Loss of set in muscle responses to limb perturbations during cerebellar dysfunction.
The properties of electromyograph (EMG) responses that enabled the arm to return accurately to target following limb perturbations were investigated in five Cebus monkeys. In particular, factors that affected the timing and magnitude of an early antagonist response that occurred prior to stretch of the antagonist muscle were examined. The early antagonist response was large and early (latency, 60 ms) when the perturbation was brief and a constant force assisted the return movement. In this situation, early contraction of the antagonist muscle was required to prevent the return movement from overshooting the target. To determine whether this early antagonist response was influenced by prior instruction (which in this case was the type of perturbation the monkey had previously received), two types of perturbations requiring different EMG responses were studied. When torque steps (duration, 2,000 ms) were expected and were applied, monkeys generated M1, M2, and M3 responses and later activity only in the agonist (the initially stretched) muscle. When torque pulses (duration, 40 ms) were expected and were applied, monkeys generated M1 and M2 responses in the agonist and an early antagonist response. EMG responses to torque pulses and steps were then compared when the type of perturbation was expected and when it was unexpected. These comparisons revealed that the early antagonist response only occurred when the monkey expected a torque pulse. Therefore, this response was dependent on set. Expectation of a torque step caused enhancement of the agonist M2 and M3 responses. These agonist and antagonist EMG responses that were dependent on set were also influenced by changes in afferent drive. Cerebellar nuclear cooling through probes implanted lateral and medial to the dentate abolished that component of EMG responses attributed to set. The residual EMG responses in agonists and antagonists appeared to be driven by stretch of their respective muscles. The results suggest that when the nature of an arm perturbation is correctly predicted, the cerebellum provides accuracy in repositioning the limb a) by adjusting the magnitude of the M2 agonist response and b) by enabling activity after a latency of 60 ms (e.g., the M3 and early antagonist response) to be switched to the agonist or antagonist as appropriate, irrespective of which muscle is being stretched. This latter mechanism provides the motor system with predictive ability.


Tetraiodothyroacetic acid-tagged liposomes for enhanced delivery of anticancer drug to tumor tissue via integrin receptor.
Nanoparticles have demonstrated potential for promoting drug delivery to tumor sites and enhancing uptake. Here, we report tetraiodothyroacetic acid (tetrac) as a promising new targeting moiety for delivery of anticancer drugs to tumor tissues. Tetrac, an antagonist that blocks the binding of thyroid hormone to integrin αvβ3, was covalently linked to the activated end of pegylated lipid and used to formulate tetrac-tagged pegylated liposomes (TPL). After incubating with TPL for 9h, cellular accumulation efficiency into A375 human melanoma cells, which express integrin αvβ3 at high density, was high (98.5%± 0.5% of cells), whereas that in KB cells, which express integrin at a very low density, was much lower (35.1%± 4.5%). Molecular imaging revealed that TPL preferentially distributed to tumor tissues after systemic administration in mice, where as non-targeting pegylated liposomes were distributed to tumors at background levels. Treatment with the alkyl lysophospholipid anticancer drug edelfosine, encapsulated in TPL, significantly reduced the survival of A375 tumor cells compared to cells treated with edelfosine in pegylated liposomes or with lysophosphatidylcholine encapsulated in TPL. Moreover, intravenous administration of edelfosine in TPL significantly reduced the growth of tumors and prolonged the survival of A375-xenografted mice, providing 100% protection for up to 50 days and some protection until 66 days (0% survival endpoint). In contrast, no untreated mice or mice treated with edelfosine-loaded pegylated liposomes survived up to 50 or 48 days, respectively, after tumor inoculation. These results suggest the potential of tetrac as a new ligand moiety for enhancing the delivery of anticancer drug-loaded nanoparticles to tumors and enhancing the therapeutic efficacy of encapsulated anticancer drugs.


Full spectrum of psychiatric disorders related to foreign migration: a Danish population-based cohort study.
Although increased risk for schizophrenia among immigrants is well established, knowledge of the broader spectrum of psychiatric disorders associated with a foreign migration background is lacking. To examine the full range of psychiatric disorders associated with any type of foreign migration background among persons residing in Denmark, including foreign-born adoptees, first- and second-generation immigrants, native Danes with a history of foreign residence, and persons born abroad to Danish expatriates. Danish population-based cohort study. Persons were followed up from their 10th birthday for the development of mental disorders based on outpatient and inpatient data. All persons born between January 1, 1971, and December 31, 2000 (N = 1 859 419) residing in Denmark by their 10th birthday with follow-up data to December 31, 2010. Incidence rate ratios (IRRs) and cumulative incidences for psychiatric outcomes. All categories of foreign migration background, except persons born abroad to Danish expatriates, were associated with increased risk for at least 1 psychiatric disorder. Foreign-born adoptees had increased IRRs for all psychiatric disorders and had the highest IRRs for these disorders compared with other foreign migration categories. First- and second-generation immigrants having 2 foreign-born parents had significantly increased IRRs for schizophrenia and schizophrenia spectrum disorders and had similar risk magnitudes. Second-generation immigrants having 1 foreign-born parent had significantly increased IRRs for all psychiatric disorders. Native Danes with a history of foreign residence had increased IRRs for bipolar affective disorder, affective disorders, personality disorders, and schizophrenia spectrum disorders. The extent to which a background of foreign migration confers an increased risk for the broad spectrum of psychiatric disorders varies according to parental origin, with greatest risks for foreign-born adoptees. The spectrum of psychiatric disorders showed greater variation within the second-generation immigrant group than between first-generation vs second-generation immigrants, and the spectrum differed according to whether individuals had 1 or 2 foreign-born parents.


The nonsurgical treatment of patients with periodontal disease: results after 6.4 years.
In a previous study involving patients at the dental clinic of the Detroit Receiving Hospital, 87% of teeth that initially had been recommended for surgery or extraction were spared either treatment through a combination of debridement and short-term usage of antimicrobial agents. The object of the present study was to determine what changes occurred to these teeth after 6.4 years in the maintenance phase of treatment. Patients were scheduled for maintenance therapy at three-month intervals over a period of 6.4 years. They were evaluated "annually" (that is, the patients were scheduled for annual visits) for surgical needs by a clinician who was not aware of the treatment received by the patients. Multivariate statistical models were used to determine which variables predicted subsequent surgical needs. The initial treatment benefits were sustained, as the majority of patients showed no increase in surgical needs after 6.4 years. When relapse occurred, those who were smoking when the study began and an increased number of sessions of debridement were predictors. Surgical needs were reduced when metronidazole was dispensed after the first and second annual examinations.


Familial aggregation of amyotrophic lateral sclerosis, dementia, and Parkinson's disease: evidence of shared genetic susceptibility.
Clinicians have long suspected an association of classic amyotrophic lateral sclerosis (ALS) with Parkinson's disease (PD), dementia, or both. If proven, this would raise the possibility of a shared genetic susceptibility to the three disorders. To investigate this hypothesis, we compared 151 newly diagnosed ALS patients (seven familial) with 140 controls in terms of cumulative incidence of ALS, PD, and dementia in parents, siblings, and grandparents. We used Cox proportional hazards analysis to compute rate ratios (RRs) for ALS, dementia, and PD in relatives of ALS patients versus relatives of controls. The risk for dementia was significantly higher in relatives of ALS patients than in those of controls (RR = 1.9; 95% CI 1.1-3.1) and was similar for relatives of patients with sporadic and familial ALS. The risk of PD was higher in relatives of patients with familial ALS (RR = 5.6; 95% CI 0.6-50.3) than in relatives of patients with sporadic ALS (RR = 1.8; 95% CI 0.5-6.0), but these differences were not statistically significant, probably due to insufficient statistical power with the available sample size. These findings indicate that ALS and dementia, and perhaps also PD, co-occur within families more often than expected by chance, suggesting that there may be a shared genetic susceptibility to these disorders.


Airflow rates and breathlessness recovery from submaximal exercise in healthy adults: prospective, randomised, cross-over study.
Facial airflow from a hand-held fan may reduce breathlessness severity and hasten postexertion recovery. Data from randomised controlled trials are limited and the optimal airflow speed remains unknown. We aimed to determine the effect of different airflow speeds on recovery from exercise-induced breathlessness. A prospective, randomised, cross-over design. Ten healthy participants (seven male; mean age 29±4 years; height 175±9 cm; body mass 76.9±14.1 kg) completed six bouts of 4 min of exercise. During the first 5 min of a 20 min recovery phase, participants received one of five airflow speeds by holding a fan ~15 cm from their face, or no fan control, administered in random order. Fan A had an internal blade, and fan B had an external blade. Breathlessness was measured using a numerical rating scale (NRS) at minute intervals for the first 10 min, and facial skin temperature was recorded using a thermal imaging camera (immediately postexertion and 5 min recovery). Nine participants completed the trial. A significant main effect for airflow speed (p=0.016, ηp2=0.285) and interaction effect for airflow speed over time (p=0.008, ηp2=0.167) suggest that the airflow speed modifies breathlessness during recovery from exercise. Fan speeds of 1.7 m/s or greater increased the speed of recovery from breathlessness compared with control (p<0.05) with the highest airflow speeds (2.5 m/s and 3.3 m/s) giving greatest facial cooling. Higher airflow rates (1.7 m/s or greater) reduced self-reported recovery times from exercise-induced breathlessness and reduced facial temperature .


Chromatin immunoprecipitation-mediated target identification proved aquaporin 5 is regulated directly by estrogen in the uterus.
Estrogens play a central role in the reproduction of vertebrates and affect a variety of biological processes. The major target molecules of estrogens are nuclear estrogen receptors (ERs), which have been studied extensively at the molecular level. In contrast, our knowledge of the genes that are regulated directly by ERs remains limited, especially at the level of the whole organism rather than cultured cells. In order to identify genes that are regulated directly by ERs in vivo, we used estrogen treated mouse uterus and performed chromatin immunoprecipitation. Sequence analysis of a precipitated DNA fragment enabled alignment with the mouse genomic sequence and revealed that the promoter region of the gene encoding aquaporin 5 (AQP5) was precipitated with antibody against ER alpha. Quantitative PCR and DNA microarray analyses confirmed that AQP5 is activated soon after administration of estrogen. In addition, the promoter region of AQP5 contained a functional estrogen response element that was activated directly by estrogen. Although several AQP genes are expressed in the uterus, only direct activation of AQP5 could be detected following treatment with estrogen. This chromatin immunoprecipitation-mediated target identification may be applicable to the study of other transcription factor networks.


