and abuse prevention program on knowledge, attitude, and preventive behaviors related to drug misuse and abuse, and depression in low-income elderly women in the urban area. The design of this study was a nonequivalent control group pretest-posttest design. The subjects consisted of 26 in the experimental group and 23 in the control group. The program was performed for about 1 hour, once a week for 5 weeks. Data was analyzed by the SAS(ver.8.02) computer program, and it included descriptive statistics, Fisher's exact test, Mann-Whitney U test, Wilcoxon signed ranks test, and ANCOVA. There were statistically significant differences in knowledge, attitude, and preventive behaviors related to drug misuse and abuse, and depression between the experimental group and the control group. This study showed that this prevention program of drug misuse and abuse is appropriate for low-income elderly women, Therefore this program is recommended as a nursing intervention strategy for the elderly.


Design and synthesis of a new type of non steroidal human aromatase inhibitors.
The structure-activity relationship study of one of recently described aromatase inhibitors, compound 1 (MR20814), allowed us to design some related derivatives as potential new inhibitors. Among those we synthesized, chlorophenylpyridylmethylenetetrahydroindolizinone 5 (MR20492) exhibited in vitro a ten-fold higher inhibition of the enzyme (IC50 = 0.2 +/- 0.0 microM and Ki = 10.3 +/- 3.3 nM).


Antiretroviral treatment initiation does not differentially alter neurocognitive functioning over time in youth with behaviorally acquired HIV.
Although youth living with behaviorally acquired HIV (YLWH) are at risk for cognitive impairments, the relationship of impairments to HIV and potential to improve with antiretroviral therapy (ART) are unclear. This prospective observational study was designed to examine the impact of initiation and timing of ART on neurocognitive functioning in YLWH in the Adolescent Medicine Trials Network for HIV/AIDS Interventions. Treatment naïve YLWH age 18-24 completed baseline and four additional assessments of attention/working memory, complex executive, and motor functioning over 3 years. Group 1 co-enrolled in an early ART initiation study and initiated ART at enrollment CD4 >350 (n = 56); group 2 had CD4 >350 and were not initiating ART (n = 66); group 3 initiated ART with CD4 <350 (n = 59) per standard of care treatment guidelines at the time. Treatment was de-intensified to boosted protease inhibitor monotherapy at 48 weeks for those in group 1 with suppressed viral load. Covariates included demographic, behavioral, and medical history variables. Analyses used hierarchical linear modeling. All groups showed improved performance with peak at 96 weeks in all three functional domains. Trajectories of change were not significantly associated with treatment, timing of treatment initiation, or ART de-intensification. Demographic variables and comorbidities were associated with baseline functioning but did not directly interact with change over time. In conclusion, YLWH showed improvement in neurocognitive functioning over time that may be related to practice effects and nonspecific impact of study participation. Neither improvement nor decline in functioning was associated with timing of ART initiation or therapy de-intensification.


Monitoring of deoxynivalenol and zearalenone in cereals and cereal products from the state of Saxony-Anhalt, Germany.
A Fusarium and Fusarium toxin monitoring programme has been established within the food and feed control authorities of Saxony-Anhalt for the 2001-2003 period. The first results of the deoxynivalenol analyses of cereals and cereal products with assured origin in this federal state, showed a contamination rate of 42% for wheat and wheat products. The contamination incidence reached only 14% in rye and rye products. Zearalenone couldn't be detected at all in the analyzed samples.


Prediction of raised intracranial pressure complicating severe traumatic brain injury in children: implications for trial design.
To describe current patterns of management of raised intracranial pressure (ICP) in traumatic brain injury relevant to clinician buy-in to possible randomized controlled trials of treatments of raised ICP. To examine the feasibility of early identification of children at sufficient risk of developing raised ICP to permit a uniform approach between centers to the initiation of ICP monitoring. This would permit quantification of ICP elevation and enrollment as appropriate to randomized controlled trials of raised ICP interventions. Logistic regression modeling of death before pediatric intensive care unit discharge and decision tree and logistic regression of development of raised ICP through analysis of a prospectively collected, standardized, national data set. Pediatric intensive care units in the United Kingdom and Eire. Patients were 501 children <16 yrs of age primarily admitted to intensive care unit for management of traumatic brain injury in the United Kingdom and Eire between February 2001 and August 2003. None. The data analyzed included demographic, acute physiologic, and cranial imaging variables. Death was associated with both raised ICP and the nonmeasurement of ICP. In a subset of 199 patients, an empirically derived decision rule predicted the development of raised ICP at any point during ICU admission with sensitivity of 73% and specificity of 74% (positive predictive value 82% and negative predictive value 63%). Logistic regression modeling performed comparably. The decision rule also predicted raised ICP in 20% of children not undergoing ICP monitoring. Simple models based on early clinical data may predict the development of raised ICP sufficiently well to encourage a consistent approach between centers to initiation of ICP monitoring. We estimate studies designed to detect reductions in ICU mortality will require >320 children per arm, although this figure may be higher if more conservative assumptions are made.


The distribution of keratin type intermediate-sized filaments in so-called mixed tumour of the skin.
Epithelial cells can be distinguished from various non-epithelial cells by the presence of keratin-type intermediate-sized filaments, which can be detected by immunofluorescence microscopy, using antibodies to alpha-keratin. In the present study, two types of antibodies were obtained. One of them was specific for alpha-keratin (mol. wt. 49,000 to 69,000 daltons) in whole epidermis, and the other for alpha-keratin (mol. wt. 62,000 and 69,000 daltons) in prickle and granular cells but not in basal cells. Four cases of so-called mixed tumour of the skin were studied by immunofluorescence microscopy using these antibodies. Tumour cells nests of cuboidal and polygonal cells, tubular structures and keratinous cysts reacted with these antibodies, as did individually-dispersed tumour cells within the myxoid and chondroid matrix. These results indicate that all the tumour cells of the so-called mixed tumour of the skin are of epithelial origin. Differences in staining intensity between these tumor cells and their specificity for these two antibodies are discussed with reference to keratin differentiation in tumour cells.


Expression of poliovirus nonstructural proteins in Escherichia coli cells. Modification of membrane permeability induced by 2B and 3A.
The poliovirus nonstructural proteins 2B, 2C, 2C3A, 2C3AB, 3A, and 3AB have been cloned and efficiently expressed in Escherichia coli cells. Each individual protein, or combinations of some of them, were cloned using polymerase chain reaction techniques and correspond to the genuine poliovirus protein plus an additional methionine. The system used to express them uses pET vectors containing the promoter of gene 10 of phage T7. Expression of protein 2C in BL21 (DE3) pLysS cells, which express the T7 lysozyme, is not toxic, and the bacteria synthesize this protein for several hours after induction. In contrast, the expression of proteins 2B, 3A, or 3AB is not tolerated by BL21 (DE3) pLysS cells which could make them only for a limited period of time. Protein 3AB was particularly toxic and induced a rapid lysis of the recombinant clone after its induction with isopropyl-1-thio-beta-D-galactopyranoside alone or with both isopropyl-1-thio-beta-D-galactopyranoside and rifampicin. Further analyses showed that 3AB induced profound modifications in membrane permeability to o-nitrophenyl-beta-D-galactopyranoside, labeled uridine, and nonpermeant translation inhibitors. Cloning and expression of proteins 2B, 3A, and 3AB in BL21 (DE3) cells that do not contain the T7 lysozyme lead to a more sustained expression of these proteins without detectable cell lysis. Changes in permeability to low molecular weight compounds such as radioactive uridine, o-nitrophenyl-beta-D-galactopyranoside, and hygromycin B readily appeared upon induction of 2B, 3A, and 3AB. Our results indicate that the poliovirus nonstructural polypeptides 2B and 3A (or 3AB) are lytic for the bacteria. In fact, both proteins 2B and 3A contain hydrophobic domains in a potential amphipathic helix; this is one characteristic shared with a number of membrane-active peptides.


Purification and biochemical characterization of a novel protein-tongue cancer chemotherapy resistance-associated protein1 (TCRP1).
Multidrug resistance is a major obstacle to successful treatment of oral squamous cell carcinoma (OSCC). Lately, we found a novel human gene named tongue cancer chemotherapy resistance-associated protein1 (TCRP1) in the tongue cancer multi-drug resistance cell line (Tca8113/PYM) established by us. In this study, we focus on recombinant expression, purification, and biochemical characterization of TCRP1. After molecular cloning and purification of the gene encoding the 24-kDa protein, a mouse polyclonal antibody against TCRP1 was prepared, and the specialty of the antibody was confirmed by Western blot. The cell proliferation was evaluated by MTS assay and DNA damage was determined by comet assay, the results indicated that this protein especially mediated the cell's resistance to cisplatin; it was associated with its role of providing protection against DNA damage. We also found that TCRP1 expression was increased in cisplatin-resistant carcinoma cell lines (Tca/PYM and A549/DDP), but not in cisplatin-sensitive MDR cell lines (MCF-7/5-Fu), compared with their parental counterparts by Western blot analysis. Immunofluorescence and immunohistochemical analysis showed TCRP1 is mainly expression in cytoplasmic, the Mann-Whitney U test exhibited that TCRP1 positive patients predicted the worst sensitive with cisplatin of OSCC patients. All these findings suggest that TCRP1 is a novel cisplatin-resistant protein which is mainly localized in the cytoplasm and can mediate cisplatin resistance against DNA damage; the expression level of TCRP1 in patients with OSCC may be useful as an indicator of therapeutic efficacy of the sensitivity to cisplatin.


