Vibration-guided mate searching in treehoppers: directional accuracy and sampling strategies in a complex sensory environment.
Animal movement decisions involve an action-perception cycle in which sensory flow influences motor output. Key aspects of the action-perception cycle involved in movement decisions can be identified by integrating path information with measurement of environmental cues. We studied mate searching in insects for which the primary sensory cues are mechanical vibrations traveling through the tissues of living plants. We mapped search paths of male thornbug treehoppers locating stationary females through an exchange of vibrational signals. At each of the males' sampling locations, we used two-dimensional laser vibrometry to measure stem motion produced by female vibrational signals. We related properties of the vibrational signals to the males' movement direction, inter-sample distance and accuracy. Males experienced gradients in signal amplitude and in the whirling motion of the plant stem, and these gradients were influenced to varying degrees by source distance and local stem properties. Males changed their sampling behavior during the search, making longer inter-sample movements farther from the source, where uncertainty is higher. The primary directional cue used by searching males was the direction of wave propagation, and males made more accurate decisions when signal amplitude was higher, when time delays were longer between the front and back legs, and when female responses were short in duration. The whirling motion of plant stems, including both the eccentricity and the major axes of motion, is a fundamental feature of vibrational environments on living plants, and we show for the first time that it has important influences on the decisions of vibrationally homing insects.


Brachypodium distachyon BdPP2CA6 Interacts with BdPYLs and BdSnRK2 and Positively Regulates Salt Tolerance in Transgenic Arabidopsis.
The phytohormone abscisic acid (ABA) is essential in plant responding to biotic and abiotic stresses. Although ABA signaling model is well established in Arabidopsis, ABA receptor PYL family and clade A PP2C subfamily are not yet characterized in monocot model plant Brachypodium distachyon. In this study, we identified 12 PYLs and 8 clade A PP2Cs from B. distachyon genome and successfully cloned 12 PYLs and 7 clade A PP2Cs. Bioinformatic and expression analyses showed that most of the identified genes respond to several signal molecules and abiotic stresses. Protein-protein interaction analysis revealed that many BdPYLs and BdPP2CAs participate in the classic ABA-PYL-PP2C-SnRK2 signaling pathway. A clade A PP2C, designated BdPP2CA6, interacted with BdPYL11 in the absence of ABA and localized in nucleus. Most clade A PP2C members from Arabidopsis showed negatively regulation in ABA signaling pathway, whereas BdPP2CA6-overexpression transgenic Arabidopsis showed ABA hypersensitive phenotype, resulting in enhanced stomatal closure and salinity tolerance. Our results indicate that BdPP2CA6 positively regulates ABA and stress signal pathway in transgenic Arabidopsis plant seedlings.


The Arabidopsis R2R3 MYB proteins FOUR LIPS and MYB88 restrict divisions late in the stomatal cell lineage.
The two guard cells of a stoma are produced by a single symmetric division just before terminal differentiation. Recessive mutations in the FOUR LIPS (FLP) gene abnormally induce at least four guard cells in contact with one another. These pattern defects result from a persistence of precursor cell identity that leads to extra symmetric divisions at the end of the cell lineage. FLP is likely to be required for the correct timing of the transition from cell cycling to terminal differentiation. FLP encodes a two-repeat (R2R3) MYB protein whose expression accumulates just before the symmetric division. A paralogous gene, MYB88, overlaps with FLP function in generating normal stomatal patterning. Plants homozygous for mutations in both genes exhibit more severe defects than flp alone, and transformation of flp plants with a genomic MYB88 construct restores a wild-type phenotype. Both genes compose a distinct and relatively basal clade of atypical R2R3 MYB proteins that possess an unusual pattern of amino acid substitutions in their putative DNA binding domains. Our results suggest that two related transcription factors jointly restrict divisions late in the Arabidopsis thaliana stomatal cell lineage.


Nephrotic syndrome associated with use of the nonsteroidal anti-inflammatory drugs. Case report and review of the literature.
Although acute interstitial nephritis associated with the use of nonsteroidal anti-inflammatory drugs has long been recognized, only recently has its association with 'minimal change' nephrotic syndrome been reported. We report here a case of this pattern of nephrotic syndrome without concurrent interstitial nephritis associated with the use of tolmetin. The clinical picture, laboratory data, course, and relevant histopathologic findings of previous cases in the literature of nephrotic syndrome related to the use of the nonsteroidal anti-inflammatory drugs are reviewed and discussed.


Insights Into the Resistome of Bovine Clinical Mastitis Microbiome, a Key Factor in Disease Complication.
Bovine clinical mastitis (CM) is one of the most prevalent diseases caused by a wide range of resident microbes. The emergence of antimicrobial resistance in CM bacteria is well-known, however, the genomic resistance composition (the resistome) at the microbiome-level is not well characterized. In this study, we applied whole metagenome sequencing (WMS) to characterize the resistome of the CM microbiome, focusing on antibiotics and metals resistance, biofilm formation (BF), and quorum sensing (QS) along with in vitro resistance assays of six selected pathogens isolated from the same CM samples. The WMS generated an average of 21.13 million reads (post-processing) from 25 CM samples that mapped to 519 bacterial strains, of which 30.06% were previously unreported. We found a significant (P = 0.001) association between the resistomes and microbiome composition with no association with cattle breed, despite significant differences in microbiome diversity among breeds. The in vitro investigation determined that 76.2% of six selected pathogens considered "biofilm formers" actually formed biofilms and were also highly resistant to tetracycline, doxycycline, nalidixic acid, ampicillin, and chloramphenicol and remained sensitive to metals (Cr, Co, Ni, Cu, Zn) at varying concentrations. We also found bacterial flagellar movement and chemotaxis, regulation and cell signaling, and oxidative stress to be significantly associated with the pathophysiology of CM. Thus, identifying CM microbiomes, and analyzing their resistomes and genomic potentials will help improve the optimization of therapeutic schemes involving antibiotics and/or metals usage in the prevention and control of bovine CM.


Opposite Auxin Dynamics Determine the Gametophytic and Embryogenic Fates of the Microspore.
The microspore can follow two different developmental pathways. In vivo microspores follow the gametophytic program to produce pollen grains. In vitro, isolated microspores can be reprogrammed by stress treatments and follow the embryogenic program, producing doubled-haploid embryos. In the present study, we analyzed the dynamics and role of endogenous auxin in microspore development during these two different scenarios, in Brassica napus. We analyzed auxin concentration, cellular accumulation, the expression of the TAA1 auxin biosynthesis gene, and the PIN1-like efflux carrier gene, as well as the effects of inhibiting auxin biosynthesis by kynurenine on microspore embryogenesis. During the gametophytic pathway, auxin levels and TAA1 and PIN1-like expression were high at early stages, in tetrads and tapetum, while they progressively decreased during gametogenesis in both pollen and tapetum cells. In contrast, in microspore embryogenesis, TAA1 and PIN1-like genes were upregulated, and auxin concentration increased from the first embryogenic divisions. Kynurenine treatment decreased both embryogenesis induction and embryo production, indicating that auxin biosynthesis is required for microspore embryogenesis initiation and progression. The findings indicate that auxin exhibits two opposite profiles during these two microspore developmental pathways, which determine the different cell fates of the microspore.


Selection of the most informative individuals from families with multiple siblings for association studies.
Association analyses may follow an initial linkage analysis for mapping and identifying genes underlying complex quantitative traits and may be conducted on unrelated subsets of individuals where only one member of a family is included. We evaluate two methods to select one sibling per sibship when multiple siblings are available: (1) one sibling with the most extreme trait value; and (2) one sibling using a combination score statistic based on extreme trait values and identity-by-descent sharing information. We compare the type I error and power. Furthermore, we compare these selection strategies with a strategy that randomly selects one sibling per sibship and with an approach that includes all siblings, using both simulation study and an application to fasting blood glucose in the Framingham Heart Study. When genetic effect is homogeneous, we find that using the combination score can increase power by 30-40% compared to a random selection strategy, and loses only 8-13% of power compared to the full sibship analysis, across all additive models considered, but offers at least 50% genotyping cost saving. In the presence of genetic heterogeneity, the score offers a 50% increase in power over a random selection strategy, but there is substantial loss compared to the full sibship analysis. In application to fasting blood sample, two SNPs are found in common for the selection strategies and the full sample among the 10 highest ranked single nucleotide polymorphisms. The EV strategy tends to agree with the IBD-EV strategy and the analysis of the full sample.


Brain areas activated after ejaculation in healthy young human subjects.
Brain mechanisms for the refractory period that characteristically follows ejaculation in animals and human are poorly understood. The possibility of active inhibition of brain areas being responsible for the post-ejaculatory inhibitory state has not been ruled out. Using Blood Oxygen Level Dependent (BOLD) functional magnetic resonance imaging (fMRI) we have mapped brain areas in healthy young volunteers immediately after ejaculation. Functional imaging of the brain for 30 minutes beginning after three minutes of ejaculation induced by masturbation showed spatio-temporal activation in amygdala, temporal lobes and septal areas. The septal areas were observed to be active for a shorter duration than the amygdala and the temporal lobe. Thus the temporal sequence of involvement of the above neural structures may contribute to temporary inhibition of sexual arousal/penile erection during the post-ejaculatory refractory period in humans.


Testicular Mixed Germ Cell Tumor Presenting with Upper Gastrointestinal Bleeding: A Case Report.
Testicular mixed germ cell tumors (TMGCTs) are aggressive neoplasms that often have metastases at the time of diagnosis, primarily in the lungs, bones, and brain. Gastrointestinal metastases are rare, occurring in less than 5% of cases, while duodenal involvement is extremely rare, with only few reported cases. Furthermore, gastrointestinal bleeding is an atypical initial presentation of metastatic TMGCTs. Herein, we present a very rare case of upper gastrointestinal bleeding caused by a duodenal metastasis of a TMGCT in a 24-year-old man. The patient was admitted to our hospital due to abdominal pain and melena with a hemoglobin level of 52 g/L. He had no history of testicular swelling, or any other symptoms or signs of a testicular tumor. Upper gastrointestinal endoscopy revealed a duodenal tumor mass with irregular bleeding, and abdominal ultrasound and computed tomography showed a duodenal mass that infiltrate retroperitoneum. Emergency surgery was performed, and the histopathological findings of the resected specimen were consistent with TMGCT metastasis. Subsequently, a testicular tumor was confirmed and surgically removed; however, multiple metastatic deposits were observed in the lungs. Due to the patient's poor general condition, chemotherapy was not performed. The patient died 3 months after the initial diagnosis. This case suggests that, although duodenal metastatic TMGCTs are rare, they should be considered in the differential diagnosis of gastrointestinal bleeding in young male patients.