A potent trypanocidal component from the fungus Lentinus strigosus inhibits trypanothione reductase and modulates PBMC proliferation.
The fungus Lentinus strigosus (Pegler 1983) (Polyporaceae, basidiomycete) was selected in a screen for inhibitory activity on Trypanosoma cruzi trypanothione reductase (TR). The crude extract of L. strigosus was able to completely inhibit TR at 20 microg/ml. Two triquinane sesquiterpenoids (dihydrohypnophilin and hypnophilin), in addition to two panepoxydol derivatives (neopanepoxydol and panepoxydone), were isolated using a bioassay-guided fractionation protocol. Hypnophilin and panepoxydone displayed IC50 values of 0.8 and 38.9 microM in the TR assay, respectively, while the other two compounds were inactive. The activity of hypnophilin was confirmed in a secondary assay with the intracellular amastigote forms of T. cruzi, in which it presented an IC50 value of 2.5 micro M. Quantitative flow cytometry experiments demonstrated that hypnophilin at 4 microM also reduced the proliferation of human peripheral blood monocluear cells (PBMC) stimulated with phytohemaglutinin, without any apparent interference on the viability of lymphocytes and monocytes. As the host immune response plays a pivotal role in the adverse events triggered by antigen release during treatment with trypanocidal drugs, the ability of hypnophilin to kill the intracellular forms of T. cruzi while modulating human PBMC proliferation suggests that this terpenoid may be a promising prototype for the development of new chemotherapeutical agents for Chagas disease.


Identification of Proteins Involved in Carbohydrate Metabolism and Energy Metabolism Pathways and Their Regulation of Cytoplasmic Male Sterility in Wheat.
Cytoplasmic male sterility (CMS) where no functional pollen is produced has important roles in wheat breeding. The anther is a unique organ for male gametogenesis and its abnormal development can cause male sterility. However, the mechanisms and regulatory networks related to plant male sterility are poorly understood. In this study, we conducted comparative analyses using isobaric tags for relative and absolute quantification (iTRAQ) of the pollen proteins in a CMS line and its wheat maintainer. Differentially abundant proteins (DAPs) were analyzed based on Gene Ontology classifications, metabolic pathways and transcriptional regulation networks using Blast2GO. We identified 5570 proteins based on 23,277 peptides, which matched with 73,688 spectra, including proteins in key pathways such as glyceraldehyde-3-phosphate dehydrogenase, pyruvate kinase and 6-phosphofructokinase 1 in the glycolysis pathway, isocitrate dehydrogenase and citrate synthase in the tricarboxylic acid cycle and nicotinamide adenine dinucleotide (NADH)-dehydrogenase and adenosine-triphosphate (ATP) synthases in the oxidative phosphorylation pathway. These proteins may comprise a network that regulates male sterility in wheat. Quantitative real time polymerase chain reaction (qRT-PCR) analysis, ATP assays and total sugar assays validated the iTRAQ results. These DAPs could be associated with abnormal pollen grain formation and male sterility. Our findings provide insights into the molecular mechanism related to male sterility in wheat.


Trial of labor after cesarean (TOLAC) in women with premature rupture of membranes.
Introduction: The aim of this study was to assess the success rate of a trial of labor after a previous cesarean section (TOLAC) in the settings of premature rupture of membranes (PROM) and to compare conservative management with spontaneous labor and induction of labor.Methods: This was a retrospective cohort study conducted in a single tertiary care center between January 2011 and March 2017. Women with singleton pregnancy and a previous cesarean section (CS) who presented with PROM and underwent TOLAC were included. Outcomes and rate of successful vaginal delivery after induction of labor were compared to conservative treatment and spontaneous labor.Results: Among 830 women who met the inclusion criteria, 723 (87.1%) had a spontaneous onset of labor following PROM and 107 (12.9%) had an induction of labor. The rate of successful TOLAC was similar between the groups (75.7 vs. 81.6%, respectively, p = .22). However, induction of labor was associated with an increased risk for uterine rupture (1.87 vs. 0.96%, p < .001), operative complications (6.7 vs. 2.3%, p < .001), and composite maternal postpartum complications (21.4 vs. 10.7%, respectively, p = .014) compared to conservative management with spontaneous initiation of labor. There was no difference in neonatal outcome between the groups.Conclusion: Induction of labor following PROM in women with a previous CS is associated with high successful vaginal delivery rate. However, the risk for uterine rupture and operative and maternal complications is significantly increased compared to spontaneous initiation of labor.


Identification of chilling stress-responsive tomato microRNAs and their target genes by high-throughput sequencing and degradome analysis.
MicroRNAs (miRNAs) are a class of noncoding small RNAs (sRNAs) that are 20-24 nucleotides (nt) in length. Extensive studies have indicated that miRNAs play versatile roles in plants, functioning in processes such as growth, development and stress responses. Chilling is a common abiotic stress that seriously affects plants growth and development. Recently, chilling-responsive miRNAs have been detected in several plant species. However, little is known about the miRNAs in the model plant tomato. 'LA1777' (Solanum habrochaites) has been shown to survive chilling stress due to its various characteristics. Here, two small RNA libraries and two degradome libraries were produced from chilling-treated (CT) and non-chilling-treated (NT) leaves of S. habrochaites seedlings. Following high-throughput sequencing and filtering, 161 conserved and 236 novel miRNAs were identified in the two libraries. Of these miRNAs, 192 increased in the response to chilling stress while 205 decreased. Furthermore, the target genes of the miRNAs were predicted using a degradome sequencing approach. It was found that 62 target genes were cleaved by 42 conserved miRNAs, while nine target genes were cleaved by nine novel miRNAs. Additionally, nine miRNAs and six target genes were validated by quantitative real-time PCR (qRT-PCR). Target gene functional analysis showed that most target genes played positive roles in the chilling response, primarily by regulating the expression of anti-stress proteins, antioxidant enzyme and genes involved in cell wall formation. Tomato is an important model plant for basic biological research. In this study, numerous conserved and novel miRNAs involved in the chilling response were identified using high-throughput sequencing, and the target genes were analyzed by degradome sequencing. The work helps identify chilling-responsive miRNAs in tomato and increases the number of identified miRNAs involved in chilling stress. Furthermore, the work provides a foundation for further study of the regulation of miRNAs in the plant response to chilling stress.


Understanding Consumer Interaction on Instagram: The Role of Satisfaction, Hedonism, and Content Characteristics.
The increasing relevance of Instagram and its growing adoption among top brands suggest an effort to better understand consumers' behaviors within this context. The purpose of this study is to examine the role of perceived hedonism and satisfaction in determining consumers' intentions to interact and their actual interaction behaviors (the number of likes, by tapping a heart icon, and comments) in a brand's official Instagram account. Also, we investigate the effect of consumer perceptions about the characteristics of the content generated in the account (perceived originality, quantity, and quality) on their perceived hedonism and satisfaction. Data were collected in two stages from 808 members of a fashion brand's official Instagram account. First, participants answered an online questionnaire to evaluate their perceptions, satisfaction, and interaction intentions. Second, 1 month later, we measure the number of likes and comments done by each participant in the brand's official Instagram account during that month. Using partial least squares to analyze the data, perceived hedonism is found to affect both satisfaction and the intention to interact in Instagram, which in turn influences actual behavior. Besides, perceived originality is the most relevant content characteristic to develop perceived hedonism. These findings offer managers a general vision of consumers' behaviors on Instagram, highlighting the importance of hedonism to create a satisfactory experience.


Lysine 84 is at the subunit interface of lac repressor protein.
Mutations have been generated at the Lys84 site of the lac repressor to explore its predicted role in inducer binding and/or subunit interaction. Four single mutations, Lys84-->Ala, Lys84-->Leu, Lys84-->Arg, and Lys84-->Glu, have been generated by site-specific mutagenesis. In addition, the mutation Tyr282-->Asp, which results in a monomeric repressor, has been coupled with these four single mutants to generate the four corresponding double mutants. Unchanged inducer binding affinities in all Lys84 mutants except Lys84-->Arg suggest that Lys84 does not contribute energy to inducer binding and is not found in the inducer-binding site as previously proposed (Sams, C. F., Vyas, N. K., Quiocho, F. A., and Matthews, K. S. (1984) Nature 310, 429-430). Interestingly, the double mutants with hydrophobic side chains at the Lys84 site are tetramers, while those with charged side chains remain monomers. This result agrees with the recent model of the lac repressor (Nichols, J. C., Vyas, N. K., Quiocho, F. A., and Matthews, K. S. (1993) J. Biol. Chem. 268, 17602-17612), in which Lys84 is mapped by sequence alignment to the same face of the subunit as Tyr282. More detailed inducer binding, operator binding, and immunoblotting studies show that all the mutations at Lys84 have quaternary structures that deviate from wild-type protein, providing supportive evidence for the model placing this residue on the surface of the monomer subunit. Substitution of Lys84 by Ala or Leu results in 100-200-fold decreased association and dissociation rate constants for inducer binding and biphasic character. This decrease can be rescued at least partially in the respective double mutants at elevated pH, at which wild-type repressor shows a 10-fold decrease in affinity and cooperativity in inducer binding. In all substitutions with Ala or Leu, immunoblotting patterns with monoclonal antibody, an assay sensitive to alterations in quaternary structure, are distinct from wild-type repressor. Although substitution with Arg at position 84 yields a protein with 10-fold lower inducer binding affinity, the mutant shows decreased pH dependence of inducer binding. Substitution at this site with Glu results in cooperativity at neutral pH with no change in inducer binding at elevated pH. In addition, operator binding affinity of this mutant is affected by elevated pH, a phenomenon not observed in wild-type repressor. These changes in inducer and operator binding properties appear to be related to the altered quaternary structure of these mutants at Lys84.