Molecular modeling and expression analysis of a MADS-box cDNA from mango (Mangifera indica L.).
MADS-box genes are a large family of transcription factors initially discovered for their role during development of flowers and fruits. The MADS-box transcription factors from animals have been studied by X-ray protein crystallography but those from plants remain to be studied. In this work, a MADS-box cDNA from mango encoding a protein of 254 residues was obtained and compared. Based on phylogenetic analysis, it is proposed that the MADS-box transcription factor expressed in mango fruit (MiMADS1) belongs to the SEP clade of MADS-box proteins. MiMADS1 mRNA steady-state levels did not changed during mango fruit development and were up-regulated, when mango fruits reached physiological maturity as assessed by qRT-PCR. Thus, MiMADS1 could have a role during development and ripening of this fruit. The theoretical structural model of MiMADS1 showed the DNA-binding domain folding bound to a double-stranded DNA. Therefore, MiMADS1 is an interesting model for understanding DNA-binding for transcriptional regulation.


Clinical issues in antibody design.
Antibody genes can now be cloned and expressed in various ways to give new versions of antibodies that possess reduced immunogenicity, improved affinity, altered size, increased avidity and novel effector functions. The task for any clinical application is, first, to define a relevant target, and then to design the optimal antibody-based therapeutic molecule to react with that target. This article reviews these improved antibody-based molecules and examines their role in cancer therapy.


[Not Available].
Ochratoxin A (OTA) is an important food and feed contaminant with potential adverse effects in humans and animals. In view of present discussions on limit values for OTA in foods, essential elements of a toxicological risk assessment are outlined. The exposure situation in Europe is now well documented. The data base, with respect to a characterization of hazard and dose-response relationships, allowed to calculate a provisional tolerable daily intake for OTA suited to protect the consumer against undesirable toxic effects. Nonetheless, further research on OTA is indicated in view of unresolved issues regarding the following points: 1. mechanisms of action (mode of genotoxicity, role of bioactivation/metabolism, identification of DNA-adducts and dose-dependency); 2. combinations of OTA and other mycotoxins (studies of relevant mixtures/conditions); 3. individual susceptibility and/or situation-based vulnerability. Better information on mechanistic aspects of mycotoxin-induced toxicities will further improve our knowledge on the "margin of safety" between a given exposure and a potential impairment of human health.


Synergism between antibody and neutrophils in the ruminant mammary gland.
Immunological activities of the mammary gland are important both as a means of transferring immunity from mother to young and for defending the mammary gland itself against infection. The presence of immunoglobulins G1, G2 and A, and of neutrophils, macrophages and complement in the ruminant mammary gland is described, in particular the synergistic role of antibody and neutrophils is discussed and studies of immunization against staphylococcal mastitis are outlined.


SIRT6: therapeutic target for nonalcoholic fatty liver disease.
Recently, Hou et al. shifted the research focus from the function of nuclear sirtuin (SIRT)6 to that of cytoplasmic SIRT6, which deacetylates and activates long-chain acyl-CoA synthase 5 (ACSL5). Their findings provide mechanistic insight into the role of cytoplasmic SIRT6 in fatty acid oxidation, acting as a therapeutic target for combating nonalcoholic fatty liver disease (NAFLD).


Diet in pregnant women that delivered prematurely and preterm newborn's bone status.
Inadequate maternal dietary pattern has been associated to negative pregnancy and fetal outcomes. With this study, we aimed to evaluate the adequacy of diet in pregnant women that delivered prematurely and its possible correlations with bone status of preterm newborns. We prospectively enrolled women who delivered prematurely (≤than 34 gestational weeks) and their newborns (Neonatal Intensive Care, University Hospital of Padova) from January 2017 to May 2018. Maternal nutritional status and diet supplementations were assessed using a validated questionnaire. The preterm newborns were evaluated with anthropometric measurements and bone status by Quantitative Ultrasound of the second metacarpal bone within 72 h from birth. One hundred and eighty mothers and 202 preterm newborns were evaluated. The mothers assumed more calories, proteins, total lipids and simple sugars compared to the revised National Guidelines. The intake of calcium, phosphorus and Vitamin D was inadequate despite the use of multivitamin supplements. The mothers assumption of vitamin D and zinc positively correlated with bone status and mothers with very low intake of vitamin D during gestation (<7 µg/die) had preterm newborns with a worst bone status at birth compared to those with a better intake (>7 µg/die). Nutrition of pregnant women could be improved and maternal intakes of Vitamin D and zinc positively correlated with preterm newborn's bone status.


Patterns of biomarker expression in patients treated with primary endocrine therapy - a unique insight using core needle biopsy tissue microarray.
Prediction of response to primary endocrine therapy (PET) in older women is based on measurement of oestrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor (HER)-2. This study uses a unique method for construction of core needle biopsy (CNB) tissue microarray (TMA), to correlate expression of a panel of 17 biomarkers with clinical outcome, in patients receiving PET. Over 37 years (1973-2010), 1758 older (≥ 70 years) women with operable primary breast cancer were managed in a single institution. Of these, 693 had sufficient good-quality CNB to construct TMA, of which 334 had ER-positive tumours treated by PET with a minimum of 6-month follow-up. A panel of biomarkers was measured by immunohistochemistry (ER, PgR, HER2, Ki-67, p53, CK5/6, CK 7/8, EGFR, BCL-2, MUC1, VEGF, LKB1, BRCA1, HER3, HER4, PTEN and AIB1). Expression of each biomarker was dichotomised into 'low' or 'high' based on breast cancer-specific survival (BCSS). From the panel of biomarkers, multivariate analysis showed: High ER (p = 0.003) and PgR (p = 0.002) were associated with clinical benefit of PET at 6 months, as opposed to progressive disease. High ER (p = 0.0023), PgR (p < 0.001) and BCL-2 (p = 0.043) and low LKB1 (p = 0.022) were associated with longer time to progression. High PgR (p < 0.001) and low MUC1 (p = 0.021) were associated with better BCSS. Expression of other biomarkers did not show any significant correlation. In addition to ER and PgR; MUC1, BCL-2 and LKB1 are important in determining the outcome of PET in this cohort.


Partial splenectomy for portal hypertension in cystic fibrosis related liver disease.
To review the middle- and long-term effects of partial splenectomy (PS) on portal hypertension (PHT) and its complications in patients with cystic fibrosis (CF) related liver disease risky PHT. Over a 20 years period, 19 patients aged 7-23 years underwent partial PS for massive splenomegaly, hypersplenism, and/ or severe PHT. In all but three cases, PHT and hypersplenism have improved for long periods. Noticeable improvement of hepatic tests occurred simultaneously. In all patients PS resolved abdominal discomfort. Fifteen patients are alive and a stabilization of the liver disease occurred with a follow-up of 1-20 years (mean 7.9). One patient died following respiratory insufficiency 10 years after PS although PHT was stable. Manifestations recurred in 2 patients 5 and 6 years after PS. In two patients, the course of the disease evolved to hepatic insufficiency without recurrence of PHT 3 and 8 years after PS. PS did not give the expected results in three cases only, in which PHT was not modified or reoccurred during the following year. No severe complication was observed. Early (three patients) or late (one patient) eventration required surgical procedure. Our results show that PS is a reliable and well-tolerated technique. Therefore, it is a therapeutic option for the management of PHT in CF patients with a preserved liver function. It can prevent and significantly delay a liver transplantation and its constraints.


Population cytogenetics of folate-sensitive fragile sites. II. Autosomal rare fragile sites.
The frequencies of folate-sensitive autosomal rare fragile sites (ARFS) were compared in populations of mentally retarded, mentally subnormal, and mentally normal children and of patients referred for diagnostic chromosome study. The frequencies did not differ significantly. Altogether, an autosomal rare fragile site was found in 16 of 1,445 individuals (1 in 90). Of six different folate-sensitive ARFS detected, the most common one was FRA9A, with a frequency of 1 in 241 individuals. In addition, FRA17A, classified as a distamycin A-inducible fragile site, was found with a frequency of 1 in 206. It was regarded as a spontaneously expressive fragile site. In 19 families in which transmission of an autosomal rare fragile site was studied, the mother was the carrier in 16 families and the father, in one family. The mean percentage (+/- SD) of cells expressing ARFS in 55 individuals was 19% (+/- 11.4). The age did not affect the rate of expression. When the rate of expression was calculated separately in a group of mentally retarded (mean = 23.4%) and in a group of mentally normal individuals (mean = 16.0%), the difference was statistically significant.


Gene editing of non-coding regulatory DNA and its application in crop improvement.
The development of the clustered regularly interspaced short palindromic repeats/CRISPR-associated protein (CRISPR/Cas) system has provided precise and efficient strategies to edit target genes and generate transgene-free crops. Significant progress has been made in the editing of protein-coding genes; however, studies on the editing of non-coding DNA with regulatory roles lags far behind. Non-coding regulatory DNAs, including those which can be transcribed into long non-coding RNAs (lncRNAs), and miRNAs, together with cis-regulatory elements (CREs), play crucial roles in regulating plant growth and development. Therefore, the combination of CRISPR/Cas technology and non-coding regulatory DNA has great potential to generate novel alleles that affect various agronomic traits of crops, thus providing valuable genetic resources for crop breeding. Herein, we review recent advances in the roles of non-coding regulatory DNA, attempts to edit non-coding regulatory DNA for crop improvement, and potential application of novel editing tools in modulating non-coding regulatory DNA. Finally, the existing problems, possible solutions, and future applications of gene editing of non-coding regulatory DNA in modern crop breeding practice are also discussed.