Synergistic anticancer effects of curcumin and resveratrol in Hepa1-6 hepatocellular carcinoma cells.
Hepatocellular carcinoma remains one of the most prevalent malignancies worldwide. Curcuma aromatica and Polygonum cuspidatum are one of the commonly used paired-herbs for liver cancer treatment. Curcumin and resveratrol are the major anticancer constituents of Curcuma aromatica and Polygonum cuspidatum, respectively. Curcumin and resveratrol have been found to exhibit a synergistic anticancer effect in colon cancer. However, the combined effect of curcumin and resveratrol against hepatocellular carcinoma remains unknown. In the present study, we evaluated the combined effects of curcumin and resveratrol in hepatocellular carcinoma Hepa1-6 cells. The results showed that curcumin and resveratrol significantly inhibited the proliferation of Hepa1-6 cells in a dose- and time-dependent manner. The combination treatment of curcumin and resveratrol elicited a synergistic antiproliferative effect in Hepa1-6 cells. The apoptosis of Hepa1-6 cells induced by the combination treatment with curcumin and resveratrol was accompanied by caspase-3, -8 and -9 activation, which was completely abrogated by a pan caspase inhibitor, Z-VAD-FMK. Combination of curcumin and resveratrol upregulated intracellular reactive oxygen species (ROS) levels in Hepa1-6 cells. The ROS scavenger, NAC, partially attenuated the apoptosis and caspase activation induced by the combination treatment of curcumin and resveratrol. In addition, the combination of curcumin and resveratrol downregulated XIAP and survivin expression. These data suggest that the combination treatment of curcumin and resveratrol is a promising novel anticancer strategy for liver cancer. The present study also provides new insights into the effective mechanism of paired-herbs in traditional Chinese medicine.


Breeding experiments and genome-wide association analysis elucidate two genetically different forms of non-syndromic congenital cleft lip and jaw in Vorderwald × Montbéliarde cattle.
Non-syndromic congenital cleft lip and jaw (CLJ) is a condition reported in Vorderwald × Montbéliarde cattle. The objective of the present study was to perform a genome-wide association study (GWAS) for 10 CLJ-affected and 50 unaffected Vorderwald × Montbéliarde cattle using the bovine Illumina high density bead chip to identify loci for this condition. Phenotypic classification of CLJ was based on a detailed recording of orofacial structures using computed tomography. A breeding experiment among CLJ-affected Vorderwald × Montbéliarde cattle and CLJ-affected Vorderwald × Montbéliarde cattle with unaffected Holsteins confirmed recessive inheritance and different loci for bilateral or left-sided versus right-sided CLJ. The GWAS for the five cases with right-sided CLJ gave a genome-wide signal on bovine chromosome (BTA) 29 at 16 Mb. For the four left-sided and one bilateral CLJ case, a genome-wide significant association was identified on BTA4 at 32 Mb. Two different loci are very likely to be involved in CLJ in Vorderwald × Montbéliarde cattle because experimental matings among affected cows and bulls with different types of CLJ did not result in CLJ-affected progeny, and in addition, two different loci were also found through GWAS and mapped on two different bovine chromosomes. Validation in 346 Vorderwald × Montbéliarde cattle for the highly associated SNPs on BTA4 and 29 gave ratios of 33/346 (0.095, BTA4) and 6/346 (0.017, BTA29) homozygous mutant genotypes. Further studies should elucidate the responsible mutations underlying the different types of CLJ in Vorderwald × Montbéliarde cattle.


Suicide, suicide litigation, and borderline personality disorder.
In the category of malpractice liability affecting mental health practitioners of all disciplines, malpractice based on suicide is the leading claim by a significant margin. Our discussion here will be organized in two sections. First, we consider the theory, practice, and psychology of malpractice litigation itself in relation to suicide. Second, we describe how those basic principles apply to patients with borderline personality disorder.


Effects of Surgical Techniques on Long-Term Results in Patients with Degenerative Mitral Valve Bileaflet Prolapse.
The study aim was to evaluate the long-term results in patients with degenerative mitral valve bileaflet prolapse (DMVBLP) undergoing mitral valve repair (MVr) or mitral valve replacement (MVR), and to compare the consequences of survival related to each technique. Between 2001 and 2012, a total of 421 patients underwent isolated primary surgery for DMVBLP. MVr was performed in 146 patients (34.7%), and MVR in 275 (65.3%). MVR patients were allocated to two subgroups. Subgroup A were operated on in routine fashion, preserving the posterior subvalvular apparatus, and in selected cases the anterior or both apparatus (n = 119; 43.3%). In subgroup B, surgery was performed without preservation of the subvalvular apparatus (n = 156; 56.7%). There were no intraoperative deaths in all patient groups. The median length of follow up was 5.96 ± 3.28 years. Five patients (3.4%) in the MVr group died, while 11 in MVR subgroup A (9.2%) died, and 29 in MVR subgroup B (18.6%). Patients in the MVr group demonstrated significant and persistent postoperative decreases in left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD) during the follow up, while the left ventricular ejection fraction (LVEF) showed a trend to improve. In MVR subgroup A, preservation of the mitral subvalvular structures resulted in a decrease in LVEDD; this resulted in a lesser worsening of the LVEF, as occurs when subvalvular structures are resected. In MVR subgroup B, the LVEDD and LVESD were each increased constantly, which resulted in a statistically significant worsening of the LVEF. MVr in DMVBLP patients achieved a better preservation of left ventricular systolic indices than MVR, and guaranteed better shortand long-term survivals. When MVr is not feasible, it is recommended that subvalvular preservation be performed during MVR, in order to reduce the risk of early and late mortality and to improve left ventricular function.


Trends of caesarean sections for failure to progress: Indian rural experience.
The present observational study was carried out at a rural referral healthcare, educational institute in India. The objectives were to study the trends of contribution of caesarean section (CS) for failure-to-progress to the overall CS rate and their relationship to variables such as age, parity, stage of labour, augmentation of labour, in order to look at the trends and the scope for reduction in the CS for failure-to-progress and also the reduction in fetomaternal morbidity either by early intervention or reducing CS rates. Over 16 years, a total of 7,309 caesarean operations were performed, (contributing to 22.5% of births) and 533 (7.3%) were for failure-to-progress. The rate of CS for failure-to-progress was reduced in 2002 (5.0%), compared with 1992 (10.5%). The age of these women were similar to overall cases. A majority (346, 64.9%) of Sections for failure-to-progress were performed between 37 and 40 weeks of pregnancy, 125 (23.5%) between 41 and 42 weeks and only 62 (11.6%) were preterm. Rates of CS for failure-to-progress were 16.3% in primigravida and 8.8% in multipara, a decade ago, compared with 7.0% in primigravida and 2.8% in multipara now. Among the primigravida, 66 (18.3%) were performed in latent phase, 217 (60.3%) in the active first stage and 77 (21.4%) in the second stage of labour. Among multigravida, 35 (20.2%) were in the latent phase, 68 (39.3%) in the active first stage and 70 (40.5%) in the second stage. The authors were not always involved in the decisions to proceed to CS but probably because of the discussions before the observational study was undertaken, everyone involved with the decision making became concerned. So it seems critical evaluation of each CS before decision (keeping in mind materno-fetal well-being rather than hours), separating imminent labour from latent phase and higher doses of oxytocin should lead to a reduction in CS for failure-to-progress. Efforts need to be continued and should involve further research and evidence-based management strategies.


Biosynthesis and molecular cloning of sulfated glycoprotein 1 secreted by rat Sertoli cells: sequence similarity with the 70-kilodalton precursor to sulfatide/GM1 activator.
Sulfated glycoprotein 1 (SGP-1) is one of the abundant proteins secreted by rat Sertoli cells. Pulse-chase labeling shows that SGP-1 is synthesized as a cotranslationally glycosylated 67-kilodalton (kDa) precursor which is posttranslationally modified to a 70-kDa form before secretion to the extracellular space. A plasmid cDNA library was constructed from immunopurified mRNA, and two overlapping clones coding for the entire protein coding sequence were isolated. The cDNAs represent 27 nucleotides of 5' noncoding sequence, 1554 nucleotides of coding sequence, and 594 nucleotides of 3' noncoding sequence. The derived SGP-1 sequence contains 554 amino acids and has a molecular weight of 61,123. Four potential N-glycosylation sites occur within the sequence. An internal region of SGP-1 shows 78% sequence identity with the 67 N-terminal amino acids described for human sulfatide/GM1 activator (SAP-1). Sequence comparisons suggest that SGP-1 is the precursor to sulfatide/GM1 activator; however, the secretion of the protein from Sertoli cells is distinct from the proteolytic processing and lysosomal compartmentalization which have been described for human fibroblasts. The presence of internal sequence similarity suggests that three additional binding sites may occur in SGP-1. Northern blots show similar levels of expression for the 2.6-kilobase SGP-1 mRNA in all tissues examined. The site of SGP-1 synthesis in testis was localized to Sertoli cells by immunofluorescence and in situ hybridization.


Animal model for fragile X syndrome.
The fragile X syndrome, one of the most common forms of inherited mental retardation, is caused by an expansion of a polymorphic CGG repeat upstream of the coding region in the FMR1 gene. The expansion blocks expression of the FMR1 gene due to methylation of the FMR1 promoter. Functional studies on the FMR1 protein have shown that the protein can bind RNA and might be involved in transport of RNAs from the nucleus to the cytoplasm. A role of FMR1 protein on translation of certain mRNAs has been suggested. An animal model for fragile X syndrome exists and these mice show some behavioural difficulties mimicking the human fragile X syndrome phenotype. This review presents what is known about the protein and what is learned from the animal model for fragile X syndrome.


The hardest thing is the habit: a qualitative investigation of adolescent smokers' experience of nicotine dependence.
The aims were to explore adolescent smokers' understanding and their physiological and psychological experience of addiction to nicotine and to assess the content validity of the Hooked on Nicotine Checklist (HONC), a 10-item measure of nicotine dependence in youth. Six focus group interviews were conducted with male and female smokers recruited by school staff from among known smokers at one English and two French high schools in Montreal. Participants were 64 high-school students aged 14-17 years. Measurements were focus group discussion of smoking patterns and levels for self and others; feelings and sensations while smoking; physical and mental experiences of urges, feelings and sensations when smoking is prohibited; the physical, psychological, and social meanings of being hooked, dependent, or addicted; levels of dependence, desire to quit, and quit attempts. Participants readily identified nicotine dependence as relevant to their smoking experience. Dependence was described as the need to smoke, sometimes experienced as sensations of emptiness in the chest or blood and sometimes as a feeling in the mind. Smoking urges were often situationally determined and associated with hunger. With the exception of feeling sad, blue, or depressed on smoking withdrawal, participants endorsed almost all the symptoms in the HONC as relevant to their experience of dependence and identified several other symptoms as well. Adolescents are able to provide self-reports of symptoms of dependence that are consistent with a theoretically driven conceptualization of nicotine dependence. The HONC demonstrates content validity among adolescents but could be improved through removal of the item related to depression on withdrawal and possibly addition of items related to stress and appetite.