Equilibrium isotherms, kinetics, and thermodynamics studies for congo red adsorption using calcium alginate beads impregnated with nano-goethite.
The present study is concerned with the batch adsorption of congo red (CR) from an aqueous solution using calcium alginate beads impregnated with nano-goethite (CABI nano-goethite) as an adsorbent. The optimum conditions for CR removal were determined by studying operational variables viz. pH, adsorbent dose, contact time, initial dye ion concentration and temperature. The CABI nano-goethite was characterized by Fourier transform infrared spectroscopy (FTIR), X- ray diffraction (XRD) and Scanning electron microscopy/energy dispersive spectroscopy (SEM/EDS) analysis. The CR sorption data onto CABI nano-goethite were described using Langmuir, Freundlich, Dubinin-Radushkevich and Temkin isotherm models. The results show that the best fit was achieved with the Langmuir isotherm model. The maximum adsorption capacity (181.1mg/g) of CR was occurred at pH 3.0. Kinetic studies showed that the adsorption followed a pseudo-second-order model. Desorption experiments were carried out to explore the feasibility of regenerating the adsorbent and the adsorbed CR from CABI nano-goethite. The best desorbing agent was 0.1M NaOH with an efficiency of 94% recovery. The thermodynamic parameters ΔG°, ΔH°, and ΔS° for the CR adsorption were determined by using adsorption capacities at five different temperatures (293, 303, 313, 323 and 303K). Results show that the adsorption process was endothermic and favoured at high temperature.


Lensless optical data hiding system based on phase encoding algorithm in the Fresnel domain.
A novel and efficient algorithm based on a modified Gerchberg-Saxton algorithm (MGSA) in the Fresnel domain is presented, together with mathematical derivation, and two pure phase-only masks (POMs) are generated. The algorithm's application to data hiding is demonstrated by a simulation procedure, in which a hidden image/logo is encoded into phase forms. A hidden image/logo can be extracted by the proposed high-performance lensless optical data-hiding system. The reconstructed image shows good quality and the errors are close to zero. In addition, the robustness of our data-hiding technique is illustrated by simulation results. The position coordinates of the POMs as well as the wavelength are used as secure keys that can ensure sufficient information security and robustness. The main advantages of this proposed watermarking system are that it uses fewer iterative processes to produce the masks, and the image-hiding scheme is straightforward.


Severe Acute Respiratory Syndrome Coronavirus 2 Vaccines: A Historical Viral Vaccine Perspective.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are a remarkable scientific achievement. The perspective on past viral vaccine performance and viral characteristics, such as incubation period, can help with messaging and instilling vaccine confidence. Protection against mild infection occurs in the short term (months), but the persistence of protection against severe disease will likely endure longer.


Combination of parity and pre-pregnancy BMI and low birth weight infants among Japanese women of reproductive age.
This study aimed to examine the effects of parity and pre-pregnancy body mass index (BMI) on low birth weight (LBW) infants among Japanese women. Participants included 1,518 mothers (mean age 34.0 years) of singleton full-term infants in 2011. The incidence of LBW infants was 7.5% in primiparous women with BMI<18.5 (Group A; n=239), 4.0% in multiparous women with BMI<18.5 (Group B; n=124), 6.0% in primiparous women with 18.5≤BMI<25 (Group C; n=715), and 1.8% in multiparous women with 18.5≤BMI<25 (Group D; n=440). A multivariable logistic regression model revealed that mothers in Group A were more likely to deliver a LBW infant [odds ratio (OR) 6.41, 95% confidence interval (CI), 2.65-15.49] than were mothers in Group D. Being both underweight (OR 1.8, 95% CI: 1.05-3.11) and primiparous (OR 3.41, 95% CI: 1.82-6.44) were independently associated with LBW infants. This study demonstrated that the characteristics of primiparous and underweight in mothers are additively associated with LBW infants.


Drug use and harm reduction in Afghanistan.
Opium has been cultivated in Afghanistan since 1100 A.D., although production has steadily increased since 1979. Currently, Afghanistan produces three-quarters of the global opium supply, with injection drug use and HIV currently following the opium trade route through Central Asia. Although systematic studies are lacking, heroin use appears to be on the rise in Afghanistan. The purpose of this paper is to briefly provide historical background and current statistics for drug production and use in Afghanistan, to discuss the new government's policies towards problem drug use and available rehabilitation programs, and to assess Afghan harm reduction needs with consideration of regional trends.


The development of radiotherapy: physics, technology methods.
Radiotherapy was introduced in Sweden already before the turn of the century, ie, a few years after the discovery of x-rays and radioactivity. Pioneering contributions were made by Forssell, Berven, Heyman, Sievert, and Strandqvist in general radiotherapy, gynecologic radiotherapy, dosimetry, teleradium methods, and radiation biology. Technological advancements, along with nearly 100% followup of treatment effects, created a foundation for compiling early empirical experience in a methodologically sound specialty. Therapeutic radiology in Sweden was distinguished from diagnostic radiology already in 1917, at which time the specialties of general and gynecologic radiotherapy were founded. These specialties later developed into general and gynecologic oncology. Progress during recent decades has been characterized by access to better equipment such as telegamma devices and accelerators for external radiotherapy, and new radionuclides, eg, for remote controlled local application. With CT (computed tomography) and MRI (magnetic resonance imaging), SPECT and PET (tomography using gamma radiation and positron-irradiated nuclides), and ultrasound diagnostics, the anatomic basis for individual dose planning has radically improved. Dosage can now be planned with high precision and visualized in three dimensions using advanced computer programs. Technical safety has increased with improved methods for in vivo dosimetry and computer-controlled verification of all parameters for every treatment. It is now possible to deliver the intended radiation dose to a benign tumor without causing serious side effects. Important research fields include the impact of different fractionation schedules on the effects of radiation and how radiotherapy can best be combined with other forms of therapy such as surgery and chemotherapy.


Oral Multimodal Analgesia for Total Joint Arthroplasty.
Oral multimodal analgesia for hip and knee arthroplasty is increasingly used as part of enhanced recovery protocols designed to minimize early postoperative pain and to facilitate early discharge, while minimizing undesirable side effects related to single-agent opioid administration. This article is a review of previously published data evaluating the use of various oral medications in the management of postoperative pain after lower extremity arthroplasty and was presented as part of a symposium at the November 2016 AAHKS Annual Meeting. Multimodal analgesia has been shown to reduce opioid consumption and side effects, with a positive effect on both early and longer term outcomes for hip and knee arthroplasty patients. Medications directed at multiple points on the pain cascade minimize pain by different mechanisms. Suggested dosing regimens are proposed. Oral multimodal analgesia incorporating a combination of opioid and nonopioid analgesics, selective and nonselective anti-inflammatory drugs, acetaminophen, and gabapentinoids are recommended as a part of a pre-emptive approach to pain management in patients undergoing hip or knee arthroplasty. Reduction of opioid consumption and minimization of side effects are primary outcomes, and prevention of chronic pain can positively affect long-term results.


The p38 mitogen-activated protein kinase signaling pathway is coupled to Toll-like receptor 5 to mediate gene regulation in response to Pseudomonas aeruginosa infection in human airway epithelial cells.
In this study, we show that stimulation of human airway epithelial cells (HAECs) by Pseudomonas aeruginosa strain PAO1 induces time- and dose-dependent activation of p38 mitogen-activated protein kinase (MAPK). Activated p38 MAPK stayed in the cytoplasm instead of translocating to the nucleus, as shown by cellular fractionation. p38 MAPK was activated when HAECs were incubated with P. aeruginosa strain PAK and Burkholderia cepacia, while little activation was observed with the isogenic flagellin-free strains PAK/fliC and B. cepacia BC/fliC. The presence of Toll-like receptor 5 (TLR5) in 293 cells mediated PAO1-dependent activation of p38 MAPK, and in HAECs p38 MAPK activation was blocked by the overexpression of a dominant negative TLR5. Two inhibitors of p38 MAPK, SB202190 and SB203580, significantly attenuated PAO1-dependent expression of an NF-kappaB-dependent luciferase reporter gene, suggesting that p38 MAPK activation is required for full activation of NF-kappaB-dependent signaling. Microarray analysis of NF-kappaB target genes revealed up-regulation of multiple genes by PAO1 in HAECs. Reverse transcription-PCR and protein expression analysis were used to show that up-regulation of NF-kappaB-dependent genes induced by PAO1, such as the genes encoding Cox-2 and interleukin-8, was attenuated by SB203580. These results demonstrate a role for p38 MAPK signaling in gene regulation in response to P. aeruginosa via TLR5.


Primers are decisive for sensitivity of PCR.
A sufficient sensitivity of PCR is a prerequisite for its use in the diagnosis of infectious diseases. We have used PCR for detecting gene elements of Borrelia burgdorferi, mycobacteria and Bordetella pertussis. With all these microbe groups, difficulties were encountered in achieving the demanded sensitivity with the primer pairs primarily selected. An extensive testing of various reaction parameters did not improve the sensitivity. Subsequently, we synthesized more primers derived from slightly different positions of the original target sequences. When the original and new primers were tested in possible combinations, some primer pairs reached 100-fold to 1000-fold higher sensitivity than the primary pairs. We conclude that in optimizing the sensitivity of PCR, more emphasis should be put on testing of several primer pairs than on the extensive screening of reaction parameters. Thus far, a trial-and-error approach has to be used, because there is no means to predict the sensitivity properties of a selected primer pair.


Production of ochratoxin A by Aspergillus ochraceus NRRL-3174 before and after exposures to 60Co irradiation.
Spores from the toxigenic organism Aspergillus ochraceus NRRL-3174 were exposed to specific levels of gamma irradiation and then allowed to germinate on selected media. Increases in ochratoxin A production by irradiated, compared to non-irradiated, spores were observed after inoculation of spores onto a cracked red wheat or into a synthetic liquid medium. Variations in daily ochratoxin production were also observed for control and irradiated spore-derived cultures developing on both media, with maximum toxin production varying from 7 to 11 days of incubation. The most notable increases in ochratoxin A production occurred from cultures developing from spores having been irradiated with 10, 25, or 50 krad. Exposures to 400 or 600 krad resulted in complete inhibition of spore germination and, consequently, no ochratoxin production. Of the two substrates used, wheat and synthetic, the quantities of ochratoxin A produced were significantly lower in the synthetic media than on the natural substrate. Higher and more rapid toxin production occurred from spores having been irradiated with 10, 25, 50, and 100 krad than occurred from the non-irradiated control spores when grown on synthetic media. Cultures derived from spores having been exposed to 10, 25, 50, and 100 krad produced significantly higher levels of ochratoxin A after 8 days of incubation on natural substrate than did the controls. Analysis of variance revealed that substrate, length of incubation, as well as irradiation levels all affected the time required to produce maximum levels of ochratoxin A.