Element transfer by a vapor-gas stream from sulfide mine tailings: from field and laboratory evidence to thermodynamic modeling.
Condensates of vapor-gas streams were collected during field and laboratory experiments for the determination of the volatility of chemical elements in sulfide tailings under ambient conditions. The object of research was the Ursk waste heaps (Kemerovo region, Russia). Field experiments were performed on the top of the heap and in neighboring territories; the elements' concentrations in condensates from the top exceed the background values in 2-3 orders of magnitude. To obtain condensates in the laboratory, the waste material was heated to 60 °С. Laboratory condensate-contended high concentrations Ca, Mg, but Fe, Cd, Mo, Sn, Zr, and W were lower by more than 2 orders of magnitude. Also, chemical elements such as Au, Zr, Cs, U, and Tl were determined in the laboratory condensates at elevated temperatures. Also, solid samples were leached with water at the laboratory. A high positive correlation of condensate compositions with compositions of water extracts obtained from parallel samples was established. The most mobile elements transferred in the steam-gas phase are alkaline (Li, Cs, Na, K), alkaline earth (Ca, Sr), chalcophile metals (Hg, Zn, Cu), and metalloids (As, Sb, Se). The numerical experiment of metal transfer forms using thermodynamic modeling methods has been performed, including those with organic ligands.


Low-temperature bath/high-conductivity zone/stacking micellar electrokinetic chromatography for the analysis of phenolic acids in coffee drink.
Two stacking methods in micellar electrokinetic chromatography (MEKC) were investigated in this article in an attempt to increase the amount of sample injected, as well as to focus analytes onto a small zone. One employed a "high-conductivity zone", which was inserted between the sample zone and background solution to build an unequal conductivity gradient. The other employed a "low-temperature bath". A portion of the capillary was immersed in a low-temperature bath, which served as a "pseudo-low-conductivity zone". As a result, a large volume of sample injection can be achieved. Using three phenolic acids-chlorogenic acid (CGA), caffeic acid (CA) and ferulic acid (FA) in coffee as model compounds, the limit of detection (LoD) was determined to be 0.31microg/ml (S/N=3) for CGA by means of normal MEKC under suppressed electroosmotic flow (EOF). The LoD could be improved to 2.8 x10(-2), 5.3 x10(-3) and 6.0 x10(-3) microg/ml, respectively, when normal MEKC-stacking, high-conductivity zone MEKC-stacking and the low-temperature zone MEKC-stacking methods were applied. Furthermore, the high conductivity zone and the low-temperature bath were operated simultaneously on one capillary to investigate the synergism effect. The results showed that there did exist synergism effect for CGA and CA when the two were hyphenated. The stacking efficiency was higher than that of the single one used. However, there was not synergism effect for FA.


Prosthetic Valve Endocarditis After TAVR and SAVR: Insights From the PARTNER Trials.
Prosthetic valve endocarditis (PVE) is a rare but critical mechanism of valve failure and death after transcatheter and surgical aortic valve replacement (TAVR, SAVR) warranting further analysis in modern aortic valve replacement experience. We characterize the incidence, risk factors, microbiological profile and outcomes of PVE from the PARTNER trials and registries (Placement of Aortic Transcatheter Valve). We analyzed a pooled cohort of all patients in PARTNER 1 and PARTNER 2 trials and registries. Patients had severe aortic stenosis, were treated with TAVR or SAVR, and were analyzed with respect to development of PVE. PVE adjudication by a clinical events committee was based on modified Duke Criteria. The incidence, infection timing, organism, and association between PVE and all-cause mortality were analyzed. 8530 patients were included. PVE occurred in 107 cases (5.06 PVE events per 1000 person-years over a mean follow-up of 2.69±1.55 years [95% CI, 4.19-6.12]). The incidence of TAVR-PVE (5.21 PVE per 1000 person-years [95% CI, 4.26-6.38]) was not significantly different from SAVR-PVE (4.10 per 1000 person-years [95% CI, 2.33-7.22]; incident rate ratio, 1.27 [95% CI, 0.70-2.32]; P=0.44). Temporal risk of PVE was similar for TAVR and SAVR, even after adjusting for competing risk of death (hazard ratio, 1.15 [95% CI, 0.58-2.28]; P=0.69). Through multivariable analysis, PVE was associated with baseline cirrhosis (incident rate ratio, 2.86 [95% CI, 1.33-6.16]; P=0.007), pulmonary disease (incident rate ratio, 1.70 [95% CI, 1.16-2.48]; P=0.006), and renal insufficiency (incident rate ratio, 1.71 [95% CI, 1.03-2.83]; P=0.04). Timing of PVE was similar between TAVR and SAVR (<30 days: 4.2% vs 8.3%; 31 days to 1 year: 52.6% vs 66.7%; >1 year: 43.2% vs 25.0%; P=0.28). Staphylococcus occurred more commonly after SAVR (58.3% vs 28.4% in TAVR; P=0.04). PVE was strongly associated with all-cause mortality after endocarditis diagnosis (hazard ratio, 4.4 [95% CI, 3.42-5.72]; P<0.0001). The widespread adoption of TAVR and application to lower-risk patients makes understanding mechanisms of valve failure increasingly important. PVE is an established mechanism of prosthetic valve failure post-SAVR and TAVR with unclear differences between approaches. We herein demonstrate in the largest trials and registries of TAVR that PVE remains rare, but often fatal, in modern AVR experience and that there is no difference in incidence, predictors, or risk of PVE between TAVR and SAVR. https://www.clinicaltrials.gov. Unique identifiers: NCT00530894 (PARTNER 1), NCT01314313 (PARTNER 1IA), NCT02184442 (PARTNER 1IB), NCT03222141 (PII S3HR), NCT03222128 (PII S3i).


Robotic repair of iatrogenic left diaphragmatic hernia. A case report.
Iatrogenic diaphragmatic hernia after laparoscopic left adrenalectomy has been rarely reported in adults. Surgery is the preferred treatment because of the risks of incarceration, strangulation and pulmonary complications. An elderly woman with parasternal diaphragmatic hernia has been successfully treated by robotic repair with mesh placement. The short-term follow-up showed that there was no recurrence or any symptoms after the intervention. Iatrogenic diaphragmatic hernia is a rare complication occurring after abdominal or thoracic surgery. The diagnosis could be challenging because of the presence of chronic symptoms. Computed tomography can be considered the gold standard technique to assess the correct diagnosis of diaphragmatic hernias in the majority of cases. Patients with chronic symptomatic hernia should undergo surgical repair of defect. Robotic technology because of its enhanced precision and the endowrist movement of the robotic arms, facilitates the dissection near the esophago-gastric junction and the other important adjacent structures. Robotic technology seems to be a valid approach for the repair of diaphragmatic defects, even if this remains a high cost-related procedure.


Anti-androgenic effects of sewage treatment plant effluents in the prosobranch gastropod Nucella lapillus.
Recent studies performed under laboratory conditions have shown that single exposure to high levels of several xenoestrogens is able to induce imposex in at least two neogastropod species. In an attempt to evaluate if xenoestrogens, at environmentally relevant conditions, do contribute to imposex induction, we have tested the effects of a mixture containing xenoestrogens (municipal sewage effluents) on imposex development in the dogwhelk Nucella lapillus. Exposure for 3 months to the raw (0.25% and 1%) and the final sewage effluent (12.5% and 50%) rendered no increase in the severity of imposex. Conversely, as exposure to high concentrations of natural steroids, estradiol and estrone, had previously been shown to partially rescue imposex development under laboratory conditions, we have also tested if exposure to the final sewage effluent could ameliorated the severity of imposex induction by tributyltin (TBT). The results demonstrated that co-exposure to the final sewage effluent leads to a decrease trend in the severity of imposex in the presence of TBT. Within the studied imposex parameters, the Relative Penis Size index (RPSI) was the most affected with a 50% decrease in the effluent 12.5% plus TBT exposed group and 25% decrease in the effluent 50% plus TBT, if compared with the TBT alone. Overall, our results give further support to the use of imposex in N. lapillus as a specific biomarker of TBT contamination. However, in areas of high inputs of sewage effluents, the assessment of TBT contamination by the use of the imposex phenomenon should ideally also include data on the tissue levels of butyltins.


Structure, glass transition temperature and spectroscopic properties of 10Li2O-xP2O5-(89-x)TeO2-1CuO (5≤x≤25 mol%) glass system.
X-ray diffraction (XRD), field emission scanning electron microscope (FESEM), energy dispersive X-ray spectrometry (EDS), differential scanning calorimetry (DSC), infrared (IR), Raman, electron paramagnetic resonance (EPR) and optical absorption studies on 10Li2O-xP2O5-(89-x)TeO2-1CuO glasses (where x=5, 10, 15, 20 and 25 mol%) have been carried out. The amorphous nature of the glasses was confirmed using XRD and FESEM measurements. The glass transition temperature (Tg) of glass samples have been estimated from DSC traces and found that the Tg increases with increasing P2O5 content. Both the IR and Raman studies have been showed that the present glass system consists of [TeO3], [TeO4], [PO3] and [PO4] units. The spin-Hamiltonian parameters such as g∥, g⊥, and A∥ have been determined from EPR spectra and it was found that the Cu2+ ion is present in tetragonal distorted octahedral site with [Formula: see text] as the ground state. Bonding parameters and bonding symmetry of Cu2+ ions have been calculated by correlating EPR and optical data and were found to be composition dependent.