Aqua dissociation nature of cesium hydroxide.
To understand the mechanism of aqueous base dissociation chemistry, the ionic dissociation of cesium-hydroxide in water clusters is examined using density functional theory and ab initio calculations. In this study, we report hydrated structures, stabilities, thermodynamic quantities, dissociation energies, infrared spectra, and electronic properties of CsOH(H(2)O)(n=0-4). With the addition of water molecules, the Cs-OH bond lengthened significantly from 2.46 A for n=1 to 3.08 A for n=4, which causes redshift in Cs-O stretching frequency. It is found that three water molecules are needed for the dissociation of Cs-OH, in contrast to the case of strong acid dissociation which requires at least four water molecules. However, the dissociation for n=3 could be considered as incomplete because a very weak CS em leader OH stretch mode is still present, while that for n=4 is complete since the Cs em leader OH mode no longer exists. This study can be related with hydration chemistry of cations and anions, and extended into the intra- and intercharge-transfer phenomena.


Poisoning.
Knowledge of the toxicologic nature of ingested substances provides a proper framework for general and specific therapies best suited to meet the needs of the patient. Monitoring and direct observation provided in the PICU can aid proper therapy for many intoxicants. Good supportive care coupled with specific pharmacotherapy will provide the best chance for a successful outcome.


Trends in free WWW-based E-learning Modules seen from the Learning Resource Server Medicine (LRSMed).
Despite the lost enthusiasm concerning E-learning a lot of material is available on the World Wide Web (WWW) free of charge. This material is collected and systematically described by services like the Learning Resource Server Medicine (LRSMed) at http://mmedia.medizin.uni-essen.de/portal/. With the LRSMed E-learning modules are made available for medical students by means of a metadata description that can be used for a catalogue search. The number of resources included has risen enormously from 100 in 1999 up to 805 today. Especially in 2004 there was an exponential increase in the LRSMed's content. Anatomy is still the field with the highest amount of available material, but general medicine has improved its position over the years and is now the second one. Technically and didactically simple material as scripts, textbooks, and link lists (called info services) is still dominating. Similar to 1999, there is not one module which could be truly referred to as tutorial dialogue. Simple material can not replace face-to-face-teaching. But it could be combined with conventional courses to establish some kind of blending learning. The scene of free E-learning modules on the WWW is ready to meet current challenges for efficient training of students and continuing education in medicine.


[Toxicology of suicide cases in the state of Rio Grande do Sul, Brazil, 2017 to 2019Perfil toxicológico de los casos de suicidio en Rio Grande do Sul (Brasil), 2017-2019].
To describe the toxicology of suicide cases recorded in the state of Rio Grande do Sul, Brazil, from 2017 to 2019. The present descriptive, cross-sectional study examined all the medico-legal reports and police records related to suicide deaths in the state. Multiple correspondence analyses were performed along with independent logistic regression models having ethanol, anxiolytic and antidepressant drugs, illicit drugs, and non-medical substances as dependent variables. Ethanol was investigated in 2 978 samples, with positive results in 28.5%. The odds of a positive ethanol finding were 0.5 time higher (95%CI: 1.1; 2.2) for suicides occurring at night, 1.0 (95%CI: 1.4; 2.9) time higher for suicides occurring on weekends, and 0.9 (95%CI: 1.3; 2.7) time higher in individuals with a prior criminal record. Investigation of psychotropic drugs (2 900 samples) was positive in 30.4% samples. Anxiolytics were the most common medication detected, with 1.5 (95%CI: 1.6; 4.1) time higher odds of occurrence in women and 0.8 time higher odds (95%CI: 1.2; 2.7) for suicides occurring in the fall-winter. The odds of detecting illicit drugs (n = 338) were 4.1 times higher (95%CI: 1.9; 14.4) in the regions of Pelotas (south of the state) vs. Passo Fundo (north), and 1.2 (95%CI: 1.3; 3.6) time higher in cases with positive ethanol results, without significant difference between adolescents and adults. Despite the lack of evidence on causality, the present results support a link between suicide and several psychoactive drugs. Medico-legal experts should be guided regarding the need to perform toxicological tests in all suicide cases.


The role of the ESSS protein in the assembly of a functional and stable mammalian mitochondrial complex I (NADH-ubiquinone oxidoreductase).
The ESSS protein is a recently identified subunit of mammalian mitochondrial complex I. It is a relatively small integral membrane protein (122 amino acids) found in the beta-subcomplex. Genomic sequence database searches reveal its localization to the X-chromosome in humans and mouse. The ESSS cDNA from Chinese hamster cells was cloned and shown to complement one complementation group of our previously described mutants with a proposed X-linkage. Sequence analyses of the ESSS cDNA in these mutants revealed chain termination mutations. In two of these mutants the protein is truncated at the C-terminus of the targeting sequence; the mutants are null mutants for the ESSS subunit. There is no detectable complex I assembly and activity in the absence of the ESSS subunit as revealed by blue native polyacrylamide gel electrophoresis (BN/PAGE) analysis and polarography. Complex I activity can be restored with ESSS subunits tagged with either hemagglutinin (HA) or hexahistidine (His6) epitopes at the C-terminus. Although, the accumulation of ESSS-HA is not dependent upon the presence of mtDNA-encoded subunits (ND1-6,4 L), it is incorporated into complex I only in presence of compatible complex I subunits from the same species.


Kinetics of cardiac and vascular remodeling by spontaneously hypertensive rats after discontinuation of long-term captopril treatment.
Angiotensin-converting enzyme inhibitors reduce blood pressure and attenuate cardiac and vascular remodeling in hypertension. However, the kinetics of remodeling after discontinuation of the long-term use of these drugs are unknown. Our objective was to investigate the temporal changes occurring in blood pressure and vascular structure of spontaneously hypertensive rats (SHR). Captopril treatment was started in the pre-hypertensive state. Rats (4 weeks) were assigned to three groups: SHR-Cap (N = 51) treated with captopril (1 g/L) in drinking water from the 4th to the 14th week; SHR-C (N = 48) untreated SHR; Wistar (N = 47) control rats. Subgroups of animals were studied at 2, 4, and 8 weeks after discontinuation of captopril. Direct blood pressure was recorded in freely moving animals after femoral artery catheterism. The animals were then killed to determine left ventricular hypertrophy (LVH) and the aorta fixed at the same pressure measured in vivo. Captopril prevented hypertension (105 + or - 3 vs 136 + or - 5 mmHg), LVH (2.17 + or - 0.05 vs 2.97 + or - 0.14 mg/g body weight) and the increase in cross-sectional area to luminal area ratio of the aorta (0.21 + or - 0.01 vs 0.26 + or - 0.02 microm(2)) (SHR-Cap vs SHR-C). However, these parameters increased progressively after discontinuation of captopril (22nd week: 141 + or - 2 mmHg, 2.50 + or - 0.06 mg/g, 0.27 + or - 0.02 microm(2)). Prevention of the development of hypertension in SHR by using captopril during the prehypertensive period prevents the development of cardiac and vascular remodeling. Recovery of these processes follows the kinetic of hypertension development after discontinuation of captopril.


Effect of corticosterone on developing hippocampus: short-term and long-term outcomes.
Many documents implicate that corticosterone plays a negative role in brain function, especially in learning and memory. However, less evidence confirms its direct actions on hippocampal development. In the work reported here, pro treatment, minimum corticosterone administration in infant mice, and con treatment, corticosterone deprivation by adrenalectomy, were used to examine the effects imposed by corticosterone on the structure and function of developing hippocampus. Our study shows that adrenalectomy induces decrease of plasma corticosterone levels and results in the impairment of learning performance and the degenerative changes not in CA regions of hippocampus but in dentate gyrus. Noteworthily, this damage effect is severer in 5-week-old mice than that in 10-week-old mice. In addition, the short-term effect of minimum corticosterone administration may accelerate the development of dentate gyrus of 10-day-old mice. Moreover, minimum corticosterone administration during infancy contributed to the learning performance and the structural integrity of hippocampal CA regions in different developing stages, while this phenomenon was not observed in dentate gyrus. In conclusion, corticosterone is necessary for the development of dentate gyrus, especially in relatively young individuals, and administration with minimum corticosterone in infancy has a long-term positive influence on the hippocampal structure and function in different developing stages.


Spectral and photophysical studies of substituted indigo derivatives in their keto forms.
The spectral and photophysical properties of indigo derivatives with di-, tetra-, and hexa-substitution in their neutral (keto) form are investigated in solution. The study comprises absorption and emission spectra, together with quantitative measurements of quantum yields of fluorescence (phi(F)) and singlet oxygen formation (phi(Delta)) and fluorescence lifetimes. The energy difference between the HOMO and LUMO orbitals is dependent on the degree (number of groups) and relative position of substitution. The phi(F) and phi(Delta) values were found to be very low <or=10(-3). Because of the absence of transient triplet-triplet signal, the intersystem crossing yields (phi(T)) were estimated by assuming that all the triplet states formed give rise to singlet oxygen formation, that is, phi(Delta) approximately phi(T) . It was then possible from phi(IC)=1-phi(F)-phi(T) to estimate the S(1) approximately approximately -->S(0) internal conversion yields and thus, with the other data, to determine the rate constants for all decay processes. From these, several conclusions are drawn. Firstly, the radiationless rate constants, k(NR) , clearly dominate over the radiative rate constants, k(F) , (and processes). Secondly, the main deactivation channel for the compounds in their keto form is the radiationless S(1) approximately approximately -->S(0) internal conversion process. Finally, although the changes are relatively small, internal conversion yield seems to be independent of the overall pattern of substitution. A more detailed investigation of the decay profiles with collection at the blue and red emission of the fluorescence band of indigo and one di-substituted indigo reveals the decays to be bi-exponential and that at longer emission wavelengths these appear to be associated with both rise and decay times indicating that two excited species exist, which is consistent with a keto-excited form giving rise (by fast proton transfer) to the enol-form of indigo. Evidence is presented which supports the idea that intramolecular (and possibly some intermolecular) proton transfer can explain the high efficiency of internal conversion in indigo.