Salinity impacts on water solubility and n-octanol/water partition coefficients of selected pesticides and oil constituents.
Salinity has been reported to influence the water solubility of organic chemicals entering marine ecosystems. However, limited data are available on salinity impacts for chemicals potentially entering seawater. Impacts on water solubility would correspondingly impact chemical sorption as well as overall bioavailability and exposure estimates used in the regulatory assessment. The pesticides atrazine, fipronil, bifenthrin, and cypermethrin, as well as the crude oil constituent dibenzothiophene together with 3 of its alkyl derivatives, all have different polarities and were selected as model compounds to demonstrate the impact of salinity on their solubility and partitioning behavior. The n-octanol/water partition coefficient (KOW ) was measured in both distilled-deionized water and artificial seawater (3.2%). All compounds had diminished solubility and increased KOW values in artificial seawater compared with distilled-deionized water. A linear correlation curve estimated salinity may increase the log KOW value by 2.6%/1 log unit increase in distilled water (R2 = 0.97). Salinity appears to generally decrease the water solubility and increase the partitioning potential. Environmental fate estimates based on these parameters indicate elevated chemical sorption to sediment, overall bioavailability, and toxicity in artificial seawater. These dramatic differences suggest that salinity should be taken into account when exposure estimates are made for marine organisms. Environ Toxicol Chem 2017;36:2274-2280. © 2017 SETAC.


[Heavy metal stabilization in municipal solid waste incineration fly ash using soluble phosphate].
The physico-chemical characteristics of municipal solid waste incineration fly ashes was analyzed. It indicated that the main elements of fly ashes are Ca, Cl, K, S and Si, and many heavy metals such as Pb, Zn, Cu, Mn and Cr can be found in fly ashes, and the heavy metal leaching toxicity such as Pb, Cu, Zn and Cd is much higher than the standards. A new kind of stabilization agent-soluble phosphate is chosen to treat with fly ash, different influence factors including agent dosage, curing time and pH are taken into consideration to test its stabilization for the stabilized fly ash. The experimental results indicate that fly ash treated with soluble phosphate can have excellent stabilization effect, and the leaching toxicity for Pb, Cd and Zn can be reduced by 97.5%, 91.6% and 95.5% at a phosphate dosage of 3%; curing time can not influence its stabilization; and, stabilized fly ash using soluble phosphate can keep long-term stabilization at a broad pH value.


Genome-wide SNP data suggest complex ancestry of sympatric North Pacific killer whale ecotypes.
Three ecotypes of killer whale occur in partial sympatry in the North Pacific. Individuals assortatively mate within the same ecotype, resulting in correlated ecological and genetic differentiation. A key question is whether this pattern of evolutionary divergence is an example of incipient sympatric speciation from a single panmictic ancestral population, or whether sympatry could have resulted from multiple colonisations of the North Pacific and secondary contact between ecotypes. Here, we infer multilocus coalescent trees from >1000 nuclear single-nucleotide polymorphisms (SNPs) and find evidence of incomplete lineage sorting so that the genealogies of SNPs do not all conform to a single topology. To disentangle whether uncertainty in the phylogenetic inference of the relationships among ecotypes could also result from ancestral admixture events we reconstructed the relationship among the ecotypes as an admixture graph and estimated f4-statistics using TreeMix. The results were consistent with episodes of admixture between two of the North Pacific ecotypes and the two outgroups (populations from the Southern Ocean and the North Atlantic). Gene flow may have occurred via unsampled 'ghost' populations rather than directly between the populations sampled here. Our results indicate that because of ancestral admixture events and incomplete lineage sorting, a single bifurcating tree does not fully describe the relationship among these populations. The data are therefore most consistent with the genomic variation among North Pacific killer whale ecotypes resulting from multiple colonisation events, and secondary contact may have facilitated evolutionary divergence. Thus, the present-day populations of North Pacific killer whale ecotypes have a complex ancestry, confounding the tree-based inference of ancestral geography.


Molecular and Functional Characteristics of DNA Polymerase Beta-Like Enzymes From Trypanosomatids.
Trypanosomatids are a group of primitive unicellular eukaryotes that can cause diseases in plants, insects, animals, and humans. Kinetoplast genome integrity is key to trypanosomatid cell survival and viability. Kinetoplast DNA (kDNA) is usually under attack by reactive oxygen and nitric species (ROS and RNS), damaging the DNA, and the cells must remove and repair those oxidatively generated lesions in order to survive and proliferate. Base excision repair (BER) is a well-conserved pathway for DNA repair after base damage, single-base loss, and single-strand breaks, which can arise from ROS, RSN, environmental genotoxic agents, and UV irradiation. A powerful BER system has been described in the T. cruzi kinetoplast and it is mainly carried out by DNA polymerase β (pol β) and DNA polymerase β-PAK (pol β-PAK), which are kinetoplast-located in T. cruzi as well as in other trypanosomatids. Both pol β and pol β-PAK belong to the X-family of DNA polymerases (pol X family), perform BER in trypanosomatids, and display intrinsic 5-deoxyribose phosphate (dRP) lyase and DNA polymerase activities. However, only Pol β-PAK is able to carry out trans-lesion synthesis (TLS) across 8oxoG lesions. T. cruzi cells overexpressing pol β are more resistant to ROS and are also more efficient to repair 8oxoG compared to control cells. Pol β seems to play a role in kDNA replication, since it associates with kinetoplast antipodal sites in those development stages in trypanosomatids which are competent for cell replication. ROS treatment of cells induces the overexpression of pol β, indicating that plays a role in kDNA repair. In this review, we will summarize the main features of trypanosomatid minicircle kDNA replication and the biochemical characteristics of pol β-like enzymes and their involvement in BER and kDNA replication. We also summarize key structural features of trypanosomatid pol β compared to their mammalian (human) counterpart.


Reciprocal activation between IL-6/STAT3 and NOX4/Akt signalings promotes proliferation and survival of non-small cell lung cancer cells.
Inflammatory cytokines and oxidative stress are two critical mediators in inflammation-associated cancer. Interleukin-6 (IL-6) is one of the most critical tumor-promoting cytokines in non-small cell lung cancer (NSCLC). In our recent study, we confirmed that NADPH oxidase 4 (NOX4), an important source of reactive oxygen species (ROS) production in NSCLC cells, promotes malignant progression of NSCLC. However, whether the crosstalk of NOX4 and IL-6 signalings exists in NSCLC remains undentified. In this study, we show that NOX4 expression is positively correlated with IL-6 expression in NSCLC tissues. Exogenous IL-6 treatment significantly enhances NOX4/ROS/Akt signaling in NSCLC cells. NOX4 also enhances IL-6 production and activates IL-6/STAT3 signaling in NSCLC cells. Specifically, NOX4 is confirmed to functionally interplay with IL-6 to promote NSCLC cell proliferation and survival. The in vivo results were similar to those obtained in vitro. These data indicate a novel NOX4-dependent link among IL-6 in the NSCLC microenvironment, oxidative stress in NSCLC cells and autocrined IL-6 in NSCLC cells. NOX4/Akt and IL-6/STAT3 signalings can reciprocally and positively regulate each other, leading to enhanced NSCLC cell proliferation and survival. Therefore, NOX4 may serve as a promising target against NSCLC alone with IL-6 signaling.


Loss of dipeptidylpeptidase IV activity in chronic rhinosinusitis contributes to the neurogenic inflammation induced by substance P in the nasal mucosa.
In this study, we have found that dipeptidylpeptidase IV (DPPIV) plays in vivo an active role in the modulation of the inflammatory response of chronic rhinosinusitis. Human nasal mucosa expresses DPPIV-like immunoreactivity in submucosal seromucus glands, leukocytes, and endothelial cells of blood vessels. DPPIV enzymatic activity in nasal tissue biopsies taken from patients suffering from chronic rhinosinusitis was correlated inversely with the density of inflammatory cells in the nasal mucosa, and the DPPIV activity rose when chronic rhinosinusitis was treated. By using a pig animal model, we have shown that the intranasal administration of recombinant DPPIV decreased the vasodilatation induced by exogenous substance P (SP), a proinflammatory peptide released by sensory nerves. In contrast, an inhibitor of DPPIV enhanced the vasodilatatory effect at low doses of SP. SP5-11 was 100- to 1000-fold less potent than SP as a vasodilator of the nasal mucosa. The vasodilatatory effect of SP was abolished by a NK1 receptor antagonist. In conclusion, these results suggest a new pathophysiological pathway for rhinitis based on clinical observations in humans, indicating the involvement of an enzyme to modulate non-adrenergic and non-cholinergic substrate that occurred during nasal dysfunctions.


[The primordial genesis of psyche: emergence and formalization].
Although there is no doubt that life was preceded by a purely physical universe from which it emerged, still there are some conceptual blanks which are necessary to analyse in order to make intelligible not only the evolutional origin of sensibility, perception and conscience but also its settlement in the process of evolution and the contribution of psychicsm to the efficiency of organisms as tele-onomical systems. Nowadays science considers that this happens because of a continuous emergence of novelty in organisms with a more and more developed and complex nervous system, which facilitates actions of adaptation seeking optimal survival. According to Zubiri, the basque thinker who we intend to analyse here, the humanization springs up from potentiality of matter, through a process of transformation, systematization and elevation. Intelligence emerges as a result of biological hyper-formalization so that man can survive taking over reality. If this function is increased, it will give richness to psychic life and, as this is a changeable activity, it can admit enlargements, retractions and internal modifications.


Thyroid gland tuberculosis with endolaryngeal extension: a case with laryngotracheal dyspnoea.
Tuberculosis affecting the thyroid gland is a rare condition. We present the case of a 30-year-old man with thyroid tuberculosis whose presenting complaints were dyspnoea and hoarseness. There was a cystic mass in the posterosuperior right thyroid lobe extending into the paraglottic space. There was also recurrent laryngeal nerve involvement. We performed surgery and administered post-operative antituberculous treatment.


