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Increases in the scale and complexity of behavioral data pose an increasing challenge for data analysis. A common strategy involves replacing entire behaviors with small numbers of handpicked, domain-specific features, but this approach suffers from several crucial limitations. For example, handpicked features may miss important dimensions of variability, and correlations among them complicate statistical testing. Here, by contrast, we apply the variational autoencoder (VAE), an unsupervised learning method, to learn features directly from data and quantify the vocal behavior of two model species: the laboratory mouse and the zebra finch. The VAE converges on a parsimonious representation that outperforms handpicked features on a variety of common analysis tasks, enables the measurement of moment-by-moment vocal variability on the timescale of tens of milliseconds in the zebra finch, provides strong evidence that mouse ultrasonic vocalizations do not cluster as is commonly believed, and captures the similarity of tutor and pupil birdsong with qualitatively higher fidelity than previous approaches. In all, we demonstrate the utility of modern unsupervised learning approaches to the quantification of complex and high-dimensional vocal behavior. | Mice, Inbred DBA |
Facial nerve schwannoma is a very rare benign tumor representing less than 1% of intrapetrous lesions. Our patient is a forty-one year old female who has suffered from recurrent right facial palsy for the last six years. She was first misdiagnosed as having Bell's palsy and received corticosteroids which resulted in little improvement. She then had facial nerve decompression surgery which resulted in a partial improvement. Since then, she has suffered from recurrent attacks of facial palsy. Two years ago, she came to our hospital seeking further treatment options. The final diagnosis made by MRI was a possible facial nerve tumor. To obtain a better facial outcome, total tumor removal was performed through the middle cranial fossa approach along with facial-hypoglossal nerve end-to-side anastomosis through transmastoid approach. Her hearing was preserved, and she obtained a better facial outcome than that of her preoperative level. In conclusion, facial nerve schwannoma has the potential to be misdiagnosed as Bell's palsy which might lead to a delay in diagnosis, and end-to-side neurorrhaphy may be an effective alternative in a selected case. | Geniculate Ganglion |
A Gram-stain-negative, aerobic, flagellated, non-spore-forming, rod-shaped bacterium, named B2R-29(T), was isolated from water collected from a crater lake on Da Hinggan mountain, PR China. Strain B2R-29(T) was oxidase- and catalase-positive. On the basis of the results of 16S rRNA gene sequence analyses, strain B2R-29(T) clearly belonged to the family Oxalobacteraceae, class Betaproteobacteria and showed the highest similarity to Undibacterium oligocarboniphilum EM1(T) (97.4 %) and to the other species of Undibacterium (less than 96.8 %). In the phylogenetic tree, strain B2R-29(T) formed a clade with U. oligocarboniphilum EM1(T) and Undibacterium squillarum CMJ-9(T), indicating that is a member of the genus Undibacterium. Digital DNA-DNA hybridization and average nucleotide identity analyses were performed and the values between strain B2R-29(T) and its closely related Undibacterium species were less than 75.1 % and 16.9 %, respectively. The chemotaxonomic data of B2R-29(T) were as follows: major uniquinone, Q-8; predominant polar lipids, phosphatidylethanolamine, diphosphatidylglycerol and phosphatidylglycerol; major fatty acids, C(16 : 0) and summed feature 3 (C(16 : 1) omega7c / C(16 : 1) omega6c); predominant polyamines, putrescine, 2-hydroxyputrescine and spermidine. The DNA G+C content was 51.7 mol% from the genomic sequencing data. In accordance with the phenotypic, physiological and chemotaxonomic properties mentioned above, strain B2R-29(T) represents a novel species of the genus Undibacterium for which the name Undibacterium crateris sp. nov. is proposed. The type strain is B2R-29(T) (=CGMCC 1.13792(T)=KCTC 72018(T)). | Oxalobacteraceae |
Strains of the marine ciliate protist Euplotes crassus produce exclusive terpenoids called euplotins that play an ecological role. Among these derivatives, euplotin C is the main of four secondary metabolites isolated from cultures of this protozoon and represents the sesquiterpene taxonomic marker from E. crassus. Because different terpenoid metabolites of plant origin showed a certain antimicrobial activity, we assessed the compound euplotin C, purified by high-pressure liquid chromatography and solubilized in two solubility enhancers, against the protozoa Leishmania major and Leishmani infantum, the fungus Candida albicans, and nine strains of gram-positive and gram-negative microorganisms. An activity of euplotin C against Leishmania promastigotes was demonstrated (50% lethal doses were 4.6 or 8.1 microg/ml depending on the agent used to solubilize the compound), while the effect was less evident on Candida and nearly absent on bacteria. A nonsignificant cytotoxicity (50% lethal dose, >200 microg/ml) against the J774 cell line was observed. A leishmanicidal activity was also shown by the living, euplotin-producing cells of E. crassus cultured together with promastigotes; this activity increased with time from 10 min to 6 h of incubation. This study provides an initial rationale for the evaluation of euplotin C and other similar natural products as alternative or possibly synergistic compounds for current antiprotozoon chemotherapeutics. | Polymenophorea |