Surgical Treatment of Neglected Traumatic Quadriceps Tendon Rupture with Knee Ankylosis.
Quadriceps tendon rupture is an uncommon injury. This disabling condition is the result of direct or indirect trauma. It requires surgical repair to avoid poor outcomes in cases of neglected or chronic rupture. In most acute cases, simple tendon suture or reinsertion is suitable for an extensor mechanism reconstruction of the knee joint. However, chronic lesions often require a tendon graft or flap reconstruction. We report a case of a 15-year-old male who was diagnosed with a chronic quadriceps rupture with a patellar superior pole fracture. We performed quadriceps reconstruction using tibialis anterior allograft tendon and additional screw fixation to reconstruct the extensor mechanism and recover knee joint range of motion to prevent a high-level functional restriction. The treatment was difficult and limited due to neglect for 9-months that led to ankylosis accompanied with nonunion of tibial fracture. Our surgical treatment using allograft tendon resulted in a very good outcome after 30 months of follow-up.


Lower limb mechanical asymmetry during repeated treadmill sprints.
Stride mechanical imbalances between the lower limbs may be detrimental to performance and/or increase injury risks. This study describes the time course and magnitude of asymmetries in running mechanical variables during repeated treadmill sprints and examines whether inter-limb differences in sprinting mechanics increase with fatigue. Thirteen non-injured male athletes performed five 5-s sprints with 25-s recovery on an instrumented treadmill, allowing the continuous (step-by-step) measurement of running kinetics/kinematics and spring-mass characteristics calculation. For each variable, bilateral leg asymmetry (BLA%) between the left and the right leg was defined as: {[(high value-low value)/low value]×100}. BLA% for propulsive power and horizontal forces averaged ∼12-13%, while lower values occurred for step-averaged values of running velocity, resultant and vertical forces (all ∼4%). For all sprints, kinematic BLA% ranged from 1.6±1.0% (swing time) to 9.0±5.3% (aerial time). BLA% for vertical and leg stiffness was 6.4±4.9% and 7.6±3.6%, respectively. While distance covered decreased across repetitions (P<0.05), there was no significant interaction between sprint repetitions and leg side for any of the mechanical variables studied (all P>0.05). Although inter-limb differences were observed for many running kinetics/kinematics and spring-mass characteristics during repeated treadmill sprints, the lack of interaction between sprint repetitions and leg side suggests that lower limbs fatigued at a similar rate.


Adoption of the 2A Ribosomal Skip Principle to Tobacco Mosaic Virus for Peptide Display.
Plant viruses are suitable as building blocks for nanomaterials and nanoparticles because they are easy to modify and can be expressed and purified using plants or heterologous expression systems. Plant virus nanoparticles have been utilized for epitope presentation in vaccines, for drug delivery, as nanospheres and nanowires, and for biomedical imaging applications. Fluorescent protein fusions have been instrumental for the tagging of plant virus particles. The monomeric non-oxygen-dependent fluorescent protein iLOV can be used as an alternative to green fluorescent protein. In this study, the iLOV sequence was genetically fused either directly or via a glycine-serine linker to the C-terminus of the Tobacco mosaic virus (TMV) coat protein (CP) and also carried an N-terminal Foot-and-mouth disease virus (FMDV) 2A sequence. Nicotiana benthamiana plants were inoculated with recombinant viral vectors and a systemic infection was achieved. The presence of iLOV fusion proteins and hybrid particles was confirmed by western blot analysis and transmission electron microscopy. Our data suggest that TMV-based vectors are suitable for the production of proteins at least as large as iLOV when combined with the FMDV 2A sequence. This approach allowed the simultaneous production of foreign proteins fused to the CP as well as free CP subunits.


Lithium and the nephrotic syndrome.
The authors report the occurrence of the nephrotic syndrome in association with the use of lithium carbonate in a 41-year-old man, review other reports of this adverse effect, and discuss implications for the clinician.


End-of-Life Communication: Nurses Cocreating the Closing Composition With Patients and Families.
Communication is imperative for end-of-life decision-making; however, descriptions of key strategies used by nurses are missing. A phenomenological approach was used to interpret interviews from 10 hospice/palliative nurses. The overarching pattern is the closing composition. Key communication strategies/patterns include establishing context, acknowledging through attentive listening, making it safe for them to die, planning goals of care, and being honest. Essential is the awareness that nurse, patient, and family all hold expertise in the subject matter. It is imperative that pre-/postnursing licensure curriculum be expanded to include training in mutual influence communication practices and mentoring in the skill of orchestration.


Oleoylethanolamide: A fat ally in the fight against obesity.
Obesity is a pandemic, gateway disease that has thrived in modern, sedentary, high calorie-eating societies. Left unchecked, obesity and obesity-related diseases will continue to plague future generations with heavy burdens on economies, healthcare systems, and the quality of life of billions. There is a significant need to elucidate basic physiological mechanisms and therapies that address this global health care crisis. Oleoylethanolamide (OEA) is an endocannabinoid-like lipid that induces hypophagia and reduces fat mass in rodents. For over a decade, PPAR-α has been the most widely accepted mediator of the hypophagic action of OEA via signaling to homeostatic brain centers. Recent evidence suggests that OEA may also reduce food intake via effects on dopamine and endocannabinoid signaling within hedonic brain centers. Limited study of OEA supplementation in humans has provided some encouraging insight into OEA-based weight loss therapy, but more thorough, controlled investigations are needed. As a potential link between homeostatic and hedonic regulation of food intake, OEA is a prime starting point for the development of more effective obesity therapies.


Transcatheter aortic valve implantation in the United States: Predictors of early hospital discharge.
There is a concerted push for adopting a minimalist strategy with emphasis on early hospital discharge for patients undergoing Transcatheter aortic valve implantation (TAVI). However, studies on discharge patterns and predictors of early discharge (≤3 days post-TAVI) are sparse, in the United States. We analyzed using Healthcare Utilization Project, Nationwide Inpatient Sample database, 2011-2012. A total of 7321 TAVI procedures were identified. We compared in-hospital outcomes between early and late discharge cohorts, and determined the predictors of early discharge. Correlation of costs and post-TAVI length of stay was also performed. Early discharge rate post-TAVI was about 21% in the United States, in 2011-2012. Overall mean age was 81 years. In-hospital adverse outcomes post-TAVI were higher in late discharge cohort (P < 0.001). Mean length of stay post-TAVI (7.7 days vs 2.6 days) and costs ($208 752 vs $157 663) were significantly higher in late discharge than early discharge cohort. Females, bleeding, blood transfusions, stroke, permanent pacemakers, mechanical circulatory support, acute kidney injury were associated with significantly lower adjusted odds for early discharge. Transfemoral TAVI approach, prior aortic valvuloplasty, and procedure year 2012 were associated with significantly higher odds for early discharge. We observed positive correlation between costs of hospitalization and post-TAVI length of stay (R = 0.58; P < 0.001). Females, bleeding, blood transfusions, stroke, permanent pacemakers, mechanical circulatory support devices, renal failure were associated with lower odds for early discharge. Transfemoral approach and prior aortic valvuloplasty increased the likelihood for early discharge. Post-TAVI length of stay was associated with significantly higher hospitalization costs.


Lethality of the covalent linkage between mislocalized major outer membrane lipoprotein and the peptidoglycan of Escherichia coli.
The major outer membrane lipoprotein (Lpp) of Escherichia coli possesses serine at position 2, which is thought to function as the outer membrane sorting signal, and lysine at the C terminus, through which Lpp covalently associates with peptidoglycan. Arginine (R) is present before the C-terminal lysine in the wild-type Lpp (LppSK). By replacing serine (S) at position 2 with aspartate (D), the putative inner membrane sorting signal, and by deleting lysine (K) at the C terminus, Lpp mutants with a different residue at either position 2 (LppDK) or the C terminus (LppSR) or both (LppDR) were constructed. Expression of LppSR and LppDR little affected the growth of E. coli. In contrast, the number of viable cells immediately decreased when LppDK was expressed. Prolonged expression of LppDK inhibited separation of the inner and outer membranes by sucrose density gradient centrifugation, whereas short-term expression did not. Pulse-labeled LppDK and LppDR were localized in the inner membrane, indicating that the amino acid residue at position 2 functions as a sorting signal for the membrane localization of Lpp. LppDK accumulated in the inner membrane covalently associated with the peptidoglycan and thus prevented the separation of the two membranes. Globomycin, an inhibitor of lipoprotein-specific signal peptidase II, was lethal for E. coli only when Lpp possessed the C-terminal lysine. Taken together, these results indicate that the inner membrane accumulation of Lpp per se is not lethal for E. coli. Instead, a covalent linkage between the inner membrane Lpp having the C-terminal lysine and the peptidoglycan is lethal for E. coli, presumably due to the disruption of the cell surface integrity.


National Hospital Care Survey Demonstration Projects: Traumatic Brain Injury.
Purpose-This report demonstrates the analytical potential of the National Hospital Care Survey (NHCS) through a case study of inpatient discharges and ambulatory visits for traumatic brain injury (TBI) based on unweighted data from the 2013 NHCS of inpatient and emergency department (ED) encounters and the 2013 and 2014 NHCS for outpatient department (OPD) encounters.


Polyomavirus middle-sized tumor antigen modulates c-Jun phosphorylation and transcriptional activity.
Polyomavirus middle-sized tumor antigen (MT) increases the expression of c-jun through a phorbol 12-O-tetradecanoate 13-acetate response element in the c-jun promoter. To investigate the cellular signaling pathways affected by MT, we studied the role of the c-Ras and Raf-1 proteins in MT-induced transactivation of c-jun and cell transformation. There was an increase in GTP complexed to Ras in MT-expressing cells, indicating an increase in Ras activity. Coexpression of dominant inhibitory mutants of Ha-ras and raf-1 with MT inhibited MT-mediated transactivation and focus formation. Studies of the phosphorylation of c-Jun showed that MT expression increased the phosphorylation of Ser-63 and Ser-73 in the transactivation domain and decreased the phosphorylation of a peptide containing Ser-243, Ser-249, and Thr-231 in the DNA binding domain. MT increased the transcriptional activating ability of c-Jun but failed to increase the transcriptional activating ability of c-Jun mutants with Ser-63 and Ser-73 changed to nonphosphorylatable Ala, indicating that MT modulates c-Jun activity through phosphorylation. The dominant inhibitory mutants of Ha-ras and raf-1 interfered with the ability of MT to activate c-Jun. The results indicate that MT induces a phosphorylation cascade through the activation of c-Ras and Raf-1 and that c-Jun is one of the downstream targets that may cause changes in gene expression leading to cell transformation.