Potential confounding effects of benzyl alcohol as a formulation excipient support the elimination of the abnormal toxicity test from pharmacopoeias.
Benzyl alcohol is an excipient used in many drugs as a stabilizer. Depending on the amount present in drug formulations there might be confounding findings in the Abnormal Toxicity Test (ATT). The ATT is utilized as a quality control (QC) release test to detect extraneous contaminants according to national pharmacopoeias. Our study assessed the effects of benzyl alcohol as defined in ATT designs. This study - the first thorough evaluation of the confounding effects of benzyl alcohol on the ATT - was conducted in relation to particular health authority questions and was part of the root-cause analyses resulting from some transient behavioral findings observed in the test. Two strains of mice, CD-1 & Kunming, plus Hartley guinea pigs were administered intraperitoneally (ip), subcutaneously (sc), or intravenously (iv) with benzyl alcohol at dose level defined in the ATT design. In both mice and guinea pigs, only after ip administration, minimal behavioral changes were observed transiently within 2-3 min after administration. Therefore, the presence of benzyl alcohol in the product batch may confound the ATT results. This study provides further evidence to question the validity of the ATT for its intended use.


Potassium evoked in vivo release of substance P in rat caudate nucleus measured using a new technique of brain dialysis and an improved substance P-radioimmunoassay.
Semipermeable tubules were implanted in rat caudate nucleus in vivo. The tubules were perfused with artificial cerebrospinal fluid and the dialysates collected in fractions which were analysed for substance P content by a sensitive radioimmunoassay (detection limit: 0.1 fmol SP per sample). During controls periods no or comparatively small amounts of SP could be detected in the dialysates. An increase of the potassium concentration in the perfusion fluid to 100 mM or 200 mM induced a release of SP which tended to be concentration dependent. The present results demonstrate a new method to measure in vivo release of SP in rat brain.


A rare case report of laryngopharyngeal polyp formation following anterior cervical discectomy and fusion (ACDF).
Anterior Cervical Discectomy and Fusion (ACDF) has been regarded as the "gold standard" treatment of cervical spondylosis. Though it has good outcomes, many complications still exist, such as loss of fixation, degeneration of adjacent segments, dysphagia and pharyngeal perforation. In view of current literature, this study is the first to report a case of laryngopharyngeal polyp following ACDF. A 63 year old male patient suffered from cervical spine hyperextension after trauma accompanied by numbness of the hands and decreased muscle strength in both upper limbs. Anterior cervical fusion surgery was performed in our hospital, after which the patient's upper limb numbness disappeared and muscle strength returned to normal. In the fifth month after surgery, the patient developed a sore throat and dysphagia. Symptoms gradually worsened, and the patient was hospitalized four times, subsequently undergoing tracheotomy, internal fixation removal, and polypectomy. The patient's pronunciation, breathing, and swallowing functions returned to normal, and the incision healed. After a one-year follow-up, the polyp did not recur. Laryngopharyngeal polyp formation following ACDF has yet to be reported in literature. By excluding esophageal fistula as soon as possible, removing internal fixation and polypectomy serves as the best treatment in relieving patient symptoms.


Crystal structures of isomeric 4-bromo-N-[(2-nitro-phen-yl)sulfon-yl]benzamide and 4-bromo-N-[(4-nitro-phen-yl)sulfon-yl]benzamide.
The syntheses and crystal structures of the isomeric 4-bromo-N-[(2-nitro-phen-yl)sulfon-yl]benzamide, (I), and 4-bromo-N-[(4-nitro-phen-yl)sulfon-yl]benzamide, (II), are described (mol-ecular formula = C13H9BrN2O5S in each case). The asymmetric unit of (I) contains two independent mol-ecules [(IA) and (IB)], while that of (II) contains one mol-ecule. The benzoic acid aromatic ring of mol-ecule (IA) is disordered due to rotation about the Car-C(=O) bond over two orientations in a 0.525 (9):0.475 (9) ratio. The dihedral angle between the benzene rings is 85.9 (3)° in (IA) and 65.22 (19)° in (IB), while in (II), the corresponding value is 56.7 (7)°. In the crystals of (I) and (II), N-H⋯O, C-H⋯O and C-H⋯π inter-actions generate three-dimensional networks.


Optimal estimation of entanglement and discord in two-qubit states.
Recently, the fast development of quantum technologies led to the need for tools allowing the characterization of quantum resources. In particular, the ability to estimate non-classical aspects, e.g. entanglement and quantum discord, in two-qubit systems, is relevant to optimise the performance of quantum information processes. Here we present an experiment in which the amount of entanglement and discord are measured exploiting different estimators. Among them, some will prove to be optimal, i.e., able to reach the ultimate precision bound allowed by quantum mechanics. These estimation techniques have been tested with a specific family of states ranging from nearly pure Bell states to completely mixed states. This work represents a significant step towards the development of reliable metrological tools for quantum technologies.


iTRAQ-based comparative proteomic analysis of Vero cells infected with virulent and CV777 vaccine strain-like strains of porcine epidemic diarrhea virus.
The re-emerging porcine epidemic diarrhea virus (PEDV) variant related diarrhea has been documented in China since late 2010 and now with global distribution. Currently, a virulent PEDV CH/YNKM-8/2013 and a CV777 vaccine strain-like AH-M have been successfully isolated from the clinical samples. To dissect out the underlying pathogenic mechanism of virulent PEDV and clarify the differences between virulent and CV777 vaccine strain-like PEDV infections, we performed an iTRAQ-based comparative quantitative proteomic study of Vero cells infected with both PEDV strains. A total of 661 and 474 differentially expressed proteins were identified upon virulent and CV777 vaccine strain-like isolates infection, respectively. Ingenuity Pathway Analysis was employed to investigate the canonical pathways and functional networks involved in both PEDV infections. Comprehensive studies have revealed that the PEDV virulent strain suppressed protein synthesis of Vero cells through down-regulating mTOR as well as its downstream targets 4EBP1 and p70S6K activities, which were validated by immunoblotting. In addition, the virulent strain could activate NF-κB pathway more intensively than the CV777 vaccine strain-like isolate, and elicit stronger inflammatory cascades as well. These data might provide new insights for elucidating the specific pathogenesis of PEDV infection, and pave the way for the development of effective therapeutic strategies. Porcine epidemic diarrhea is now worldwide distributed and causing huge economic losses to swine industry. The immunomodulation and pathogenesis between PEDV and host, as well as the difference between virulent and attenuated strains of PEDV infections are still largely unknown. In this study, we presented for the first application of proteomic analysis to compare whole cellular protein alterations induced by virulent and CV777 vaccine strain-like PEDV infections, which might contribute to understand the pathogenesis of PEDV and anti-viral strategy development.


Exploring the role of physical activity and exercise for managing vascular comorbidities in people with multiple sclerosis: A scoping review.
Vascular comorbidities are prevalent among people with multiple sclerosis (MS) and have adverse disease-related consequences. In the general population, physical activity (PA) and exercise training have proven beneficial at all levels of vascular disease risk management. People with MS exhibit particularly low rates of PA; therefore, PA represents a modifiable health behavior for potentially managing vascular comorbidity risk in MS, and in turn, reducing disease burden. However, points of evidence justifying such an approach have yet to be summarized. To conduct a scoping review of existing evidence linking PA and exercise training to potential modification of vascular comorbidities and related risk factors in people with MS. We searched five electronic databases (PubMed, Ovid MEDLINE, Embase, PsycINFO, and CINAHL Plus) from inception to November 2017, for articles involving relevant vascular comorbidities (obesity, hyperlipidemia, heart disease, hypertension, and diabetes) in people with MS in conjunction with measures of PA, physical fitness, sedentary behavior, or exercise training. Studies were limited to English-language and primary research articles. Data were extracted and summarized by comorbidity type and study design (observational vs. interventional). Our initial search identified 1028 articles; subsequent screening resulted in 34 articles meeting the final inclusion criteria, including both observational (n = 17) and interventional (n = 17) studies. Most of the articles reported on obesity (n = 29), although evidence surrounding hyperlipidemia (n = 5), arterial function and hypertension (n = 5), and diabetes (n = 5) was also identified. Data supporting a beneficial role for PA or exercise training could be drawn from each comorbidity category. Overall, 14 of the 17 observational studies identified (82.4%) reported an association between higher levels of PA or cardiorespiratory fitness, or decreased sedentary behavior, and better function of at least one risk factor related to vascular comorbid conditions in people with MS. The efficacy of exercise training in limiting vascular comorbidity risk and burden was dependent upon intervention type and duration, with 9 of 17 interventional studies (52.9%) reporting improvement in at least one relevant measure of vascular comorbidity in participants with MS. Evidence points to a potential relationship between PA and exercise and risk factors related to vascular comorbidities in people with MS. PA and exercise training interventions may represent an effective therapeutic strategy for managing vascular comorbidities in people with MS, justifying further investigation.


Effects of short-term exposures to sulfuric acid and ammonium sulfate aerosols upon bronchial airway function in the donkey.
The effects of one-hour inhalation exposures to 0.3-0.6 micrometer H2SO4 and (NH4)2SO4 aerosols in the donkey were studied in terms of alterations in pulmonary flow resistance and dynamic compliance, and changes in the regional deposition and tracheobronchial mucocilliary clearance of an inert test aerosol. Short-term slowing of clearance followed certain single exposures to H2SO4 at 194-1364 microgram/m3 in three of four animals, while two of the four demonstrated a more persistent slowing of their clearance. These exposure levels produced no measurable change in resistance, compliance or regional deposition. Exposures to (NH4)SO4 up to approximately 2000 microgram/m3 had no mearurable effect upon resistance, compliance, regional deposition or mucociliary clearance.