The Fungicidal Activity of Tebuconazole Enantiomers against Fusarium graminearum and Its Selective Effect on DON Production under Different Conditions.
Tebuconazole, which consists of a pair of enantiomers with different fungicidal activities, is one of the most common fungicides used in the control of Fusarium graminearum. In this study, the fungicidal activity of rac-tebuconazole and its enantiomers against F. graminearum was determined at 0.997, 0.975, and 0.950 aw and at 20, 25, and 30 °C on wheat-based media. Then, F. graminearum was treated with rac-tebuconazole and its enantiomers at the EC10, EC50, and EC90 levels under different culture conditions, and DON production was measured. Finally, expression of the DON biosynthetic genes ( TRI5 and TRI6) was quantified by real-time RT-PCR after incubation with EC50 doses of rac-tebuconazole and its enantiomers for 4, 8, and 14 days at 30 °C and aw 0.997. The results showed that the fungicidal activity of tebuconazole was strongly influenced by temperature, aw, and the combined factors. (-)-Tebuconazole is higher in fungicidal activity than (+)-tebuconazole and rac-tebuconazole with 24-99-fold and 1.8-6.7-fold, respectively. However, (-)-tebuconazole was generally more favorable for DON production than (+)-tebuconazole under the same conditions. Additionally, (-)-tebuconazole and rac-tebuconazole induced significantly increased expression of the DON biosynthetic genes ( TRI5 and TRI6) compared to the control by the 14th day of treatment. In this research, the combination condition of 30 °C and 0.997 aw is the most suitable for DON production by F. graminearum. The test strains of F. graminearum treated with the EC10 dose of (-)-tebuconazole produced the greatest amounts of DON.


Extremize Optical Chiralities through Polarization Singularities.
Chiral optical effects are generally quantified along some specific incident directions of exciting waves (especially for extrinsic chiralities of achiral structures) or defined as direction-independent properties by averaging the responses among all structure orientations. Though of great significance for various applications, chirality extremization (maximized or minimized) with respect to incident directions or structure orientations has not been explored, especially in a systematic manner. In this study we examine the chiral responses of open photonic structures from perspectives of quasinormal modes and polarization singularities of their far-field radiations. The nontrivial topology of the momentum sphere secures the existence of generic singularity directions along which mode radiations are either circularly or linearly polarized. When plane waves are incident along those directions, the reciprocity ensures ideal maximization and minimization of optical chiralities, for corresponding mode radiations of circular and linear polarizations, respectively. For directions of general elliptical polarizations, we have unveiled the subtle equality of a Stokes parameter and the circular dichroism, showing that an intrinsically (geometrically) chiral structure can unexpectedly exhibit no optical chirality at all or even optical chiralities of opposite handedness for different incident directions. The framework we establish can be applied to not only finite scattering bodies but also infinite structures, encompassing both intrinsic and extrinsic optical chiralities. We have effectively merged two vibrant disciplines of chiral and singular optics, which can potentially trigger more optical chirality-singularity related interdisciplinary studies.


Powder and Powder-Free Intra-Oral Scanners: Digital Impression Accuracy.
The purpose of this study was to evaluate the accuracy of digital impressions taken with two different intra-oral scanners (with and without optical powder), by dentists with different level of experience. Two intra-oral scanning devices (Apollo DI and Cerec Omnicam, Sirona Dental GmbH, Germany) were used to obtain a digital cast from scanning different preparations on a maxillary typodont. Three operator groups scanned five crown preparations using both powder and powder-free scanning systems. One group consisted of fourth year dental students, a second group consisted of prosthodontic residents, and third group consisted of prosthodontic specialists. The precision of spray application and impression expertise was compared between the three groups. The most frequently encountered errors were non-linear powder application, inappropriate intra-oral scanner manipulation, and insufficient digital data for crown fabrication. Experience is needed in order to achieve high quality digital impressions. A prosthodontic specialist avoided incorrect manipulation of an intra-oral camera, uneven application of powder spray and achieved a better marginal fit.


When Weaker Can Be Tougher: The Role of Oxidation State (I) in P- vs N-Ligand-Derived Ni-Catalyzed Trifluoromethylthiolation of Aryl Halides.
The direct introduction of the valuable SCF3 moiety into organic molecules has received considerable attention. While it can be achieved successfully for aryl chlorides under catalysis with Ni0(cod)2 and dppf, this report investigates the Ni-catalyzed functionalization of the seemingly more reactive aryl halides ArI and ArBr. Counterintuitively, the observed conversion triggered by dppf/Ni0 is ArCl > ArBr > ArI, at odds with bond strength preferences. By a combined computational and experimental approach, the origin of this was identified to be due to the formation of (dppf)NiI, which favors β-F elimination as a competing pathway over the productive cross-coupling, ultimately generating the inactive complex (dppf)Ni(SCF2) as a catalysis dead end. The complexes (dppf)NiI-Br and (dppf)NiI-I were isolated and resolved by X-ray crystallography. Their formation was found to be consistent with a ligand-exchange-induced comproportionation mechanism. In stark contrast to these phosphine-derived Ni complexes, the corresponding nitrogen-ligand-derived species were found to be likely competent catalysts in oxidation state I. Our computational studies of N-ligand derived NiI complexes fully support productive NiI/NiIII catalysis, as the competing β-F elimination is disfavored. Moreover, N-derived NiI complexes are predicted to be more reactive than their Ni0 counterparts in catalysis. These data showcase fundamentally different roles of NiI in carbon-heteroatom bond formation depending on the ligand sphere.


[Social development and family composition (author's transl)].
Starting from the theory regarding the social behaviour of the child and, on the other hand, from the concept of the family as a cultural and psychological and, in addition, sociological unit, an index of social development for children of 6 to 14 years of age is presented, and which is obtained by adding the process of school adaptation plus the process of learning plus personal attitudes. Having this hypothesis as a working basis, a study has been carried out on a total of 240 pupils (120 males and 120 girls) included in the chronological age of from 6 to 14 and belonging to National Schools in Zaragoza (Spain) and within the on going program of growth and development. Social development has been studied through inquiries of personal application at family level and through the application of psychograms of our own tabulation. The number of children in the family has been related to the aforementioned parameters, five family units having been established: one child, two children, three children, four children, five or more children. The overall result indicates that the index of social development proposed by us is higher in the case of unique children; that it is practically the same for those children whose family unit is of two, three or four children, and is sensibly lesser in children included in the family unit of five or more children.


Clinico-epidemiologic features of granuloma inguinale in the era of acquired immune deficiency syndrome.
Granuloma Inguinale (GI) is an endemic sexually transmitted disease (STD) in India. With increasing prevalence of human immunodeficiency virus (HIV) among patients with STD at a clinic in Mumbai, a study was conducted to determine clinico-epidemiologic features of GI and HIV. To determine possible interaction between GI and HIV. Prospective follow-up of 21 consecutive cases (GI in HIV-seropositive individuals) and 29 controls (GI in HIV-seronegative individuals) to determine time to heal. All cases and controls received a standard treatment regimen of erythromycin, 2 g po daily, under supervision until healing occurred. Although GI ulcers at recruitment were not significantly larger among HIV-seropositive individuals as compared with those seen among HIV-seronegative individuals (mean size 4.4 cm2 vs. 3.6 sq2; odds ratio [OR] 1.22, confidence interval [CI] .95, 0.63, 2.40; p = 0.52), the former took longer time to heal completely (mean 25.7 days vs. 16.8 days; OR 1.82, CI .95, 0.99, 3.36; p = 0.03) and tended to produce greater tissue destruction (as included in results). These findings are important because slow-healing GI ulcers with underlying HIV infection, which may be caused by their interaction, will lead to increased transmission of both the infections.


[Hyperthyroidism].
Although the classical presentation of hyperthyroidism is known from the nineteenth century, the mindful evaluation of the clinical symptoms is indispensable for the practitioner physician. The clinical picture depends on the etiology of hyperthyroidism, the gender and age of the patient. The methods for the laboratory diagnosis of hyperthyroidism have outstanding accuracy, the supersensitive TSH, free thyroxine and triiodothyronine determinations are generally available. The etiology of hyperthyroidism was broadened by new diseases: gestational hyperthyroidism caused by human choriogonadotropin and the group of congenital non-autoimmune hyperthyroidism due to TSH receptor mutations were discovered. The iodine-induced hyperthyroidism, which is an everyday problem due to the widespread use of amiodarone treatment, is also better characterized. The role of different treatment modalities in the therapeutic algorithm was established, the part of surgery decreased. The optimal duration and dose of drug treatment in Graves' disease is still questionable in the lack of good evidence, nowadays one and half year of antithyroid treatment is generally recommended. The reduction of relapse rate below 50% after the discontinuation of antithyroid drug was unsuccessful, risk factors are the large goiter, elevated level of the TSH receptor antibodies, in certain studies the male gender and young age. Due to the high relapse rate, the radioiodine treatment is preferred, even as a primary therapy. In case of toxic adenoma, toxic multinodular goiter and congenital non-autoimmune hyperthyroidism the medical treatment cannot result in permanent cure, therefore primary ablative treatment is required. The chances of patients with hyperthyroidism for the complete recovery are excellent, however, long time follow-up is necessary.


Where's Waldo? A new commensal species, Waldo arthuri (Mollusca, Bivalvia, Galeommatidae), from the Northeastern Pacific Ocean.
A galeommatid bivalve mollusk, representing a new species, is described from off the coasts of California and Vancouver Island, British Columbia. The new bivalve has a commensal relationship with the heart urchin, Brisaster latifrons. It has been observed crawling between the oral spines of this urchin, frequently near the peristome. The bivalve has been recorded from 80 (Vancouver Island) to 444 (southern California) meters depth, in muddy sediments. In common with other galeommatoideans, the new species broods its young; however it differs from the large majority of commensal members in lacking planktotrophic larval development. Waldo arthuri, new species, has multiple morphological, ecological and developmental similarities to other members of the genus Waldo Nicol, 1966, from the southern Atlantic and Antarctic Oceans. This is most pronounced for the Argentine species, Waldo paucitentaculatus Zelaya & Ituarte, 2013, Waldo arthuri's sister speciesin nuclear and mitochondrial gene trees. Despite this close relationship, Waldo arthuri is phylogentically distinct and possesses several hinge, shell sculpture, foot, and mantle tentacle characteristics that merit its description as new.