Specific differentiation of recombinant PVY(N:O) and PVY(NTN) isolates by multiplex RT-PCR.
The recombinant isolates of tobacco veinal necrotic strain of Potato virus Y (PVYN) and potato tuber necrotic group (PVY(NTN)) contain segments of the PVYO and the PVY(N) genome. Three major recombinant junctions (RJ) are present in the genome of the recombinant PVY(NTN) at sites HC/Pro-P3, 6K2-NIa, and the C-terminal region of CP gene and one RJ at HC/Pro-P3 site in some recombinant PVYN isolates (termed PVY(N:O)). Protocols for specific differentiation of the recombinant PVY(NTN) and PVY(N:O) from the non-recombinant PVYN are described. Specific primer pairs were designed to target the three RJs so that sense and antisense primers completely matched the nucleotide sequences at either side of the RJ. In a uniplex reverse transcription-polymerase chain reaction (RT-PCR), the first primer pair amplified a fragment of 641bp from the recombinant PVY(NTN) and PVY(N:O). The second and third primer pairs exclusively amplified fragments of 448 and 290bp, respectively from the recombinant PVY(NTN). In a multiplex (triplex) RT-PCR, when all three primer pairs were used simultaneously, the three fragments (641, 448 and 290bp) were amplified exclusively from the recombinant PVY(NTN), while only one fragment (641bp) was amplified from the PVY(N:O) isolates, clearly differentiating the two recombinant isolates. No amplification was observed from the non-recombinant PVY, including PVYO and North American (NA)-PVY(N/NTN). For further improvement of the multiplex RT-PCR, effects of cDNA preparation using specific antisense primers, random primers or oligo(dT) plus random primers were investigated. The cDNA prepared by random primer plus oligo(dT) increased the overall band intensity.


Scalping: the savage and the surgeon.
The treatment of the scalped patient has challenged and fascinated the surgeon for over two millennia. It is an esthetically disastrous mutilation, and the resultant soft tissue defect is a form of trauma calling for the surgeon's most creative efforts. The story of scalping is the story of innovative surgeons, both renowned and obscure, which parallels the development of plastic surgery.


Patterns of genetic connectedness between modern and medieval Estonian genomes reveal the origins of a major ancestry component of the Finnish population.
The Finnish population is a unique example of a genetic isolate affected by a recent founder event. Previous studies have suggested that the ancestors of Finnic-speaking Finns and Estonians reached the circum-Baltic region by the 1st millennium BC. However, high linguistic similarity points to a more recent split of their languages. To study genetic connectedness between Finns and Estonians directly, we first assessed the efficacy of imputation of low-coverage ancient genomes by sequencing a medieval Estonian genome to high depth (23×) and evaluated the performance of its down-sampled replicas. We find that ancient genomes imputed from >0.1× coverage can be reliably used in principal-component analyses without projection. By searching for long shared allele intervals (LSAIs; similar to identity-by-descent segments) in unphased data for >143,000 present-day Estonians, 99 Finns, and 14 imputed ancient genomes from Estonia, we find unexpectedly high levels of individual connectedness between Estonians and Finns for the last eight centuries in contrast to their clear differentiation by allele frequencies. High levels of sharing of these segments between Estonians and Finns predate the demographic expansion and late settlement process of Finland. One plausible source of this extensive sharing is the 8th-10th centuries AD migration event from North Estonia to Finland that has been proposed to explain uniquely shared linguistic features between the Finnish language and the northern dialect of Estonian and shared Christianity-related loanwords from Slavic. These results suggest that LSAI detection provides a computationally tractable way to detect fine-scale structure in large cohorts.


Host responses after acellular muscle basal lamina allografting used as a matrix for tissue engineered nerve grafts1.
A nerve gap must be bridged by autologous nerve grafts that serve as scaffold and consist of viable Schwann cells that promote regeneration. Owing to the necessary immunosuppression, nerve allografts remain limited to special cases. Alternatively, tissue engineering of peripheral nerves focuses on the implantation of cultured Schwann cells into suitable scaffolds. We established grafts from Schwann cells and basal lamina from acellular muscles. These grafts offer a regeneration that is comparable to autologous nerve grafts. Using a rat model (DALEW.1W strain), the present study evaluates the host response to acellular muscle allografts by assessing cellular reaction major histocompatability (MHC) class I and II, lymphocytes, macrophages. The results were compared to untreated muscle allografts. Macroscopically, the untreated muscles showed a strong inflammatory reaction as a sign of rejection, whereas the acellular muscle offered only minor reactions in the periphery of the graft. Expression of MHC I and II and invasion of CD4/CD8 positive cells and macrophages was pronounced after grafting the untreated muscles. Only a moderate reaction was noted for these parameters after acellular grafting. The acellular muscle graft is not completely free of cellular response; however the reaction is considered to be moderate and is located only in the periphery. To date, synthetic scaffolds that represent endoneurial tube-like structures and allow sufficient adhesion of Schwann cells and axonal regeneration are not available. The decreased response to acellular muscle allografts offers at least a basis for further experiments.


Oxidative Stress and Nutraceuticals in the Modulation of the Immune Function: Current Knowledge in Animals of Veterinary Interest.
In the veterinary sector, many papers deal with the relationships between inflammation and oxidative stress. However, few studies investigate the mechanisms of action of oxidised molecules in the regulation of immune cells. Thus, authors often assume that these events, sometime leading to oxidative stress, are conserved among species. The aim of this review is to draw the state-of-the-art of the current knowledge about the role of oxidised molecules and dietary antioxidant compounds in the regulation of the immune cell functions and suggest some perspectives for future investigations in animals of veterinary interest.


Antigen expression patterns of MYC-rearranged versus non-MYC-rearranged B-cell lymphomas by flow cytometry.
B-cell lymphomas with MYC rearrangement are a heterogeneous and unique group of neoplasms that may behave aggressively, especially in conjunction with other oncogenic alterations that cooperate with MYC, warranting early and intensive treatment in a subset of patients. Identification of MYC-rearranged B-cell lymphomas by immunophenotypic analysis could help guide cytogenetic work-up, as well as expedite therapeutic interventions. Using flow cytometry we analyzed the expression of CD10, CD19, CD20, CD38 and CD45 in 53 patients with three distinct neoplasms with MYC rearrangements: Burkitt lymphoma (n = 12), double hit lymphoma (n = 17) and diffuse large B-cell lymphoma (DLBCL) with MYC rearrangement (n = 8). The expression profile of these commonly used antibodies was similar among these three groups. The antigenic pattern of bright CD38 and dim CD45 was unique to the MYC-rearranged neoplasms when compared to non-MYC-rearranged aggressive DLBCL (n = 16), with a combined sensitivity of 67% and specificity of 100%, suggesting a shared underlying biology among these MYC rearranged B-cell lymphomas.


A recipe for mediocrity and disaster, in five axioms.
Biomedical research in the US will become unsustainable unless scientists and research institutions start to question certain assumptions they have long taken for granted.


Increasing NAD synthesis in muscle via nicotinamide phosphoribosyltransferase is not sufficient to promote oxidative metabolism.
The NAD biosynthetic precursors nicotinamide mononucleotide and nicotinamide riboside are reported to confer resistance to metabolic defects induced by high fat feeding in part by promoting oxidative metabolism in skeletal muscle. Similar effects are obtained by germ line deletion of major NAD-consuming enzymes, suggesting that the bioavailability of NAD is limiting for maximal oxidative capacity. However, because of their systemic nature, the degree to which these interventions exert cell- or tissue-autonomous effects is unclear. Here, we report a tissue-specific approach to increase NAD biosynthesis only in muscle by overexpressing nicotinamide phosphoribosyltransferase, the rate-limiting enzyme in the salvage pathway that converts nicotinamide to NAD (mNAMPT mice). These mice display a ∼50% increase in skeletal muscle NAD levels, comparable with the effects of dietary NAD precursors, exercise regimens, or loss of poly(ADP-ribose) polymerases yet surprisingly do not exhibit changes in muscle mitochondrial biogenesis or mitochondrial function and are equally susceptible to the metabolic consequences of high fat feeding. We further report that chronic elevation of muscle NAD in vivo does not perturb the NAD/NADH redox ratio. These studies reveal for the first time the metabolic effects of tissue-specific increases in NAD synthesis and suggest that critical sites of action for supplemental NAD precursors reside outside of the heart and skeletal muscle.


A QSAR Study on the 4-Substituted Coumarins as Potent Tubulin Polymerization Inhibitors.
Purpose: Despite the discovery and synthesis of several anticancer drugs, cancer is still a major life threatening incident for human beings after cardiovascular diseases. Toxicity, severe side effects, and drug resistance are serious problems of available commercial anticancer drugs. Coumarins are synthetic and natural heterocycles that show promising antiproliferative activities against various tumors. The aim of this research is to computationally study the coumarin derivatives in order to develop reliable quantitative structure-activity relationship (QSAR) models for predicting their anticancer activities. Methods: A data set of thirty one coumarin analogs with significant antiproliferative activities toward HepG2 cells were selected from the literature. The molecular descriptors for these compounds were calculated using Dragon, HyperChem, and ACD/Labs programs. Genetic algorithm (GA) accompanied by multiple linear regression (MLR) for simultaneous feature selection and model development was employed for generating the QSAR models. Results: Based on the obtained results, the developed linear QSAR models with three and four descriptors showed good predictive power with r2 values of 0.670 and 0.692, respectively. Moreover, the calculated validation parameters for the models confirmed the reliability of the QSAR models. Conclusion: The findings of the current study could be useful for the design and synthesis of novel anticancer drugs based on coumarin structure.


Emergence of cold water strawberry disease of rainbow trout Oncorynchus mykiss in England and Wales: outbreak investigations and transmission studies.
Cold water strawberry disease (CWSD), or red mark syndrome (RMS), is a severe dermatitis affecting the rainbow trout Oncorynchus mykiss. The condition, which presents as multifocal, raised lesions on the flanks of affected fish, was first diagnosed in Scotland in 2003 and has since spread to England and Wales. Results of field investigations indicated the condition had an infectious aetiology, with outbreaks in England linked to movements of live fish from affected sites in Scotland. Transmission trials confirmed these results, with 11 of 149 and 106 of 159 naive rainbow trout displaying CWSD-characteristic lesions 104 to 106 d after being cohabited with CWSD-affected fish from 2 farms (Farm B from England and Farm C from Wales, respectively). The condition apparently has a long latency, with the first characteristic lesions in the previously naive fish not definitively observed until 65 d (650 day-degrees) post-contact with affected fish. Affected fish from both outbreak investigations and the infection trial were examined for the presence of viruses, oomycetes, parasites and bacteria using a combination of techniques and methodologies (including culture-independent cloning of PCR-amplified bacterial 16S rRNA genes from lesions), with no potentially causative infectious agent consistently identified. The majority of the cloned phylotypes from both lesion and negative control skin samples were assigned to Acidovorax-like beta-Proteobacteria and Methylobacterium-like alpha-Proteobacteria.