Naphthalenebis[alpha,alpha-difluoromethylenephosphonates] as potent inhibitors of protein tyrosine phosphatases.
A series of naphthalenebis(difluoromethylenephosphonates) were prepared and compared to their monosubstituted counterparts as inhibitors of the protein phosphatases, PTP1B, CD45 and PP2A. In general, the bissubstituted compounds were better inhibitors than the mono derivatives and some of these are among the most potent, nonpeptidyl inhibitors of protein tyrosine phosphatases, PTP1B and CD45, reported to date.


Contemporary outcomes of infrapopliteal atherectomy with angioplasty versus balloon angioplasty alone for critical limb ischemia.
Limited data exist comparing atherectomy (At) with balloon angioplasty for infrapopliteal peripheral arterial disease. The objective of this study was to compare the outcomes of infrapopliteal At with angioplasty vs angioplasty alone in patients with critical limb ischemia. This is a retrospective, single-center, longitudinal study comparing patients undergoing either infrapopliteal At with angioplasty or angioplasty alone for critical limb ischemia, between January 2014 and October 2017. The primary outcome was primary patency rates. Secondary outcomes were reintervention rates, assisted primary patency, secondary patency, major adverse cardiac events, major adverse limb events, amputation-free survival, overall survival, and wound healing rates. Data were analyzed in multivariate generalized linear models with log rank tests to determine survival in Kaplan-Meier curves. There were 342 infrapopliteal interventions, 183 percutaneous balloon angioplasty (PTA; 54%), and 159 atherectomies (At) with PTA (46%) performed on 290 patients, with a mean age of 67 ± 12 years; 61% of the patients were male. The PTA and At/PTA groups had similar demographics, tissue loss (79% vs 84%; P = .26), ischemic rest pain (21% vs 16%; P = .51), mean follow-up (19 ± 9 vs 20 ± 9 months; P = .32), mean number of vessels treated (1.7 ± 0.8 vs 1.9 ± 0.8; P = .08) and the mean lesion length treated (6.55 ± 5.00 cm vs 6.02 ± 4.00 cm; P = .08), respectively. Similar 3-month (96 ± 1% vs 94 ± 1%), 6-month (85 ± 2% vs 86 ± 3%), 12-month (68 ± 3% vs 69 ± 4%), and 18-month (57 ± 4% vs 62 ± 4%) primary patency rates were seen in the two groups (P = .87). At/PTA patients had significantly higher reintervention rates as compared with the PTA patients (28% vs 16%; P = .02). Similar assisted primary patency rates (67 ± 4% vs 69 ± 4%; P = .78) and secondary patency rates (61 ± 4% vs 66 ± 4%; P = .98) were seen in the PTA and At/PTA groups at 18 months. The 30-days major adverse cardiac event rates (3% vs 2%; P = .13) and 30-day major adverse limb event rates (5% vs 4%; P = .2) were similar in both groups. Wound healing rates (72 ± 3% vs 75 ± 2%; P = .12), 1-year amputation-free survival (68 ± 4.1% vs 70 ± 2%; P = .5), and 1-year overall survival (76 ± 4% vs 78 ± 4%; P = .39) rates did not differ in the PTA and At/PTA groups. THE At/PTA group had higher local complication rates (7 [4%] vs 1 [0.5%]; P = .03) CONCLUSIONS: At with angioplasty provides similar patency rates compared with angioplasty alone for infrapopliteal peripheral arterial disease, but associated with higher reintervention and local complication rates. Further appropriately designed studies are required to determine the exact role of At in this subset of patients.


Effects of the serotonin 5-HT1B receptor agonist CP 94253 on the locomotor activity and body temperature of preweanling and adult male and female rats.
Serotonin 5-HT1A receptor agonists increase locomotor activity of both preweanling and adult rodents. The part played by the 5-HT1B receptor in locomotion is less certain, with preliminary evidence suggesting that the actions of 5-HT1B receptor agonists are not uniform across ontogeny. To more fully examine the role of 5-HT1B receptors, locomotor activity and axillary temperatures of preweanling and adult male and female rats was assessed. In the first experiment, adult (PD 70) and preweanling (PD 10 and PD 15) male and female rats were injected with the 5-HT1B agonist CP 94253 (2.5-10 mg/kg) immediately before locomotor activity testing and 60 min before axillary temperatures were recorded. In the second experiment, specificity of drug action was determined in PD 10 rats by administering saline, WAY 100635 (a 5-HT1A antagonist), or GR 127935 (a 5-HT1B antagonist) 30 min before CP 94253 (10 mg/kg) treatment. CP 94253 significantly increased the locomotor activity of preweanling rats on PD 10, an effect that was fully attenuated by GR 127935. Conversely, CP 94253 significantly decreased the locomotor activity of male and female adult rats, while CP 94253 did not affect the locomotor activity of PD 15 rats. Regardless of age, CP 94253 (2.5-10 mg/kg) significantly reduced the axillary temperatures of preweanling and adult rats. When considered together, these results show that 5-HT1B receptor stimulation activates motor circuits in PD 10 rats; whereas, 5-HT1B receptor agonism reduces the overall locomotor activity of adult rats, perhaps by blunting exploratory tendencies.


Occurrence of zearalenone in maize.
The occurrence of zearalenone in whole plants and parts of maize usually used for silage making was investigated during the cultivation period of the crop.Zearalenone was detected upto several hundreds of μg/kg DM, that mainly accumulated at the end of the ripening process thus contaminating the silages subsequently. The highest concentrations of zearalenone were observed in the leaves especially at the bottom of the plant, which may correlate with leaf necrosis increasing towards harvest. Further research is needed to clarify health risks for farm animals due to uptake of contaminated feed and possible carry-over of zearalenone and its metabolites into the food chain of man.


An alcohol dehydrogenase ribozyme.
We report an RNA molecule that exhibits activity analogous to that of alcohol dehydrogenase (ADH). Directed in vitro evolution was used to enrich nicotinamide adenine dinucleotide (NAD+)-dependent redox-active RNAs from a combinatorial pool. The most active ribozyme in the population forms a compact pseudoknotted structure and oxidizes an alcohol seven orders of magnitude faster than the estimated spontaneous rate. Moreover, this ADH RNA was coupled with a redox relay between NADH and flavin adenine dinucleotide to give a NAD+-regeneration system. Our demonstration of the redox ability of RNA adds support to an RNA-based metabolic system in ancient life.


Does climate affect host-plant quality? Annual variation in the quality of balsam fir as food for spruce budworm.
The hypothesis that annual climatic variation can affect the nutritive value of host-plant tissue for a herbivore was tested. Larvae of a single generation of western spruce budworm, Choristoneura occidentalis Free., were fed foliages that had been collected on five consecutive springs from a stand of balsam fir Abies balsamea (L.) Mill. Budworm of both sexes were about 20 percent heavier at pupation when fed folages that had been produced in early rather than later spring seasons. This could result in an estimated 25 percent difference in the reproductive rate of females. It is concluded that annual variations in spring climate can affect the nutritive value of forage.


Modulation of antibody binding affinity by somatic mutation.
The affinity of hapten binding of monoclonal antibodies (MAbs) specific for 4-hydroxy-3-nitrophenylacetyl (NP) has been investigated at the molecular level by both site-specific mutagenesis and recombinant antibody construction, followed by expression in myeloma cells. We have shown that a single point mutation (trp----leu at codon 33) in the variable region of the heavy chain (VH) is sufficient to endow a primary-response, germline-encoded antibody with an affinity for antigen typical of a secondary-response antibody carrying the same mutation. We have also demonstrated that mutations additional to the trp----leu exchange in the heavy chain and further mutations in the light chain are irrelevant to the high-affinity phenotype of secondary-response antibodies. Since some of these are "parallel" mutations common to clonally unrelated antibodies, this suggests that the mutation rate is not constant across the entire immunoglobulin variable region. Although antibodies with a trp----leu exchange at position 33 are positively selected because of improved hapten binding affinity, we have found that, under rare circumstances, other patterns of mutations may be selected through particular D-JH combinations; we have demonstrated one case where this has generated an antibody with very efficient hapten binding ability.


Morphogenesis and pathogenesis of chronic lung diseases. XX. Effects of repeated hypersensitivity reactions upon experimental immuno-granulomas of the lung.
In order to analyse the effects of repeated hypersensitivity reactions upon chronic lung lesions, lung granulomas were experimentally induced in rabbits by an intravenous injection of 1 ml of the complete Freund's adjuvant added with 10 per cent human gammaglobulin. Groups of rabbits with 14- and 21-day-granulomas were intratracheally challenged with 1.000 I.U. human gammaglobulin injected two or three times at 7-9 days interval. The responses of the lung tissue were of the Arthus type with neutrophil granulocytic accumulations and proteasic action; the intensity of cell accumulations was decreasing after the 2nd and 3rd challenge. The lesional evolution after challenge showed intra- and perigranulomatous infiltrations with alkaline-phosphatase positive lymphocytes and plasma cells. The density of the intragranulomatous reticulin network developed after the hypersensitivity reactions increased progressively and was morphometrically assessed as statistically significant. Cellular and fibrillar lesions led to the restructuring of the lung tissue.