Exploring the Synergies of Single-Molecule Fluorescence and 2D Materials Coupled by DNA.
The world of 2D materials is steadily growing, with numerous researchers attempting to discover, elucidate, and exploit their properties. Approaches relying on the detection of single fluorescent molecules offer a set of advantages, for instance, high sensitivity and specificity, that allow the drawing of conclusions with unprecedented precision. Herein, it is argued how the study of 2D materials benefits from fluorescence-based single-molecule modalities, and vice versa. A special focus is placed on DNA, serving as a versatile adaptor when anchoring single dye molecules to 2D materials. The existing literature on the fruitful combination of the two fields is reviewed, and an outlook on the additional synergies that can be created between them provided.


Involvement of the PI3K/Akt/NF-κB Signaling Pathway in the Attenuation of Severe Acute Pancreatitis-Associated Acute Lung Injury by Sedum sarmentosum Bunge Extract.
Sedum sarmentosum Bunge possesses excellent anti-inflammatory properties and was used in the treatment of inflammatory diseases. The aim of the present study was to investigate the efficiency of Sedum sarmentosum Bunge extract (SSBE) on severe acute pancreatitis-associated (SAP-associated) acute lung injury (ALI) in rats and to explore the underlying mechanisms. Here, we used a sodium taurocholate-induced SAP rat model to determine the role of SSBE in ALI. During the course of pancreatitis, the expressions of phosphorylated phosphoinositide 3-kinases (PI3K)/protein kinase B (Akt) and nuclear factor-kappa B (NF-κB) p65 in the lungs were upregulated. Meanwhile, a parallel increase in the levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in the lungs was observed after the induction of SAP. Treatment with SSBE significantly reduced the expression of p-Akt and p-p65 in the lungs and attenuated the severity of SAP-associated ALI compared to the SAP group at 12 h and 24 h. In summary, this study showed that SSBE has beneficial effects on SAP-associated ALI, probably through the PI3-K/Akt signaling pathways by suppressing the NF-κB activities.


[Expression of human interleukin-1 receptor antagonist in the transfected chondrocytes of temporomandibular joint].
To investigate the expression of the human interleukin-1 receptor antagonist (hIL-1ra) in the transfected chondrocytes of temporomandibular joint (TMJ). Chondrocytes of TMJ in vitro were transfected by hIL-1ra gene via cationic liposome as a medium. The stable transfected cells were selected by G418. The proliferations of the transduced cell were examined with the growth curve, cell population doubling time. The protein expressing in different periods was detected by immunocytochemistry and enzyme-linked immunosorbent assay (ELISA). The proliferation suppression of gene transfected cells fell significantly with compared to normal cells. The expression of hIL-1ra was detected in the cell plasma and the cell culture supernatant. The highest expression of IL-1ra protein was at the time of 48 hours after gene transfection. The transiently transfected cells were secreted IL-1ra protein continuously 28 days and the stably transduced cells were secreted IL-1ra protein till 72 days. This study showed that hIL-1ra protein expressed positively in the cell plasma and the culture supernatant after gene transfection within a certain periods.


Endodontic and surgical treatment of root damage caused by orthodontic miniscrew placement.
Miniscrews are being increasingly used for anchorage control in orthodontics. Despite the concern over root damage caused by miniscrews, there are few reports of precise clinical evaluations and appropriate management of that damage. In the case presented herein, the root damage caused by the placement of miniscrews was repaired by root canal treatment and surgical intervention. A 44-year-old man received orthodontic treatment for intrusion of the left maxillary first molar with a miniscrew anchorage system. During that treatment, the miniscrews had fallen out and had to be reinserted more than 6 times in the same area. Two years later, the patient complained of a spontaneous pain in the maxillary left molar region. Although the patient received root canal treatment, intraoral sinus tracts could still be detected, and the patient's discomfort persisted. Periradicular surgery revealed that the persistent infection was related to root surface damage caused by orthodontic miniscrew placement. Healing was achieved by a combination of root canal treatment and surgical intervention. Scanning electron microscopy of the damaged distobuccal root apex revealed a mature biofilm consisting of a network of matrix that contained mostly rod-like and spherical bacteria. At a 12-month recall checkup, the patient was free of pain. A repeat periapical radiograph revealed reduction of the pretreatment radiolucent lesion. More careful planning of miniscrew placement is necessary to lessen the danger of root damage. Furthermore, a precise evaluation of both root and pulpal damage and careful consideration of the choice of optimal treatment modality are needed.


Counting nuclei released from microcarrier-based cultures using pro-fluorescent nucleic acid stains and volumetric flow cytometry.
Counting nuclei released from intact cells is a convenient and reliable approach to assess cell density during microcarrier-based culture of adherent cells. However, commonly used methods for counting nuclei, such as crystal violet staining and quantification with a hemocytometer/automated imaging system or a Coulter counter, are imprecise, laborious and, limited in throughput. Here, we describe the use of high-affinity pro-fluorescent nucleic acid stains and volumetric flow cytometry for automated counting of nuclei released from cells attached to microcarriers with improved precision and high sample throughput. This simple procedure facilitates rapid and precise assessment of cell attachment, survival, and proliferation on microcarriers, and can provide information about the cell cycle, all without the need for cell detachment. Consequently, various microcarrier-based applications, from small-scale multi-factor experiments to large-scale functional genetic screens and clinical/industrial cultures, could be enhanced by this approach.


A conceptualisation of scale-up and sustainability of social innovations in global health: a narrative review and integrative framework for action.
The scale-up and sustainability of social innovations for health have received increased interest in global health research in recent years; however, these ambiguous concepts are poorly defined and insufficiently theorised and studied. Researchers, policymakers, and practitioners lack conceptual clarity and integrated frameworks for the scale-up and sustainability of global health innovations. Often, the frameworks developed are conceived in a linear and deterministic or consequentialist vision of the diffusion of innovations. This approach limits the consideration of complexity in scaling up and sustaining innovations. By using a systems theory lens and conducting a narrative review, this manuscript aims to produce an evidence-based integrative conceptual framework for the scale-up and sustainability of global health innovations. We conducted a hermeneutic narrative review to synthetise different definitions of scale-up and sustainability to model an integrative definition of these concepts for global health. We have summarised the literature on the determinants that influence the conditions for innovation success or failure while noting the interconnections between internal and external innovation environments. The internal innovation environment includes innovation characteristics (effectiveness and testability, monitoring and evaluation systems, simplification processes, resource requirements) and organisational characteristics (leadership and governance, organisational change, and organisational viability). The external innovation environment refers to receptive and transformative environments; the values, cultures, norms, and practices of individuals, communities, organisations, and systems; and other contextual characteristics relevant to innovation development. From these syntheses, we proposed an interconnected framework for action to better guide innovation researchers, practitioners, and policymakers in incorporating complexity and systemic interactions between internal and external innovation environments in global health.


In vitro antiviral and antibacterial activity of commercial intravenous immunoglobulin preparations--a potential role for adjuvant intravenous immunoglobulin therapy in infectious diseases.
The identification of specific antimicrobial activity of intravenous immunoglobulin (IVIG) preparations against particular microbial pathogens can assist in determining their therapeutic potential for specific infectious diseases. We analysed five different commercial IVIG preparations for the presence of antibodies directed against a large panel of viral, bacterial, fungal and parasitic pathogens. All IVIG batches contained high activity against herpesviruses types 1, 2, 6 and 7, as well as against varicella zoster virus, Epstein-Barr virus (EBV), measles, mumps, rubella and parvovirus B19. Some IVIG batches also had a significant activity against adenovirus and Saint Louis encephalitis virus. The IVIGs held high activity against several bacterial pathogens, including Mycoplasma pneumonia, Chlamydia pneumonia, Helicobacter pylori and tetanus. No activity was found against various parasitic and fungal pathogens. Our findings may provide further support for the use of IVIG for the prevention and treatment of infections caused by specific viral and bacterial pathogens.


Vitamin status of inpatients with chronic cephalgia and dysfunction pain syndrome and effects of a vitamin supplementation.
66 female inpatients with dysfunction pain syndrome, chronic cephalgia and facial pain participated in a randomized, placebo-controlled double-blind study, half the patients receiving a multivitamin preparation for 12 days and the other half a placebo. The biochemically determined vitamin status at the start of the study revealed gaps in the coverage of the vitamin supply, particularly with regard to the vitamins thiamin, riboflavin and folic acid. 65% of the patients showed a subclinical vitamin deficiency of two or more vitamins. With regard to the development of pain during the study no statistically significant differences could be determined, however, between the active-treatment and placebo groups. Nevertheless, a clear reduction in pain was more frequently observed in the active-treatment group, and a deterioration of pain more frequently in the placebo group. A reduction in pain was reported more often by patients in whom the values of alpha-ETK, alpha-EGOT, folic acid and cyanocobalamin improved in the course of the study. Vitamin administration in physiological doses evidently have only weak effects on the behavior of pain; analgesic vitamin effects may be presumed in the case of correspondingly high therapeutic doses for a prolonged period.


Modulation of Fronto-Striatal Functional Connectivity Using Transcranial Magnetic Stimulation.
Background: The fronto-striatal network is involved in various motor, cognitive, and emotional processes, such as spatial attention, working memory, decision-making, and emotion regulation. Intermittent theta burst transcranial magnetic stimulation (iTBS) has been shown to modulate functional connectivity of brain networks. Long stimulation intervals, as well as high stimulation intensities are typically applied in transcranial magnetic stimulation (TMS) therapy for mood disorders. The role of stimulation intensity on network function and homeostasis has not been explored systematically yet. Objective: In this pilot study, we aimed to modulate fronto-striatal connectivity by applying iTBS at different intensities to the left dorso-lateral prefrontal cortex (DLPFC). We measured individual and group changes by comparing resting state functional magnetic resonance imaging (rsfMRI) both pre-iTBS and post-iTBS. Differential effects of individual sub- vs. supra-resting motor-threshold stimulation intensities were assessed. Methods: Sixteen healthy subjects underwent excitatory iTBS at two intensities [90% and 120% of individual resting motor threshold (rMT)] on separate days. Six-hundred pulses (2 s trains, 8 s pauses, duration of 3 min, 20 s) were applied over the left DLPFC. Directly before and 7 min after stimulation, task-free rsfMRI sessions, lasting 10 min each, were conducted. Individual seed-to-seed functional connectivity changes were calculated for 10 fronto-striatal and amygdala regions of interest with the SPM toolbox DPABI. Results: Sub-threshold-iTBS increased functional connectivity directly between the left DLPFC and the left and right caudate, respectively. Supra-threshold stimulation did not change fronto-striatal functional connectivity but increased functional connectivity between the right amygdala and the right caudate. Conclusion: A short iTBS protocol applied at sub-threshold intensities was not only sufficient, but favorable, in order to increase bilateral fronto-striatal functional connectivity, while minimizing side effects. The absence of an increase in functional connectivity after supra-threshold stimulation was possibly caused by network homeostatic effects.