The classification of anxiety and hysterical states. Part I. Historical review and empirical delineation.
The history of the classification of anxiety, hysterical, and hypochondriacal disorders is reviewed. Problems in the ability of current classification schemes to predict, control, and describe the relationship between the symptoms and other phenomena are outlined. Existing classification schemes failed the first test of a good classification model--that of providing categories that are mutually exclusive. The independence of these diagnostic categories from each other does not appear to hold up on empirical testing. In the absence of inherently mutually exclusive categories, further empirical investigation of these classes is obstructed since statistically valid analysis of the nominal data and any useful multivariate analysis would be difficult if not impossible. It is concluded that the existing classifications are unsatisfactory and require some fundamental reconceptualization.


Mycophenolate mofetil for the treatment of refractory auto-immune haemolytic anaemia and auto-immune thrombocytopenia purpura.
The treatment of both auto-immune haemolytic anaemia (AIHA) and auto-immune thromobocytopenic purpura (AITP) remains unsatisfactory in those refractory to first-line management. Mycophenolate mofetil (MMF) is an immunosuppressive agent originally used to prevent acute rejection of solid organ transplants and used more recently in the management of auto-immune conditions. We report its use in four patients with AIHA and six patients with AITP. All four patients with AIHA and five of the six patients with AITP showed a complete or good partial response to treatment with MMF, confirming a possible role in the treatment of these conditions.


Fibrin independent proinflammatory effects of tissue factor in experimental crescentic glomerulonephritis.
Tissue factor initiated glomerular fibrin deposition is an important mediator of injury in crescentic glomerulonephritis. Recent data have suggested noncoagulant roles for tissue factor in inflammation. To test the hypothesis that in addition to its effects in initiating coagulation, tissue factor has proinflammatory effects in glomerulonephritis, rabbits given crescentic anti-glomerular basement membrane (GBM) antibody-induced glomerulonephritis were defibrinogenated with ancrod. One group of defibrinogenated rabbits was also given anti-tissue factor antibodies. Comparisons were made between these groups, as well as a third group that was neither defibrinogenated with ancrod nor given anti-tissue factor antibodies. Defibrinogenation alone abolished glomerular fibrin deposition, reduced crescent formation, and limited renal impairment (ancrod-treated, serum creatinine 274 +/- 37 micromol/L; untreated 415 +/- 51 micromol/L; P < 0.01). Tissue factor inhibition in defibrinogenated rabbits resulted in further protection of renal function (creatinine 140 +/- 19 micromol/L, P < 0.01) and reduced proteinuria (0.4 +/- 0.2g/day, untreated 2.6 +/- 0.4 g/day, P <0.01), which was significantly increased by defibrinogenation alone (ancrod-treated, 5.6 +/- 1.2 g/day). Anti-tissue factor antibodies (but not defibrinogenation alone) attenuated glomerular T-cell and macrophage recruitment, and major histocompatibility complex (MHC) class II expression. These results demonstrate important proinflammatory effects of tissue factor in crescentic glomerulonephritis that are fibrin independent and provide in vivo evidence for tissue factor's proinflammatory effects on MHC class II expression and leukocyte accumulation.


Perspectives on Early Power Mobility Training, Motivation, and Social Participation in Young Children with Motor Disabilities.
The efficacy of traditional training programs (e.g., neurodevelopmental therapy) in promoting independent mobility and early child development across all three International Classification of Functioning, Disability, and Health levels lacks rigorous research support. Therefore, early power mobility training needs to be considered as a feasible intervention for very young children who are unlikely to achieve independent mobility. This perspective article has three aims: (1) to provide empirical evidence of differences in early independent mobility, motivation, daily life activities, and social participation between young children with typical development and motor disabilities; (2) to discuss the contemporary concepts of and approaches to early power mobility training for young children with motor disabilities and the current need for changes to such training; and (3) to provide recommendations for early power mobility training in pediatric rehabilitation. Independent mobility is critical for social participation; therefore, power mobility can be accessible and implemented as early as possible, specifically for infants who are at risk for mobility or developmental delay. To maximize the positive effects of independent mobility on children's social participation, early power mobility training must consider their levels of functioning, the amount of exploration and contextual factors, including individual and environmental factors.


Phenotype and Cellular Response of Wheat Lines Carrying Cre Genes to Heterodera avenae Pathotype Ha91.
The cereal cyst nematode (CCN, Heterodera avenae), a major limiting factor for wheat production worldwide, is widespread in most wheat-growing regions in China. Accordingly, screening and characterization of resistant (R) wheat sources against H. avenae are very important. In this study, we screened 51 wheat lines, collected from the International Wheat and Maize Improvement Center (CIMMYT), carrying various Cre genes (Cre1, Cre2, Cre3, Cre5, Cre7, Cre8, CreR, and Pt). From that screen, we identified one immune (M) cultivar (with no adult females produced) and five resistant cultivars (with fewer than five females) to H. avenae pathotype Ha91. The Cre3 gene conferred the most effective resistance against H. avenae pathotype Ha91 in both field and greenhouse assays. Conversely, the Cre1 and CreR genes conferred the poorest effective resistance. Using Pluronic F-127 gel and a staining assay, juvenile nematodes invading wheat roots were observed, and nematode development was analyzed. Compared with R and M roots, those of the susceptible (S) wheat cultivar Wenmai19 were more attractive to H. avenae second-stage juveniles (J2s). We observed the retardation of nematode development in R cultivars and tiny white female cysts protruding from the R cultivar VP1620. Nematodes in M roots either disintegrated or remained J2s or third-stage juveniles (J3s) and failed to complete their life cycle. Molting was also suppressed or delayed in R and M genotypes. For both S and R cultivars, syncytia were characterized by cell wall perforations and dense cytoplasm in hypertrophied syncytium component cells. Syncytial size increased gradually with nematode development in S cultivars. Moreover, an incompatibility reaction occurred in M wheat roots: the syncytium was disorganized, exhibiting disintegration and condensed nuclei. These sources of genetic resistance against CCN can potentially be planted in severely infested fields to reduce economic loss or can be used for introgression in breeding.


Tanshinone IIA Alleviates the AD Phenotypes in APP and PS1 Transgenic Mice.
Therapeutic approach for Alzheimer's disease (AD) is still deficient. To find active compounds from herbal medicine is of interest in the alleviation of AD symptoms. This study aimed to investigate the protective effects of Tanshinone IIA (TIIA) on memory performance and synaptic plasticity in a transgenic AD model at the early phase. 25-100 mg/kg TIIA (intraperitoneal injection, i.p.) was administered to the six-month-old APP and PS1 transgenic mice for 30 consecutive days. After treatment, spatial memory, synaptic plasticity, and related mechanisms were investigated. Our result showed that memory impairment in AD mice was mitigated by 50 and 100 mg/kg TIIA treatments. Hippocampal long-term potentiation was impaired in AD model but rescued by 100 mg/kg TIIA treatment. Mechanically, TIIA treatment reduced the accumulations of beta-amyloid 1-42, C-terminal fragments (CTFs), and p-Tau in the AD model. TIIA did not affect basal BDNF but promoted depolarization-induced BDNF synthesis in the AD mice. Taken together, TIIA repairs hippocampal LTP and memory, likely, through facilitating the clearance of AD-related proteins and activating synaptic BDNF synthesis. TIIA might be a candidate drug for AD treatment.


[Varicella: how and when to start antiviral treatment].
The Meeting "An Update on Chickenpox" (Florence, 19-3-1993) has contributed to verify, in the light of the most recent acquisitions, the new guidelines for a correct rationale in the diagnosis and therapy of chickenpox. The present availability of an effective specific antiviral therapy for chickenpox (acyclovir) leads to a careful selection of patients to be treated. The high incidence of chickenpox morbidity keeps long unaltered and, beyond the usually benign onset of the primary infection in the child, the severity of this pathology in particular subjects and situations at risk is to be certainly underlined. Treatment is suggested for cases of chickenpox contracted inside the family. Generally, boys are at higher risk. Adolescents and adults, usually with a lower incidence, report a much higher severity of the acute onset and complications. Another category to be certainly treated is the one--in constant increase--of immunocompromised subjects. In any case, acyclovir treatment improves the symptomatologic evolution (pruritus and fever) and duration of clinical course. Among the progenitors of acyclovir, Valacyclovir seems to have the best prospects of success for the immediate future of antiviral therapy.


Cytology of bronchial washings: a study of patients with malignant neoplasms of the head and neck.
Among 18 patients with locally advanced malignant neoplasms of the head and neck region, bronchial washings failed to reveal tumor cells despite the demonstration of exfoliated tumor cells in washings from the region of the primary tumor in 13 (72 percent) of the patients. Among 17 patients with bronchogenic carcinomas, however, tumor cells were isolated from the bronchial washings in 14 (82 percent). These results indicate that, in patients with malignant neoplasms of the head and neck, tumor cells found in bonchial washings probably are not from the primary head and neck neoplasms. Thus, cytologic examination of bronchial washings may be validly employed in the differential diagnosis of the pulmonary tumors in patients with malignant neoplasms of the head and neck region.


Immunogenicity of two FMDV nonameric peptides encapsulated in liposomes in mice and the protective efficacy in guinea pigs.
It has been predicted that nonameric peptides I (VP1(26-34), RRQHTDVSF), II (VP1(157-165), RTLPTSFNY) and III (VP1(45-53), KEQVNVLDL) from the VP1 capsid protein of the foot-and-mouth disease virus (FMDV) are T cell epitopes. To investigate whether these peptides have immunological activity, BALB/c mice were immunized with peptide I, II or III conjugated with immunostimulating complexes (ISCOMs). A cytotoxic T lymphocyte assay was used to evaluate the cytotoxic activity induced by peptides along with by measuring peptide-specific T-cell proliferation and CD8(+) T lymphocyte numbers in whole blood and interferon (IFN)-γ production in peripheral blood mononuclear cells induced by peptides. To further identify the protective efficacy of peptides, an FMDV challenge assay was done in guinea pigs. Peptides I and II stimulated significant increases in T-cell proliferation, CD8(+) T lymphocytes, and IFN-γ secretion and cytotoxic activity compared to controls. The FMDV challenge assay indicated peptides I and II can protect over 60% of animals from virus attack. The results demonstrate that peptides I and II encapsulated in liposomes should be CTL epitopes of FMDV and can protect animals from virus attack to some extent.