Effect of aging on the kinetic characteristics of the insulin receptor autophosphorylation in rat adipocytes.
The effect of aging on the insulin binding parameters and on the kinetic characteristics of the insulin receptor autophosphorylation in rat adipose tissue has been investigated. Using solubilized receptors from adipocyte plasma membranes, no significant differences were identified in either affinity or receptor number in adult vs old rats. Time courses for in vitro receptor phosphorylation revealed that both the initial rate of autophosphorylation and the maximal 32P incorporation were decreased by 40% in old (24-month) animals as compared to adult (3-month) control rats. The tyrosine phosphatase activity associated with the adipocyte plasma membranes does not account for the decreased kinase activity found in old rats. Insulin sensitivity (measured as the dose of insulin required for 50% maximal stimulation of kinase activity) was similar in both groups of rats. However, the kinase activity showed a decreased responsiveness to the hormone in the old rats. Double reciprocal plot analysis of receptor phosphorylation revealed that the Km for ATP was not modified. In contrast, the insulin-stimulated Vmax value was decreased by two-fold in 24-month-old rats. The decrease in Vmax does not appear to be related to an increased basal phosphorylation level on Ser/Thr residues of the C terminus of the receptor beta-subunit. Thus, we conclude that the reduced insulin receptor kinase activity in adipose tissue from old rats is due, at least in part, to a defect of the intrinsic kinase activity of the insulin receptor.


Intraarterial management of giant-cell tumors of the spine in children.
Transcatheter arterial management of giant cell tumors of the spine was performed in two female patients aged 12 and 15 who had failed to respond to conventional therapy. Response was determined clinically by alleviation of pain and radiographically by regression and/or calcification of the tumor. Minor side effects included transient nausea, elevated body temperature, and pain.


Tuberculous myositis and cellulitis in a renal transplant recipient.
Tuberculosis, a disease known as White plague, caused by Mycobacterium tuberculosis, is known for its diverse manifestations. The atypical manifestations of tuberculosis pose a great diagnostic challenge to the clinicians. Though low oxygen and high lactic acid content in skeletal muscle makes it an unfavourable site for the survival of these aerobic bacilli, they still can infect muscles and present as myositis. Tuberculous myositis and cellulitis are such a rare entity, that they are never considered as a possible differential diagnosis even in tuberculosis endemic countries. In this case report, we share our experience with a renal transplant recipient who presented to us with right lower limb pain and swelling.


Is expertise in pediatric surgery necessary to perform laparoscopic splenectomy in children? An experience from a department of general surgery.
Splenectomy is frequently required in children for various hematologic pathologic findings. Because of progress in minimally invasive techniques, laparoscopic splenectomy (LS) has become feasible. The objective of this report is to present a monocentric experience and to evaluate the efficacy of and complications observed after laparoscopic splenic procedures in a department of general surgery. 57 consecutive LSs have been performed in a pediatric population between January 2000 and October 2010. There were 33 females and 24 males with a median age of 12 years (range 4-17). Indications were: hereditary spherocytosis 38 cases, idiopathic thrombocytopenic purpura 10, sickle cell disease (SCD) 6, thrombocytopenic thrombotic purpura 2 and non-hodgkin lymphoma 1 case. Patients were operated on using right semilateral position, employing Atlas Ligasure vessel sealing system in 49 cases (86%) and Harmonic Scalpel + EndoGIA in 8. In 24 patients (42.1%), a cholecystectomy was associated. Two patients required conversion to open splenectomy (3.5%). In three cases, a minilaparotomy was performed for spleen removal (5.2%). Accessory spleens were identified in three patients (5.2%). Complications (8.8%) included bleeding (two), abdominal collection (one) and pleural effusion (two). There was no mortality. Average operative time was 128 min (range 80-220). Average length of stay was 3 days (range 2-7). Mean blood loss was 80 ml (range 30-500) with a transfusion rate of 1.7% (one patient). Laparoscopic spleen surgery is safe, reliable and effective in the pediatric population with hematologic disorders and is associated with minimal morbidity, zero mortality, and a short length of stay. Ligasure vessel sealing system shortened operative time and blood loss. On the basis of the results, we consider laparoscopic approach the gold standard for the treatment of these patients even in a department of general surgery.


Cerebral 18 F-fluorodeoxyglucose metabolism alteration of reward- and motivation-related regions in groups of different BMI classifications.
This study explored the relationship between BMI and regional cerebral glucose metabolism and explicitly detected regions with significant differences in cerebral metabolism using positron emission tomography (PET)/magnetic resonance imaging in the resting state. Corresponding PET images acquired from 220 participants were sorted into four groups according to Asian BMI standards: underweight, normal weight, overweight, and obesity. Pearson correlation coefficient analysis was performed to assess the association between BMI and standard uptake value. The regional cerebral glucose metabolism was measured in the fasted state. The PET images were analyzed using statistical parameter maps. One-way ANOVA was used to explore differences in the standard uptake value as an indicator of regional cerebral glucose metabolism. This study found that lower cerebral glucose metabolism in reward- and motivation-related regions was accompanied by more severe obesity and that regional cerebral glucose metabolism activities were negatively correlated with BMI. In addition, more severe obesity was accompanied by a larger range of areas with significant differences independent of current dietary status. These findings suggest that the reward and motivation circuits may be a factor regulating energy balance and influencing the degree of obesity.


An analysis of the outcome of 301 malignant colorectal tumors.
The results of surgical treatment of 301 patients with malignant tumors of the colon and rectum presenting to two small district general hospitals in the years 1972 to 1977 were analyzed. Two hundred seventy-four patients (91 per cent) underwent surgery with an operative mortality of 8.7 per cent. Curative resections were performed in 58 per cent of the patients. The overall crude five-year survival rate was 32 per cent. The crude five-year survival rates for curative resection, palliative procedures, and inoperable patients were 47 per cent, 11 per cent, and 0 per cent, respectively. Survival rates were considerably improved in patients in the 40-to-50-year age group with 9 to 12 months' duration of symptoms, and in those with early unfixed, resected tumors. It was diminished in patients with bowel perforation presenting as an emergency, and in patients with two weeks or less duration of symptoms. Survival was not related to the site or grade of the tumor.


[Correlation between the level of fluorescent aging pigments in homogenates of the rat cerebral cortex and the constant brain potential during late ontogenesis].
A strong correlation (R = 0.5 + 0.88) was found between the constant potential level of the rat brain and the content of aging pigments in the brain cortex homogenates. The latter was measured by synchronous scanning of luminescence in each hemisphere separately.


Integrating Basic Science into Endocrine Clinical Electives.
Practical and effective methods to integrate basic science material into clinical electives are lacking. We developed a primer for medical students participating in an ambulatory endocrinology elective highlighting pathophysiology, symptoms, diagnosis, and management of disorders. Students felt better prepared for the elective and mean scores on the endocrine knowledge test improved (7.5 (SD = 2.4) to 9.6 (SD = 2.2), p < 0.001). The endocrine primer required minimal faculty time and resources while integrating basic science information into a clinical elective, standardizing students' knowledge, and enhancing student satisfaction with the elective. This innovative primer lays the groundwork to expand to other specialty electives and institutions.


Heterogeneity in wheat germ agglutinin binding by mouse peritoneal macrophages.
The binding of the lectin wheat germ agglutinin (WGA) to the cell surface of monocytes and macrophages obtained from the stimulated peritoneal cavity of mice was investigated electron microscopically, using ovomucoid-gold as an indirect marker. Resident (tissue) macrophages, identified by the presence of PO activity in the rough endoplasmic reticulum as well as in the nuclear envelope, showed low WGA binding, whereas monocytes and monocyte-derived macrophages with PO activity in the granules showed high WGA binding. Since cells devoid of PO activity showed variable WGA binding, the value of this gold-WGA-binding technique for discrimination on a quantitative basis between resident macrophages and monocytes or monocyte-derived macrophages, is discussed.


VIL-A1, a monoclonal antibody reactive with common acute lymphatic leukemia cells.
The VIL-A1 monoclonal antibody raised against Reh cells reacts with common acute lymphatic leukemia (CALL) cells but not with normal or malignant B or T lymphocytes. It also shows no binding to normal or malignant myeloid, monocytic or erythroid cells, nor does it react with thrombocytes. The antibody is of IgM class and lyses CALL cells very efficiently in the presence of rabbit but not human complement. Immunoprecipitation experiments followed by SDS-polyacrylamide gel electrophoresis under reducing conditions revealed that VIL-A1 defines a 95,000 mol. wt membrane protein. Approximately 40% of it binds to lens culinaris lectin. Capping experiments showed that the membrane component defined by VIL-A1 co-caps with the one recognized by another recently described monoclonal antibody to CALL cells (J5).


Historical vignette: a life with poxviruses and publishers.
Although I started science investigating the physical anthropology of Australian aboriginals and then spent six years in the Australian Army during the 1939-45 war, largely working on malaria control, the poxviruses have been the focal point of my research--at the bench, in the field, on committees, and in front of my word processor. I have had a relatively short period as a scientist at the bench, just over twenty years out of the sixty years since I graduated. For the last thirty years the pipette has been replaced by the pen and the word processor, and contacts with publishers have become an important element in my life. My pilgrim's progress, from mousepox through myxomatosis to vaccinia and then smallpox, has been helped by what can only be described as good luck, coming in many guises. I have been fortunate in many ways; in my father and mother and the genes and family life they gave me; in my wife, who was an immense source of support until her death in 1995; in the people whom I met during the Second World War; and in my close association with three great scientists, Macfarlane Burnet, René Dubos, and Howard Florey. I had the good fortune to be appointed, as a young and inexperienced virologist, to one of the best research jobs in the world, as a professor in the Australian National University. I have been very lucky in having had the opportunity to exploit a series of scientific gold mines; in turn, malaria, during the War, then mousepox, an unexploited virus because its use was forbidden in the United States, then, after a brief flirtation with mycobacteria, myxomatosis, an unparalleled natural experiment of evolution in action, and finally the most impressive achievement in public health in world history, the global eradication of smallpox. My last job in the University before retirement provided me with the opportunity to do something about the most important problems confronting humankind: the degradation of the environment, driven by the explosion in human numbers and their ever-growing use of resources. Each of these activities has provided opportunities to establish and maintain close friendships with scientists all over the world.