Regulation of muscle atrophy-related genes by the opposing transcriptional activities of ZEB1/CtBP and FOXO3.
Multiple physiopathological and clinical conditions trigger skeletal muscle atrophy through the induction of a group of proteins (atrogenes) that includes components of the ubiquitin-proteasome and autophagy-lysosomal systems. Atrogenes are induced by FOXO transcription factors, but their regulation is still not fully understood. Here, we showed that the transcription factor ZEB1, best known for promoting tumor progression, inhibits muscle atrophy and atrogene expression by antagonizing FOXO3-mediated induction of atrogenes. Compared to wild-type counterparts, hindlimb immobilization in Zeb1-deficient mice resulted in enhanced muscle atrophy and higher expression of a number of atrogenes, including Atrogin-1/Fbxo32, MuRF1/Trim63, Ctsl, 4ebp1, Gabarapl1, Psma1 and Nrf2. Likewise, in the C2C12 myogenic cell model, ZEB1 knockdown augmented both myotube diameter reduction and atrogene upregulation in response to nutrient deprivation. Mechanistically, ZEB1 directly represses in vitro and in vivo Fbxo32 and Trim63 promoter transcription in a stage-dependent manner and in a reverse pattern with MYOD1. ZEB1 bound to the Fbxo32 promoter in undifferentiated myoblasts and atrophic myotubes, but not in non-atrophic myotubes, where it is displaced by MYOD1. ZEB1 repressed both promoters through CtBP-mediated inhibition of FOXO3 transcriptional activity. These results set ZEB1 as a new target in therapeutic approaches to clinical conditions causing muscle mass loss.


Effect of manual therapy on music students with playing-related musculoskeletal disorders: a prospective study.
Playing Related Musculoskeletal Disorders (PRMD) belong to the most prevalent medical ailments affecting musicians' health and career. This study documents the effect of a physiotherapeutic treatment as well as functional impairments of PRMD on the musculoskeletal system. In total, 32 music students suffering from PRMD were examined in Hanover Medical School (MHH) before and after they received twelve physiotherapeutic treatments, which were carried out over 20 min each over 6 weeks. Additionally, 32 healthy music students, matched by age and gender, were examined at one time point in the MHH to explore which musculoskeletal restrictions are associated with PRMD. The examination included the evaluation of the pain on the Visual Analogue Scale for pain (VAS), a body composition, and body posture measurement, the finger-to-floor distance, the range of motion of the cervical spine, the pressure pain and muscular hypertension examination, the temporomandibular joint-test, the Beighton score screening test, and the testing of the widespread pain score (WSP). After analyzing the data of the patient group (PG) a significant reduction of pain level on the VAS from an average pain of 6.31 to 3.53 was found (large effect). Additionally, a significant reduction of the pressure pain of the M. levator scapulae, the M. rhomboideus, the M. sternocleidomastoideus on the left side and the paravertebral muscles of the cervical spine on the right side after the treatment of the patients could be detected. Regarding the WSP, the positive testing significantly differed, showing a 28% positive testing in the patient group vs. a positive testing of 9% in the control group (CG). As hypermobility is a common phenomenon in musicians, the percentage of those being diagnosed with generalized hypermobility by using the Beighton score in both groups (PG: 37.5%; CG: 25%) was remarkably higher compared to previous studies. In this study, a short course of manual therapy, client tailored for each musician's specific problem, was shown to reduce pain levels in musicians with PRMD.


Tissue levels of WR-1065, the active metabolite of amifostine (Ethyol), are equivalent following intravenous or subcutaneous administration in cynomolgus monkeys.
Amifostine (Ethyol) is a cytoprotective drug approved for the reduction of xerostomia in head and neck cancer when administered to patients receiving postoperative radiation therapy. Although amifostine is approved for intravenous infusion, the off-label subcutaneous route of administration has become more prevalent. Although human patient data indicate higher plasma bioavailability of the active metabolite (WR-1065) following intravenous compared to subcutaneous administration, there are no corresponding data showing human tissue levels of WR-1065 following either route of administration due to the difficulty in obtaining human specimens. In our study we compared plasma and tissue pharmacokinetics of WR-1065 in primates following both routes of administration. Monkeys received amifostine at a dose of 260 mg/m2 either intravenously or subcutaneously. Plasma samples were analyzed for total WR-1065 by reverse-phase high-pressure liquid chromatography (HPLC) and fluorescence detection up to 4 h after amifostine administration. Tissues were analyzed for free WR-1065 by reverse-phase HPLC and electrochemical detection 30 and 60 min after administration. Following intravenous administration, plasma WR-1065 levels peaked rapidly and showed a bi-exponential decline, while following subcutaneous administration WR-1065 levels rose slowly and declined exponentially. The relative plasma bioavailability of WR-1065 given subcutaneously was lower at 30 and 60 min. Interestingly, after 30 min, tissues showed equal or slightly greater concentrations of WR-1065 following subcutaneous administration. Levels following 60 min were comparable following both routes. The plasma bioavailability studies performed in primates confirm human plasma data. Expanding the study to evaluate primate tissue levels of WR-1065 revealed that despite lower plasma bioavailability following subcutaneous administration, tissue levels of the active metabolite were surprisingly greater than or equal to those measured in animals that received the drug intravenously. These studies strengthen the argument for subcutaneous administration of amifostine in radiation oncology.


Receptive field organization determines pyramidal cell stimulus-encoding capability and spatial stimulus selectivity.
Sensory systems must operate over a wide range of spatial scales, and single neuron receptive field (RF) organization may contribute to the ability of a neuron to encode information about stimuli having different spatial characteristics. Here we relate the RF organization of sensory neurons to their ability to encode time-varying stimuli, using linear stimulus estimation, measures of information transfer, and more conventional analysis techniques. The electrosensory systems of weakly electric fish are recognized as very tractable model systems for studies of sensory processing because behaviorally relevant stimuli are generated easily and related to known behaviors and because a detailed anatomical database is available to guide the design and interpretation of experiments. Receptive fields of neurons within the first central electrosensory-processing region have an antagonistic center-surround organization; the RF area varies with cell type, with dendritic morphology, and with the spontaneous activity patterns of the cell. Functional consequences of variations in center-surround organization were assessed by comparing responses to two spatial stimulus patterns that mimic naturalistic stimuli and that provide input to the center alone or to the center plus surround. Measures of the quality of stimulus estimation (coding fraction) and information transmission (mutual information) as well as traditional measures of responsiveness consistently demonstrate that, for cells having large surrounds, the activation of both receptive field components degrades the ability to encode time-varying stimuli. The loss of coding efficiency with center-surround stimulation probably results from cancellation of balanced excitatory and inhibitory inputs. However, cells with small surrounds relative to centers perform well under all spatial stimulus regimes.


Structure-based computational screening of 470 natural quercetin derivatives for identification of SARS-CoV-2 Mpro inhibitor.
Coronavirus disease 2019 (COVID-19) is a global pandemic infecting the respiratory system through a notorious virus known as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to viral mutations and the risk of drug resistance, it is crucial to identify new molecules having potential prophylactic or therapeutic effect against SARS-CoV-2 infection. In the present study, we aimed to identify a potential inhibitor of SARS-CoV-2 through virtual screening of a compound library of 470 quercetin derivatives by targeting the main protease-Mpro (PDB ID: 6LU7). The study was carried out with computational techniques such as molecular docking simulation studies (MDSS), molecular dynamics (MD) simulations, and molecular mechanics generalized Born surface area (MMGBSA) techniques. Among the natural derivatives, compound 382 (PubChem CID 65604) showed the best binding affinity to Mpro (-11.1 kcal/mol). Compound 382 interacted with LYS5, TYR126, GLN127, LYS137, ASP289, PHE291, ARG131, SER139, GLU288, and GLU290 of the Mpro protein. The SARS-CoV-2 Mpro-382 complex showed acceptable stability during the 100 ns MD simulations. The SARS-CoV-2 Mpro-382 complex also showed an MM-GBSA binding free energy value of -54.0 kcal/mol. The binding affinity, stability, and free energy results for 382 and Mpro were better than those of the native ligand and the standard inhibitors ledipasvir and cobicistat. The conclusion of our study was that compound 382 has the potential to inhibit SARS-Cov-2 Mpro. However, further investigations such as in-vitro assays are recommended to confirm its in-silico potency.


[Detection of hepatic lesions in patients with multiple injuries. Value of the determination of blood glutamo-pyruvic transaminase].
Serum glutamic pyruvic transaminase (S.G.P.T.) was measured in a series of 39 patients with multiple injuries in order to test its value in detecting liver lesion. An increase above five times the upper limit of the normal value was found in 15 out of the 20 patients having a liver injury and in all of those in whom S.G.P.T. was measured within the first 24 hours following the trauma. In contrast, a similar elevation was observed only in two out of the 19 patients without liver injury. It is suggested that S.G.P.T. determination should be routinely performed in patients with multiple injuries when abdominal signs are poor or concealed by associated lesions. A marked elevation of S.G.P.T. seems in any case suggestive enough to advise a liver arteriogram if hemodynamic conditions allow to perform it.


Comprehension of direct and indirect sarcastic remarks in children and adolescents with Tourette's syndrome.
Previous research has reported that aspects of social cognition such as nonliteral language comprehension are impaired in adults with Tourette's syndrome (TS), but little is known about social cognition in children and adolescents with TS. The present study aims to evaluate a measure of sarcasm comprehension suitable for use with children and adolescents (Experiment 1), and to examine sarcasm comprehension in children and adolescents with TS-alone or TS and attention deficit hyperactivity disorder (ADHD; Experiment 2). In Experiment 1, the measure of sarcasm comprehension was found to be sensitive to differences in nonliteral language comprehension for typically-developing children aged 10 to 11 years old compared to children aged 8 to 9 years old; the older group performed significantly better on the comprehension of scenarios ending with either direct or indirect sarcastic remarks, whereas the two age groups did not differ on the comprehension of scenarios ending with sincere remarks. In Experiment 2, both the TS-alone and TS+ADHD groups performed below the level of the control participants on the comprehension of indirect sarcasm items but not on the comprehension of direct sarcasm items and sincere items. Those with TS+ADHD also performed below the level of the control participants on measures of interference control and fluency. The findings are discussed with reference to the possible contribution of executive functioning and mentalizing to the patterns of performance.