Position paper on olfactory dysfunction: 2023.
Since publication of the original Position Paper on Olfactory Dysfunction in 2017 (PPOD-17), the personal and societal burden of olfactory disorders has come sharply into focus through the lens of the COVID-19 pandemic. Clinicians, scientists and the public are now more aware of the importance of olfaction, and the impact of its dysfunction on quality of life, nutrition, social relationships and mental health. Accordingly, new basic, translational and clinical research has resulted in significant progress since the PPOD-17. In this updated document, we present and discuss currently available evidence for the diagnosis and management of olfactory dysfunction. Major updates to the current version include, amongst others: new recommendations on olfactory related terminology; new imaging recommendations; new sections on qualitative OD and COVID-19 OD; updated management section. Recommendations were agreed by all co-authors using a modified Delphi process. We have provided an overview of current evidence and expert-agreed recommendations for the definition, investigation, and management of OD. As for our original Position Paper, we hope that this updated document will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency, and generalisability of work in this field.


Aortic valve calcification: determinants and progression in the population.
Aortic valve calcification (AVC) is considered degenerative. Recent data suggested links to atherosclerosis or coronary disease (CAD). AVC and coronary artery calcifications (CAC) were prospectively assessed by Electron-Beam-Computed-Tomography in 262 population-based research participants > or = 60 years. AVC was frequent (27%) with aging (P<0.01) and in men (P<0.05). AVC was associated with diabetes, hypertension, higher body-mass-index, and serum glucose (all P<0.05). AVC was a marker of higher prevalence (P<0.01) and severity of CAD (CAC score: 441+/-802 versus 265+/-566, P<0.05) independently of age. After follow-up of 3.8+/-0.9 years, AVC score increased (94+/-271 versus 54+/-173, P<0.01, +11+/-32 U/year), faster with higher baseline AVC score (P<0.01). Compared with participants remaining free of AVC, de novo acquisition of AVC was associated with higher LDL-cholesterol (141+/-31 versus 121+/-27 mg/dL, P<0.05) and faster CAC progression (+78+/-87 versus +28+/-47 U/year, P<0.05). In multivariate analysis, LDL-cholesterol independently determined AVC acquisition while higher baseline AVC scores determined faster progression of existing AVC. In the population, AVC is frequent with aging and atherosclerotic risk factors. AVC is a marker of subclinical CAD. AVC is progressive, appearing de novo with progressive atherosclerosis whereas established AVC progresses independently of atherosclerotic risk factors and faster with increasing initial AVC loads.


Major congenital malformations among neonatal referrals to a Nigerian university hospital.
Major congenital malformations are unrecognised as a major cause of neonatal morbidity in many African countries. We have studied the contribution of major congenital malformations to morbidity among neonates referred to the University College Hospital, Ibadan, Nigeria over a four year period (1992-1995). Major congenital malformations were found in 11.1% of 1276 neonatal referrals and ranked fourth among the most common problems in such neonates (after sepsis, jaundice and tetanus but ahead of prematurity and perinatal asphyxia). The commonest malformations seen included spina bifida (22.5%), anorectal malformation (13.4%), omphalocoele (9.9%) and tracheo-oesophageal fistula (8.5%). Neonates with major congenital malformations presented significantly earlier than other neonates but mortality during the first admission was similar in the two groups. It is concluded that major congenital malformations pose a significant burden of morbidity in referred neonates to the hospital. Health services planners should take this into account in order to allocate the necessary resources for the diagnosis and management of such children.


Prediction of jet mixing noise with Lighthill's Acoustic Analogy and geometrical acoustics.
A computational aeroacoustics prediction tool based on the application of Lighthill's theory is presented to compute noise from subsonic turbulent jets. The sources of sound are modeled by expressing Lighthill's source term as two-point correlations of the velocity fluctuations and the sound refraction effects are taken into account by a ray tracing methodology. Both the source and refraction models use the flow information collected from a solution of the Reynolds Averaged Navier-Stokes equations with a standard k-epsilon turbulence model. By adopting the ray tracing method to compute the refraction effects a high-frequency approximation is implied, while no assumption about the mean flow is needed, enabling the application of the method to jet noise problems with inherently three-dimensional propagation effects. Predictions show good agreement with narrowband measurements for the overall sound pressure levels and spectrum shape in polar angles between 60° and 110° for isothermal and hot jets with acoustic Mach number ranging from 0.5 to 1.0. The method presented herein can be applied as a relatively low cost and robust engineering tool for industrial optimization purposes.


In situ observation of phase transformation in an Fe-Zn system at high temperatures using an image plate.
A unique system has been developed for in situ observation of phase transformation at high temperatures. Changes in powder-diffraction patterns from a heated specimen can be measured continuously by scanning an image plate located behind a slit. A heating system has been designed for a sheet specimen ( approximately 5 x 6 mm) using Joule heating, and it can heat the specimen up to 1100 K at a rate of up to 160 K s(-1), where effects of thermal expansion are minimized by a mechanism releasing stress. This system was applied to Zn-coated ( approximately 8 micro m in thickness) steel. At temperatures higher than the melting point of Zn, different types of Fe-Zn intermetallics formed sequentially through rapid interdiffusion. Changes in phase and crystallographic structure were monitored with a time resolution of less than a few seconds. It has been found that an addition of a small amount of an element, such as P, into Fe changes the incubation time before the alloying reaction starts. This system has been shown to have the potential for application to in situ observation of other reactions at high temperatures.


Cemented versus uncemented total knee arthroplasty in younger patients: A protocol of retrospective cohort trial.
Recently, controversy still exists regarding the clinical effects of cemented or cementless technique in young patients in total knee arthroplasty (TKA). In this context, the present study aimed to determine the functional outcomes and clinical reliability of cementless components versus those of conventional cemented components for young patients in primary TKA. A retrospective review of primary TKAs performed with cementless or cemented fixation between May 2010 and February 2019 was conducted with Institutional Review Board approval. All cases were performed by a single surgeon. Institutional review board approval was obtained prior to conducting chart review and analysis. The primary outcome compared between the 2 fixation groups was the rate of postoperative complications and revision related to TKA, occurring at any point in follow-up. Secondary outcome measures included surgical time, Oxford Knee Score, range of motion, and radiographic outcomes such as progressive radiolucent lines, osteolysis, or component migration. We were able to directly compare the outcomes of cemented versus cementless techniques and might reveal a better technique in TKA. This study protocol was registered in Research Registry (researchregistry5459).


DNA plasticity and damage in amyotrophic lateral sclerosis.
The pathophysiology of amyotrophic lateral sclerosis (ALS) is particularly challenging due to the heterogeneity of its clinical presentation and the diversity of cellular, molecular and genetic peculiarities involved. Molecular insights unveiled several novel genetic factors to be inherent in both familial and sporadic disease entities, whose characterizations in terms of phenotype prediction, pathophysiological impact and putative prognostic value are a topic of current researches. However, apart from genetically well-defined high-confidence and other susceptibility loci, the role of DNA damage and repair strategies of the genome as a whole, either elicited as a direct consequence of the underlying genetic mutation or seen as an autonomous parameter, in the initiation and progression of ALS, and the different cues involved in either process are still incompletely understood. This mini review summarizes current knowledge on DNA alterations and counteracting DNA repair strategies in ALS pathology and discusses the putative role of unconventional DNA entities including transposable elements and extrachromosomal circular DNA in the disease process. Focus is set on SOD1-related pathophysiology, with extension to FUS, TDP-43 and C9ORF72 mutations. Advancing our knowledge in the field will contribute to an improved understanding of this relentless disease, for which therapeutic options others than symptomatic approaches are almost unavailable.


High dose ARA-C as induction therapy of acute myeloid leukaemia.
Twenty-one newly diagnosed adult AML patients were treated with high dose Ara-C (HD-ARA-C) as a single induction treatment with the dose of 2 g/m2 q 12 hours x 12. Seventy-six percent (16/21) responded with complete remission. Three patients died in induction in pancytopenia, another one died on day 44 in CR due to bleeding of pulmonary aspergilloma. This treatment seems to be highly efficient for remission induction, but requires an adequate transfusion and other supportive measures. The overall toxicity was transient and seems acceptable. However, the remission duration is unacceptably short, the consolidation with the same treatment seems to be inadequate. More aggressive treatment in postinduction period seems to be warranted.


A spectrum of biophysical interaction modes between T cells and different antigen-presenting cells during priming in 3-D collagen and in vivo.
For activation T cells engage antigen-presenting cells (APCs) in lymphatic tissues. The contact duration and kinetics (static versus dynamic) vary considerably in different model systems; however, it is unclear whether T cells, APCs, or the environment are responsible for the observed discrepancies. Using 3-D collagen matrices as structural scaffold, we directly compared the kinetics of T-cell engagement and activation by functionally major APC types, ie, dendritic cells (DCs) and resting or activated B cells. Resting B cells engaged T cells in long-lived (several hours), adhesive, and leukocyte function-associated antigen-1 (LFA-1)-dependent conjugates in 3-D collagen as well as in intact lymph nodes in vivo. DCs and preactivated B cells, however, supported predominantly dynamic, short-lived (minutes), and sequential contacts to T cells that were dependent on high cytoskeletal activity of the APCs but could not be inhibited by anti-LFA-1 treatment. Naive T cells were most strongly activated by DCs and activated B cells, whereas resting B cells were 100-fold less efficient to induce T-cell proliferation. Thus, in the same 3-D environment, naive T cells respond with a spectrum of different interaction modes dependent on the type and activation state of the APCs. Thereby, more dynamic interaction kinetics is positively correlated with higher T-cell priming efficiency.