Male contraception development: monitoring effective spermatogenesis suppression utilizing a user-controlled sperm concentration test compared with standard semen analysis.
To determine whether a user-controlled sperm concentration test compared with standard semen analysis can effectively monitor spermatogenesis suppression for male contraception. Single center, prospective sub study of the ongoing clinical trial: "Study of daily application of Nestorone and testosterone combination gel for male contraception." Research institute at an academic medical center. Couples participating in the male contraceptive clinical trial. None. The ability by participants to monitor sperm suppression to a threshold compatible with contraceptive efficacy utilizing a user-controlled test verified by sperm concentration determined by standard laboratory methods. Thirty-eight men participating in a hormonal male contraceptive clinical trial provided multiple samples during spermatogenesis suppression for this substudy. Participants, employing a user-controlled test, correctly identified the absence of sperm (a negative test) in 100% of their laboratory-confirmed azoospermic samples (n = 122). Participants also identified 100% of samples (n = 73) with sperm >0.2 million/mL as positive. Sperm counts between 0.01 and 0.2 million/mL were identified as negative in 96% of samples. Trial participants noted the overall ease of using the test with respect to sample preparation, test timing, and result interpretation, and that they could accurately use this test at home without difficulty. Participants undergoing spermatogenesis suppression in a hormonal male contraceptive trial performed user-controlled test to determine whether their semen sperm concentration was ≤ or >0.2 million/mL. Compared with standard semen analyses, participants correctly identified 100% of samples with sperm counts >0.2 million/mL as positive (Sensitivity 100%). A positive result when the couple is using a male contraceptive method triggers the need for semen analysis by a laboratory while the couple uses another method of contraception. Participants correctly diagnosed samples ≤0.2 million sperm/mL as negative in 99% of samples (specificity 99%). A negative result indicates a sperm concentration ≤0.2 million/mL, well below the threshold of ≤1 million/mL offering contraceptive efficacy demonstrated by prior studies. At-home sperm concentration test would minimize the need for users to return to the clinic to monitor suppression of spermatogenesis, decreasing cost and burden of male contraception trials and increasing practicality of the method. NCT: 03452111.


Hand-foot syndrome associated with short infusions of combination chemotherapy with gemcitabine and vinorelbine.
The hand-foot syndrome (palmar-plantar erythrodysesthesia) is a side-effect which is associated with several cytotoxic agents (e.g. 5-fluorouracil, UFT, capecitabine, cytarabine, doxorubicin, liposomal-encapsulated doxorubicin). An association with a prolonged infusion of high doses of vinorelbine has also been described. To date a hand-foot syndrome after gemcitabine or short infusions of vinorelbine has not been reported before. The patient described here had a non-small-cell lung cancer stage IIIB disease and developed a hand-foot syndrome after short infusions of standard-dose chemotherapy of a combination with gemcitabine and vinorelbine.


Mutagenicity of chromium picolinate and its components in Salmonella typhimurium and L5178Y mouse lymphoma cells.
Chromium picolinate is one of the most commonly used chromium dietary supplements available in the United States, and it has been marketed to consumers for use in weight loss, increasing muscle mass, and lowering serum cholesterol. Chromium picolinate is a synthetic compound that provides a bioavailable form of Cr(III) that is absorbed better than dietary chromium. However, there are several reports that it can have adverse effects. In order to study the mechanism of observed cellular toxicity and mutagenicity, chromium picolinate and its component compounds, chromium (III) chloride and picolinic acid, were evaluated in Salmonella typhimurium and L5178Y mouse lymphoma cells. Neither chromium picolinate nor chromium chloride induced a mutagenic response in S. typhimurium. However, in the L5178Y mouse lymphoma mutation assay, chromium picolinate induced mutagenic responses without and with the addition of S9.


Design of doxorubicin encapsulated pH-/thermo-responsive and cationic shell-crosslinked magnetic drug delivery system.
The upsurge in cancer cases, such as liver cancer, has claimed millions of lives globally and has prompted the development of novel nanodrug delivery systems. These systems allow cancer drugs to be encapsulated in nanocarriers and delivered to tumor sites, and accordingly, help reduce side effects of the current chemotherapeutic treatments. Herein, we prepared nanocarriers comprising magnetic iron oxide (MIO) nanoparticles that were surface modified with crosslinked Pluronic F127 (PF127) and branched polyethylenimine (bPEI) to form MIOpoly nanocarriers. These nanocarriers were then loaded with doxorubicin (DOX) anticancer drug to form the MIOpoly-DOX complex. The nanocarriers were magnetite and possessed superparamagnetic properties. Small-angle neutron scattering (SANS) analysis indicated that the nanocarriers were thermoresponsive and spherically structured. The characteristic peaks at 1285, 1619, 2844, 2919, 2900, 2840, and 3426 cm-1, corresponding to those of CN, -NH2, -CH2, and OH-, confirmed the successful crosslinking, coating of PF127-bPEI polymers on the surface of MIO nanoparticles and DOX conjugation. The bioavailability of the nanocarriers indicated a more than 85% cell viability when using HepG2 liver cancer cells. A pH (54.8% release in 48 h; pH = 5.4) and temperature (51.0% release in 48 h; 42 °C)-dependent release of DOX was observed, displaying a Korsmeyer-Peppas kinetics model at low pH and Weibull model at high temperatures. The high DOX fluorescence observed for MIOpoly-DOX indicated a high cellular uptake enhanced by alternating magnetic field. These results suggest that MIOpoly synthesized using a combined approach of surface crosslinking and grafted with PF127-bPEI appear to offer promising properties as drug delivery system. Therefore, the nanocarriers developed in the study possess a great potential for targeted delivery and thereby circumventing the limitations of conventional chemotherapy.


Association of Acute, High-dose Cadmium Exposure with Alterations in Vascular Endothelial Barrier Antigen Expression and Astrocyte Morphology in the Developing Rat Central Nervous System.
Clinical and experimental studies have demonstrated the neurotoxic and behavioural effects of cadmium. However, the exact pathophysiological mechanism(s) of cadmium neurotoxicity on the human central nervous system (CNS) is not completely understood. A rat blood-brain barrier (BBB) endothelial marker, the endothelial barrier antigen (EBA), has been identified and we have shown previously that an anti-EBA IgG1 antibody exclusively recognizes barrier-competent microvessels in the rat CNS and peripheral nervous system (PNS). Endothelial cells of peripheral tissues or brain regions possessing fenestrated microvascular endothelia do not display immunoreactivity for EBA. Here, we describe the application of sequential indirect immunofluorescence with anti-EBA, and an antibody directed against glial fibrillary acidic protein (GFAP), to evaluate the immunoreactivity patterns and morphological alterations in BBB microvessels and astrocytes, following a single, high dose of cadmium in normal, term-delivered young rats. We detected a moderate reduction in immunoreactivity and number of microvessels labelled by the anti-EBA in the forebrain, cerebellum and midbrain in cadmium-exposed rats compared with normal controls. We observed weakly GFAP-reactive astrocytes displaying cell bodies with ill-defined borders and blurred cytoplasm within the white and grey matter of cadmium-exposed brains. The astrocyte nuclei were markedly enlarged, intensely hyperchromatic and exhibited chromatin condensation with nuclear fragmentation. This study indicates for the first time that EBA is involved in, and could serve as a potentially useful marker for studying, cadmium neurotoxicity in the rat model system.


Associations of Uncertainty With Psychological Health and Quality of Life in Older Adults With Advanced Cancer.
Older adults with advanced cancer face uncertainty related to their disease and treatment. To evaluate the associations of uncertainty with psychological health and quality of life (QoL) in older adults with advanced cancer. Secondary cross-sectional analysis of baseline data from a national clustered geriatric assessment trial. Patients 70 years and older with advanced cancer considering a new line of chemotherapy were recruited. We measured uncertainty using the modified nine-item Mishel Uncertainty in Illness Scale. Dependent variables included anxiety (Generalized Anxiety Disorder-7), depression (Generalized Depression Scale-15), distress (distress thermometer), QoL (Functional Assessment of Cancer Therapy-General), and emotional well-being (Functional Assessment of Cancer Therapy-General subscale). We used multivariate linear regression analyses to evaluate the association of uncertainty with each dependent variable. We conducted a partial least squares analysis with a variable importance in projection (VIP) plot to assess the contribution of individual variables to the model. Variables with a VIP <0.8 were considered less influential. We included 527 patients (median age 76 years; range 70-96). In multivariate analyses, higher levels of uncertainty were significantly associated with greater anxiety (β = 0.11; SE = 0.04), depression (β = 0.09; SE = 0.02), distress (β = 0.12; SE = 0.02), as well as lower QoL (β = -1.08; SE = 0.11) and emotional well-being (β = -0.29; SE = 0.03); the effect sizes were considered small. Uncertainty items related to disease and treatment were most strongly associated with psychological health and QoL scores (all VIP >0.8). Uncertainty among older patients with advanced cancer is associated with worse psychological health and QoL. Tailored uncertainty management strategies are warranted.