Small Intestinal Bacterial Overgrowth Affects the Responsiveness to Colchicine in Familial Mediterranean Fever.
Familial Mediterranean fever (FMF) is an autosomal recessive disease due to a MEFV gene mutation. Since Helicobacter pylori infection has been described to increase the severity and frequency of FMF attacks, we evaluate if overgrowth of small intestinal bacterial (SIBO), associated with a release of bacterial products, can affect the response to colchicine in FMF patients poorly responsive to colchicine. We revised our Periodic Fever Centre database to detect FMF patients who were poorly responsive to colchicine, without a well-defined cause of drug resistance. They were evaluated for SIBO presence, then treated with decontamination therapy. Among 223 FMF patients, 49 subjects show colchicine resistance, and no other known causes of colchicine unresponsiveness has been found in 25 patients. All 25 patients underwent glucose breath test; 20 (80%) of them were positive, thus affected by SIBO. After a successful decontamination treatment, 11 patients (55%) did not show FMF attacks during the following three months (p < 0.01), while 9 of them revealed a significant reduction of the number of attacks compared to three months before (p < 0.01). The SIBO eradication improves laboratory and clinical features of FMF patients. Thus, patients with unresponsiveness to colchicine treatment should be investigated for SIBO.


Relative sensitivities among avian species to individual and mixtures of aryl hydrocarbon receptor-active compounds.
Dioxins and dioxin-like compounds (DLCs) are potent toxicants to most vertebrates. Sensitivities to DLCs vary among species. In the present study, the sensitivities of avian species (chicken [Gallus gallus], ring-necked pheasant [Phasianus colchicus], and Japanese quail [Coturnix japonica]) to some polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) were determined by using species-specific, in vitro, transactivation assays based on a luciferase reporter gene under control of species-specific aryl hydrocarbon receptors. In ring-necked pheasant and Japanese quail, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was not the most potent inducer of toxic effects. Especially for Japanese quail, the relative potency values of most of 9 PCDD/Fs tested were greater than for TCDD. The rank order of avian species sensitivities to DLCs was chicken > ring-necked pheasant > Japanese quail. Effects of binary mixtures of TCDD, 2,3,7,8-tetrachlorodibenzofuran, and 2,3,4,7,8-pentachlorodibenzofuran were strictly additive. Moreover, we also found that the primary DLCs that were responsible for most of the potency of the DLC mixtures can be deduced by using ordination in a multidimensional space defined by the avian species sensitivities. Overall, the relative potency and the species sensitivities of these chemicals could guide risk assessments to wild species when exposure to mixtures of DLCs in the environment.


Plastic-crystalline solid-state electrolytes: Ionic conductivity and orientational dynamics in nitrile mixtures.
Many plastic crystals, molecular solids with long-range, center-of-mass crystalline order but dynamic disorder of the molecular orientations, are known to exhibit exceptionally high ionic conductivity. This makes them promising candidates for applications as solid-state electrolytes, e.g., in batteries. Interestingly, it was found that the mixing of two different plastic-crystalline materials can considerably enhance the ionic dc conductivity, an important benchmark quantity for electrochemical applications. An example is the admixture of different nitriles to succinonitrile, the latter being one of the most prominent plastic-crystalline ionic conductors. However, until now, only few such mixtures were studied. In the present work, we investigate succinonitrile mixed with malononitrile, adiponitrile, and pimelonitrile to which 1 mol. % of Li ions was added. Using differential scanning calorimetry and dielectric spectroscopy, we examine the phase behavior and the dipolar and ionic dynamics of these systems. We especially address the mixing-induced enhancement of the ionic conductivity and the coupling of the translational ionic mobility to the molecular reorientational dynamics, probably arising via a "revolving-door" mechanism.


Adult neurogenesis in the hippocampus from a perspective of discrimination and generalization: a hypothesis.
The function of adult neurogenesis in the dentate gyrus is not yet completely understood, though many competing theories have attempted to explain the function of these newly-generated neurons. Most theories give adult neurogenesis a role in aiding known hippocampal/dentate gyrus functions. Other theories offer a novel role for these new cells based on their unique physiological qualities, such as their low excitability threshold. Many behavioral tests have been used to test these theories, but results have been inconsistent and often contradictory. Substantial variability in tests and protocols may be at least partially responsible for the mixed results. On the other hand, conflicting results arising from the same tests can serve as aids in elucidating the function of adult neurogenesis. Here, we offer a hypothesis that considers the cognitive nature of tasks commonly used to assess the function of adult neurogenesis, and introduce a dichotomy between tasks focused on discrimination vs. generalization. We view these two aspects as opposite ends of the continuous spectrum onto which traditional tests can be mapped. We propose that high neurogenesis favors behavioral discrimination while low adult neurogenesis favors behavioral generalization of a knowledge or rule. Since many tasks require both, the effects of neurogenesis could be cancelled out in many cases. Although speculative, we hope that our view presents an interesting and testable hypothesis of the effect of adult neurogenesis in traditional behavioral tasks. We conclude that new, carefully designed behavioral tests may be necessary to reach a final consensus on the role of adult neurogenesis in behavior.


Dynamic control of diffraction angle and separation properties of wavelength and polarization by quaternary liquid crystal grating.
A quaternary liquid crystal (LC) grating simultaneously performs dynamic control of diffraction angle, polarization, and wavelength-separation properties as shown in the following: (1) Diffraction orders in which light waves are diffracted can be selected by applying a voltage, (2) the efficiency of each diffraction order can be controlled depending on a wavelength of an incident beam, and (3) a pair of counter-rotated circular polarizations or linear polarizations with an orthogonal relationship are diffracted simultaneously, and this property can be controlled by applying a voltage. These diffraction properties and LC alignment structures are proposed based on theoretical analyses using Jones calculus, and their properties are now demonstrated experimentally. The quaternary LC grating can be used as an advanced optical element for industrial applications such as tunable polarization beam splitters and dynamic switching of propagation directions of light depending on wavelength.


Clinical Factors Associated with Long Fluoroscopy Time in Percutaneous Coronary Interventions to the Culprit Lesion of Non-ST-Segment Elevation Myocardial Infarction.
The clinical outcomes of patients with non-ST-segment elevation myocardial infarction (NSTEMI) were comparable or even worse than those with ST-segment elevation myocardial infarction (STEMI). Although successful percutaneous coronary intervention (PCI) to the culprit lesions of NSTEMI would improve the clinical outcomes, some PCI require long fluoroscopy time, reflecting the difficulty of PCI. This study aims to find clinical factors associated with long fluoroscopy time in PCI to the culprit lesion of NSTEMI. We included 374 patients and divided those into the conventional fluoroscopy time (n = 302) and long fluoroscopy time (n = 72) groups according to the quintiles of fluoroscopy time. Clinical and angiographic parameters were compared between the two groups. Calcification and tortuosity were significantly more severe in the long fluoroscopy time group than in the conventional fluoroscopy time group. The prevalence of previous coronary artery bypass grafting (CABG) and bifurcation lesions was significantly greater in the long fluoroscopy time group than in the conventional fluoroscopy time group. In the multivariate stepwise logistic regression analysis, previous CABG (odds ratio [OR], 3.368; 95% confidence interval [CI], 1.407-8.064; P = 0.006), bifurcation lesion (OR, 2.407; 95% CI, 1.285-4.506; P = 0.006), excessive tortuosity (versus mild to moderate tortuosity; OR, 4.095; 95% CI, 1.159-14.476; P = 0.029), and moderate to severe calcification (versus none to mild; OR, 5.792; 95% CI, 3.254-10.310; P < 0.001) were significantly associated with long fluoroscopy time. In conclusion, previous CABG, bifurcation, excessive tortuosity, and moderate to severe calcification were associated with long fluoroscopy time. Our study provided a reference for PCI operators to identify the difficulties in PCI to the culprit lesion of NSTEMI.


Parapatric distribution and sexual competition between two tick species, Amblyomma variegatum and A. hebraeum (Acari, Ixodidae), in Mozambique.
Amblyomma variegatum and A. hebraeum are two ticks of veterinary and human health importance in south-east Africa. In Zimbabwe they occupy parapatric (marginally overlapping and juxtaposed) distributions. Understanding the mechanisms behind this parapatry is essential for predicting the spatio-temporal dynamics of Amblyomma spp. and the impacts of associated diseases. It has been hypothesized that exclusive competition between these species results from competition at the levels of male signal reception (attraction-aggregation-attachment pheromones) or sexual competition for mates. This hypothesis predicts that the parapatry described in Zimbabwe could also be present in other countries in the region. To explore this competitive exclusion hypothesis we conducted field surveys at the two species' range limits in Mozambique to identify areas of sympatry (overlapping areas) and to study potential interactions (communicative and reproductive interference effects) in those areas. At sympatric sites, hetero-specific mating pairs were collected and inter-specific attractiveness/repellent effects acting at long and short distances were assessed by analyzing species co-occurrences on co-infested herds and co-infested hosts. Co-occurrences of both species at sampling sites were infrequent and localized in areas where both tick and host densities were low. At sympatric sites, high percentages of individuals of both species shared attachment sites on hosts and inter-specific mating rates were high. Although cross-mating rates were not significantly different for A. variegatum and A. hebraeum females, attraction towards hetero-specific males was greater for A. hebraeum females than for A. variegatum females and we observed small asymmetrical repellent effects between males at attachment sites. Our observations suggest near-symmetrical reproductive interference between A. variegatum and A. hebraeum, despite between-species differences in the strength of reproductive isolation barriers acting at the aggregation, fixation and partner contact levels. Theoretical models predict that sexual competition coupled with hybrid inviability, greatly reduces the probability of one species becoming established in an otherwise suitable location when the other species is already established. This mechanism can explain why the parapatric boundary in Mozambique has formed within an area of low tick densities and relatively infrequent host-mediated dispersal events.