Perceptually regulated training does not influence the differentiated RPE response following 16-weeks of aerobic exercise in adults with spinal cord injury.
This study investigated the effect of prolonged familiarisation with ratings of perceived exertion (RPE) on the peripheral (RPEP) and central (RPEC) RPE responses to moderate-vigorous exercise in adults with spinal cord injury (SCI). RPEP and RPEC characterise the exertion of the working musculature and cardiorespiratory systems, respectively. Nineteen participants (age, 41.4 ± 11.4 years; peak oxygen uptake, 19.2 ± 7.2 mL·kg-1·min-1) with chronic SCI were randomly assigned to RPE-guided (n = 11; EXP) or active control (n = 8; CON) groups. EXP performed 16-weeks of RPE-guided, supervised aerobic training for 20 min, twice weekly, at RPE 3-6 (Category-Ratio 10 scale). CON had access to the same exercise equipment but received no specific advice on their exercise-training regime. Participants completed a graded exercise test, using an arm crank ergometer at pre- and post-training to determine peak oxygen uptake, with RPEP and RPEC recorded every minute throughout tests. Sixteen weeks training did not improve peak oxygen uptake. RPE decreased post-training at 50% (p = 0.02) and 70% peak oxygen uptake (p = 0.03), though there was no effect of group at either intensity (p = 0.54, 0.42, respectively). At 70% peak oxygen uptake, RPEP was greater than RPEC (4.2 ± 1.7 vs 3.4 ± 1.8, p < 0.005). Training with RPE-guidance for 16 weeks had no additional effect on the differentiated RPE responses to moderate-vigorous exercise in adults with SCI. Novelty In adults with SCI, differentiated RPE responses were not different between those who did, and did not, perform 16 weeks of RPE-guided training. This challenges whether familiarisation with RPE is necessary to be an effective regulator of exercise intensity in this population.


Sweet sixteen: changing time preferences in the transition from middle school to high school, for different scenarios.
Teenagers earn, save and spend large amounts of money. Therefore, understanding teenagers' time preference and how it affects their economic behavior is very important. The current study investigates time preferences of high school and middle school students, and the effect of different intertemporal choice scenarios on teenagers' subjective discount rate. One scenario used a standard intertemporal choice question while the other was a wage scenario. We found higher future orientation (lower subjective discount rate) among high school students than among middle school students when using a standard scenario but found no difference between groups in the wage scenario. For both groups, we found the subjective discount rates increased when the teenagers are asked to delay receipt of wages they earned by working (wage scenario). Other variables, like participation in sports and an allowance given by parents, were found to affect teenagers' time preferences.


Diagnostic and treatment strategy for small gastrointestinal stromal tumors.
Gastrointestinal stromal tumors (GISTs) are considered to be potentially malignant mesenchymal tumors of the gastrointestinal tract. Clinically relevant GISTs are rare; however, subclinical GISTs (mini-GISTs) (1-2 cm) and pathologic GISTs (micro-GISTs) (<1 cm) are frequently reported. Most mini-GISTs and almost all micro-GISTs of the stomach may exhibit benign clinical behavior, and only mini-GISTs with high-risk features may progress. For this review, a provisional algorithm was used to propose diagnostic and treatment strategies for patients with small GISTs. Because surgery is the only potentially curative treatment, in its application for small GISTs, the principles of sarcoma surgery should be maintained, and cost effectiveness should be considered. Indications for surgery include GISTs measuring ≥2 cm, symptomatic GISTs, and mini-GISTs with high-risk features (irregular borders, cystic spaces, ulceration, echogenic foci, internal heterogeneity, and tumor progression during follow-up); however, a preoperative pathologic diagnosis is infrequently obtained. For small intestinal and colorectal GISTs, surgery is indicated irrespective of size because of their greater malignant potential. Otherwise, mini-GISTs without high-risk features, micro-GISTs, and small submucosal tumors measuring <5 cm without high-risk features may be followed by periodical endoscopic ultrasonography. Although surgical approaches and operative methods are selected according to tumor size, location, growth pattern, and surgical teams, laparoscopic surgery has produced similar oncologic outcomes and is less invasiveness compared with open surgery. After resection, pathologic examination for diagnosis and risk assessment is mandatory, and genotyping is also recommended for high-risk GISTs. Endoscopic resection techniques, although feasible, are not routinely indicated for most mini-GISTs or micro-GISTs. Cancer 2016;122:3110-8. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.


1,1,6-Trimethyl-1,2-dihydronaphthalene Content of Riesling Wines in Hungary.
1,1,6-Trimethyl-1,2-dihydronaphthalene (TDN) is known to give a petrol note when smelling and tasting wine, which is most pronounced in Riesling varieties. Its increasing concentration has been linked to climate change. In the present work, a gas chromatographic method was used to quantify free TDN in "Italian Riesling", "Rhine Riesling", and "Kéknyelű" wines from Hungary. From the vintages 2010 to 2020, 39 bottles of wine from different wine regions were evaluated by instrumental analysis and sensory evaluation. Our aim is to determine the extent to which the Riesling wines in Hungary show a petrol character. The other objective was a comparison of sorts to see if there is a difference in TDN production potential between Italian Riesling and Rhine Riesling. We also aimed to clarify the question whether the Hungarian variety Kéknyelű is also capable of developing a petrol character. The wines we tested were corked and screw-locked. This allowed us to compare the difference in TDN concentration variation over time between the two closure methods.


Decompensated Cirrhosis and Sickle Cell Disease: Case Reports and Review of the Literature.
Although its prevalence is unknown, liver involvement by sickle cell disease is not uncommon and encompasses different clinical spectra including non cholestatic and cholestatic disorders. Few data have been provided on chronic sickle cell intrahepatic cholestasis (SCIC) clinical course, although cirrhosis has been reported in sickle cell disease. However, no effective therapeutic approaches have been recognized either to prevent or treat this condition. Here we present two cases of adult sickle cell disease patients with decompensated cirrhosis. Their liver biopsies showed sickle cell thrombi within the hepatic sinusoids. Despite erythroexchange (EEX) transfusions, both patients suffered from major sickle cell disease-related events, suggesting that EEX transfusions may not be enough to impact on advanced liver involvement by sickle cell disease.


A methyl methacrylate-HEMA-CL(n) copolymerization investigation: from kinetics to bioapplications.
The radical copolymerization kinetics of methyl methacrylate (MMA) and poly-ϵ-caprolactone macromonomer functionalized with a vinyl end group (HEMA-CL(n)) is studied using a pulsed-laser technique. The reactivity ratios for this system are near unity, while a linear relationship between k(p,cop), the copolymer-averaged propagation rate coefficient, and the composition of macromonomer in the feed (0-80 wt% range) is determined. At 50 wt% macromonomer in the feed, a 1.67 ± 0.02 and 1.64 ± 0.06 increase in k(p,cop)/k(p,MMA) is determined for HEMA-CL3 and HEMA-CL2, respectively. These macromonomers are adopted to synthesize nanoparticles (NPs) in the range of 100-150 nm through batch emulsion free radical polymerization (BEP) to produce partially degradable drug delivery carriers. The produced NPs are tested in 4T1 cell line and show excellent characteristics as carriers: they do not affect cell proliferation, and a relevant number of NPs, thousands per cell, are internalized.


Unexpected toxic interactions in the freshwater amphipod Gammarus pulex (L.) exposed to binary copper and nickel mixtures.
To document the toxicity of copper and nickel in binary mixtures, freshwater amphipods Gammarus pulex were exposed to the metals given independently or as mixtures. Toxicity to Cu alone was relatively high: 96-h LC10 and LC50 were found at 91 and 196 μg L(-1), respectively. Toxicity to Ni alone was very low, with 96-h LC10 and LC50 of 44,900 and 79,200 μg L(-1), respectively. Mixture toxicities were calculated from single toxicity data using conventional models. Modeled toxicity was then compared with the measured toxicity of the binary mixture. Two kinds of mixtures were tested. Type I mixtures were designed as combinations of Cu and Ni given at the same effect concentrations, when taken independently, to identify possible interactions between copper and nickel. In type II mixtures, Cu concentrations varied from 0 to 600 μg L(-1) while the nickel concentration was kept constant at 500 μg L(-1) to mimic conditions of industrial wastewater discharges. Ni and Cu showed synergic effects in type I mixtures while type II mixtures revealed antagonistic effects. Low doses of Ni reduced Cu toxicity towards G. pulex. These results show that even for simple binary mixtures of contaminants with known chemistry and toxicity, unexpected interactions between the contaminants may occur. This reduces the reliability of conventional additivity models.


Binding of the chymotrypsin substrate, tryptophan methyl ester, by rat alpha-fetoprotein.
We studied how tryptophan methyl ester and related compounds inhibit binding of estrone to rat alpha-fetoprotein and find that: (a) like chymotrypsin, alpha-fetoprotein binds tryptophan esters with higher affinity than tryptophan or its amides; (b) the affinity of alpha-fetoprotein for tryptophan methyl ester is 3.7 . 10(-4) M, which is close to the affinity of chymotrypsin (10(-4) M); (c) alpha-fetoprotein binding of tryptophan methyl ester is stereoselective and pH dependent. All of these observations suggest that there is a specific interaction between alpha-fetoprotein and the chymotrypsin substrate, tryptophan methyl ester, and that rat alpha-fetoprotein contains a site with some structural similarities to the catalytic site in chymotrypsin. Since we also find that tryptophan methyl ester is a competitive inhibitor of estrone binding to alpha-fetoprotein, it is possible that the protease substrate binding site on alpha-fetoprotein is spatially close to the estrone binding site.


Adaptive array technique for differential-phase reflectometry in QUEST.
A Phased Array Antenna (PAA) was considered as launching and receiving antennae in reflectometry to attain good directivity in its applied microwave range. A well-focused beam was obtained in a launching antenna application, and differential-phase evolution was properly measured by using a metal reflector plate in the proof-of-principle experiment at low power test facilities. Differential-phase evolution was also evaluated by using the PAA in the Q-shu University Experiment with Steady State Spherical Tokamak (QUEST). A beam-forming technique was applied in receiving phased-array antenna measurements. In the QUEST device that should be considered as a large oversized cavity, standing wave effect was significantly observed with perturbed phase evolution. A new approach using derivative of measured field on propagating wavenumber was proposed to eliminate the standing wave effect.


Integration of an anti-tumor drug into nanocrystalline assemblies for sustained drug release.
Delicate mesoscopic architectures, bearing complex forms with multiple hierarchy levels, lead to significant functions in biogenic minerals. Herein, a bio-inspired approach was developed to fabricate comet-shaped assemblies of an anti-tumor drug - 10-hydroxycamptothecin (HCPT). The anti-solvent co-precipitation of HCPT and the excipient - PEG-b-PLGA - within the emulsifier leads to the immediate nucleation of comet bundles, followed by a secondary nucleation to generate the comet head, which is an assembly of nanofibers aligned almost in parallel. The continuous manufacturing furnishes drug-excipient hybrid particles with high drug-loading and a sustained drug release profile. This simple and efficient bio-inspired approach led to a promising sustained local drug delivery system, and could be extended to the fabrication of other functional organic materials bearing mesoscopic structural units.