Risk stratification with vasodilator stress SPECT myocardial perfusion imaging in patients with elevated cardiac biomarkers.
Although the diagnostic accuracy and prognostic utility of vasodilator stress MPI have been well established in the non-acute setting, the efficacy of all of the vasodilator stressors in risk stratifying post-MI patients as well as the evaluation of cardiac troponin elevation of unclear etiology is not established. Accordingly, the aim of the present study was to investigate the prognostic efficacy of vasodilator stress MPI in the setting of elevated cardiac troponin to accurately risk stratify these higher-risk patients. All patients from two tertiary centers, from 1/1/2010 through 12/31/2012, with elevated cardiac biomarkers within < 7 days and undergoing stress SPECT MPI testing were studied. Results of stress MPI were scored using a 17-segment model based on semiquantitative scoring as normal or abnormal (mild, moderate, or severe) using a total perfusion defect (TPD) of 0%, 1-10%, 10-20%, and > 20%. Mortality data through the year 2014 were obtained from the National Death Index, and survival analyses were performed. The primary endpoint was all-cause mortality with the secondary endpoint being cardiac mortality. A total of 503 patients were followed for an average of 33.6 ± 16.2 months, with a mean age of 69.3 years; 53.7% male; and a majority (88.7%) of them undergoing vasodilator stress. A significant increase in all-cause mortality was seen based on the severity of TPD results for all vasodilators (P < .0001) and regadenoson (P < .0001). Similar prognostic ability was seen for all-cause mortality. This association was maintained even after adjustment for cardiac risk factors, previous coronary disease, and troponin quartiles. MPI results (stress TPD and LVEF) added to traditional cardiac risk factors, and troponin values resulted in a significant incremental increase in the ability to predict all-cause and cardiac mortality, and stress TPD remained independently predictive for both all-cause and cardiac mortality in a multivariate model. Vasodilator stress (including regadenoson) MPI effectively risk stratifies patients with recently elevated cardiac biomarkers, with the increasing risk of mortality with the increasing severity of perfusion defects. It provides incremental prognostic value, in addition to clinical factors and degree of troponin elevation.


Oral health status of older people living in care homes in Wales.
UK adult dental health surveys (ADHS) exclude care home residents from sampling. Aim To understand oral health status of care home residents in Wales using ADHS criteria. Cross sectional survey of care home residents in Wales using a questionnaire and oral examination contemporaneous with, and paralleling, the ADHS 2009. 708 randomly selected participants from 213 randomly selected care homes participated including individuals with and without capacity. 72.8% of residents had tooth decay. Compared to older adults examined in the ADHS, residents are less likely to brush teeth/dentures twice a day (37% vs 63%), more likely to only attend a dentist when they have a problem (63% vs 26%), have more teeth with active decay (3.1 vs 0.9), more have current dental pain (13% vs 5%) and other morbidity (open pulp, ulceration, fistulae, abscess 27% vs 10%). High decay is present in both recently admitted and longer term residents. There was some regional variation in levels of oral hygiene. Oral health status of older people resident in care homes in Wales is poor. Findings suggest more could be done to improve preventive care both before and after admission to the care home.


Correlating Thermodynamics with Cognitive Outcomes in Magnetic Resonance-guided Laser Interstitial Thermal Therapy (MRgLITT) of a Pediatric Hypothalamic Hamartoma.
Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) is a commonly used clinical method of destroying intracranial brain foci. Our objective was to correlate the thermal damage estimate transition zone with cognitive outcomes in MRgLITT of a pediatric hypothalamic hamartoma. Uncomplicated MRgLITT was used to disconnect an 8-mm left Delalande grade II hypothalamic hamartoma (HH) revealed on neuroimaging of a 17-year-old male patient with drug-resistant epilepsy and a "gelastic +" semiology including both gelastic and tonic-clonic seizures. Despite meticulous planning, submillimetric stereotactic accuracy, and reassuring intraoperative thermography, the patient experienced transient, but profound, global amnesia. Retroactively, we applied a new iteration of thermographic software that overlays a magenta-colored transition zone (TZ) around the necrotic zone defined by the orange-pigmented thermal damage estimate (TDE). Clear involvement of the bilateral mesial circuits was demonstrated by the overlay of the TZ on the TDE. Involvement of the bilateral mesial circuits visualized with TDE and TZ could account for the neurocognitive outcomes of our patient. We highlight this case as our understanding of thermography analysis evolves, emphasizing principles of technique and trajectory planning, as well as considerations during thermablation to help inform surgical decision-making.


Motor effects of acute and chronic inhibition of nitric oxide synthesis in mice.
Systemic injections of nitric oxide synthase (NOS) inhibitors have been shown to decrease exploratory behavior in rats. This effect may be related to motor impairments since these drugs can induce catalepsy in rodents. To compare the effects of two NOS inhibitors in tests aimed to investigate exploratory behavior and to assess motor control. The acute effects of the NOS inhibitors NG-nitro- L-arginine ( L-NOARG, 10-80 mg/kg IP) and 7-nitroindazole (7-NIO, 3-30 mg/kg IP) on exploratory activity were analyzed in an open field arena. Drug effects on catalepsy were examined in the hanging-bar and wire-ring test. Footprint pattern after treatment with the two NOS inhibitors was evaluated and the results compared with those obtained with the dopamine D2 receptor antagonist haloperidol (1-2 mg/kg IP). Sub-chronic (twice a day for 4 days) effects of L-NOARG (40 mg/kg) or 7-NIO (30 mg/kg) were also tested in the open field arena and catalepsy test. L-NOARG and 7-NIO decreased locomotion and rearing in the open field arena. Both drugs induced catalepsy in the hanging-bar test but did not change footprint pattern. The cataleptic effect of L-NOARG in the hanging bar and wire-ring tests were highly correlated ( r=0.927). The exploratory and cataleptic effects of L-NOARG and 7-NIO provided evidence for tolerance after sub-chronic treatment. These results confirm that inhibition of neuronal NO formation induces impairment of exploratory behavior. This effect does not seem to involve aspects evaluated by footprint analysis, such as weight support, trunk stability and foot placement. They could, however, be related to drug-induced catalepsy.


A highly selective sensor based on p-tetranitrocalix[4]arene-capped copper nanoparticles for colorimetric and bare-eye detection of cyclophosphamide.
In the current study, one of the outstanding facile and simple protocols is proposed for the synthesis of copper nanoparticles (CuNPs) using NaBH4 as a reducing agent and p-tetranitrocalix[4]arene (p-TNC4) as a capping agent. According to our knowledge, no such technique is available in the literature for colorimetric detection of cyclophosphamide (CPA) using CuNPs at the trace level. The well-organized synthesis was confirmed via advanced spectroscopic techniques. The crystallite size, shape, phase purity, and morphological characteristics were determined via XRD, AFM, FT-IR, and UV-visible spectroscopy. At the optimal conditions for CPA detection, the sensor reveals an excellent sensitivity, selectivity, as well as stability with LOD and LOQ 20 nM and 60 nM, respectively. However, the proposed sensor showed excellent potential and selectivity for the sensing of colorimetric detection of CPA that can be effectively applied to real blood serum samples. The proposed approach is better suited as compared to reported protocols in terms of handling, simplicity, economic, energy consumption, reproducibility, and excellent performance in a very short time.


Comparison of in vitro BBMEC permeability and in vivo CNS uptake by microdialysis sampling.
The studies presented in this report were designed to assess the correlation of the bovine brain microvessel endothelial cell (BBMEC) apparent permeability coefficient (P(app)) and in vivo BBB penetration using microdialysis sampling. A mathematical model was developed to describe the relationship of brain extracellular fluid (ECF) concentration to free drug in plasma. The compounds studied have a broad range of physico-chemical characteristics and have widely varying in vitro and in vivo permeability across the blood-brain barrier (BBB). BBMEC permeability coefficients vary in magnitude from a low of 0.9 x 10(-5) cm/s to a high value of 7.5 x 10(-5) cm/s. Corresponding in vivo measurements of BBB permeability are represented by clearance (CL(in)) into the brain ECF and range from a low of 0.023 microl/min/g to a high of 12.9 microl/min/g. While it is apparent that in vitro data from the BBMEC model can be predictive of the in vivo permeability of a compound across the BBB, there are numerous factors both prior to and following entry into the brain which impact the ultimate uptake of a compound. Even in the presence of high BBB permeability, factors such as high plasma protein binding, active efflux across the BBB, and metabolism within the CNS can greatly limit the ultimate concentrations achieved. In addition, concentrations in the intracellular space may not be the same as concentrations in the extracellular space. While these data show that the BBMEC permeability is predictive of the in vivo BBB permeability, the complexity of the living system makes prediction of brain concentrations difficult, based solely on the in vitro measurement.


The relationship between infection and disease in Wuchereria bancrofti infection in Ghana.
The relationship between infection and clinical disease in Wuchereria bancrofti infection was investigated in a community-based study in different endemic areas in Ghana. At the individual level, there was no association between acute adenolymphangitis and infection (microfilaraemia) status. There was a negative association between infection status and lymphoedema/elephantiasis, but a positive association with hydrocele; however, the intensity of infection was negatively associated with both elephantiasis and hydrocele. The community prevalence of infection was strongly associated with the prevalence of clinical filariasis (especially hydrocele). There was a strong positive association between the prevalence of infection in males and the odds of a case of hydrocele being microfilaraemic, suggesting that there is no acquired immunity to reinfection in cases of hydrocele. The pathophysiologies of elephantiasis and hydrocele may therefore differ from one another, and require further investigation.