BACKGROUND: The N-terminal pyroglutamyl (pGlu) residue of peptide hormones, such as thyrotropin-releasing hormone (TRH) and luteinizing hormone releasing hormone (LH-RH), confers resistance to proteolysis by conventional aminopeptidases. Specialized pyroglutamyl peptidases (PGPs) are able to cleave an N-terminal pyroglutamyl residue and thus control hormonal signals. Until now, no direct or homology-based three-dimensional structure was available for any PGP. RESULTS: The crystal structure of pyroglutamyl peptidase I (PGP-I) from Bacillus amyloliquefaciens has been determined to 1.6 A resolution. The crystallographic asymmetric unit of PGP-I is a tetramer of four identical monomers related by noncrystallographic 222 symmetry. The protein folds into an alpha/beta globular domain with a hydrophobic core consisting of a twisted beta sheet surrounded by five alpha helices. The structure allows the function of most of the conserved residues in the PGP-I family to be identified. The catalytic triad comprises Cys144, His168 and Glu81. CONCLUSIONS: The catalytic site does not have a conventional oxyanion hole, although Cys144, the sidechain of Arg91 and the dipole of an alpha helix could all stabilize a negative charge. The catalytic site has an S1 pocket lined with conserved hydrophobic residues to accommodate the pyroglutamyl residue. Aside from the S1 pocket, there is no clearly defined mainchain substrate-binding region, consistent with the lack of substrate specificity. Although the overall structure of PGP-I resembles some other alpha/beta twisted open-sheet structures, such as purine nucleoside phosphorylase and cutinase, there are important differences in the location and organization of the active-site residues. Thus, PGP-I belongs to a new family of cysteine proteases. | Pyroglutamyl-Peptidase I |
BACKGROUND: Understanding the university students' perception of Water Pipe smoking addictions and factors behind the rise in the prevalence of Water Pipe smoking will contribute effectively in the prevention strategies and policies development. AIMS: Thus, this study aims to assess the prevalence of Water Pipe smoking among university students and their perceptions on its addiction in Palestine, Jordan, and Turkey, as an initial step to reduce the spread of Water Pipe smoking. METHODS: An online self-structured questionnaire was administered to 2030 selected university students from Palestine, Jordan, and Turkey. Prevalence, knowledge and other related factors concerning Water Pipe smoking and its addiction were compared between university students from three Middle East countries (Palestine, Jordan, and Turkey) using SPSS software for statistical analysis. RESULTS: The overall prevalence of Water Pipe smoking was 31.8%, less than a quarter of university students (21.7%) had ever smoked Water Pipe. The highest percentage of current Water Pipe smokers were Palestinians (36.11%), and the lowest percentage was from Turkey (20.23%). Approximately 43% of Water Pipe smokers believe that they will be addicted to Water Pipe smoking and almost half of them smoke Water Pipe daily. The highest percentage of smokers were university students 25 years old and above. However, the highest percentage of smokers was low monthly income students. The university students living with their families were smoking Water Pipe less frequently than students living in private residencies. CONCLUSIONS: The prevalence of Water Pipe smoking among university students in Palestine and Jordan was high compared to Turkey. It was believed that the Turkish rules and regulations of Water Pipe smoking limit the Water Pipe smoking in Turkey.<br />. | Water Pipe Smoking |
The Supplemental Security Income (SSI) program, established by the Social Security Amendments of 1972 (Public Law 92-603), was designed to provide cash assistance to needy aged, blind, and disabled citizens, and noncitizens lawfully admitted for permanent residence or permanently residing under color of law. Since then, this means-tested program has undergone many legislative changes that affect the eligibility status of noncitizens. This article, presented in three parts, discusses the legislative history of noncitizen eligibility, and details relevant laws enacted since the program's inception; provides current data on the trends and changes of the noncitizen population; and describes the larger population of foreign-born SSI recipients, of which the noncitizens are a part. Data on the number of SSI recipients born abroad but who had become citizens before applying for SSI payments were not previously available. Analytical data are from the Supplemental Security Record (SSR) matched to the Social Security Number Identification (Numident) file. | Emigration and Immigration |
Human brucellosis can be caused by different Brucella spp. When conducting operations in a country with high rates of brucellosis, extra precautions should be taken. Appropriate personal protective measures should be used in situations when close contact with animal carcasses cannot be avoided. Clinical diagnosis, treatment, and prevention are discussed. | Brucellosis |
Positive psychology interventions are an effective means for cultivating flourishing, addressing low levels of wellbeing, and preventing languishing. Peer-led interventions can be a particularly advantageous delivery method of positive psychology interventions, as participants tend to respond more favourably to people that they can identify with personally. Such interventions have been applied in a variety of settings and populations, but the literature on peer-led positive psychology interventions has not yet been summarised. This paper provides a narrative overview of peer-led positive psychology interventions. We reviewed relevant peer-led interventions, assessed the available evidence on their effectiveness, and highlighted promising opportunities for peer-led positive psychology interventions. We found that the majority of the studies were observational in design but showed a high level of acceptability for participants across the reviewed domains. In particular, schools, workplaces, the aged care sector, and community settings are noted as promising target domains for these interventions. However, more studies-particularly high-quality research-will be needed to comprehensively test the effectiveness of peer-led positive psychology interventions. We discuss opportunities for future research in this field. | Psychology, Positive |
A series of novel O-aminoalkyl substituted 7-hydroxycoumarins were synthesized and evaluated for antibacterial and anticancer toxicity. Two different synthetic procedures, conventional and microwave assisted were used, and the structures of the compounds were confirmed by IR, 1H, 13C NMR and MAS spectroscopic data. The molecular and crystal structures of 8-acetyl-7-[2-(1-morpholino)ethoxy]4-methylchromen-2-one in solid state were analyzed by single crystal X-ray diffraction. The compound crystallizes in the monoclinic space group P2(1)/c. The main driving forces for the supramolecular structure are the C-Hcdots, three dots, centeredO hydrogen bonds and the picdots, three dots, centeredpi intermolecular interactions. The most active compounds are those, where the O-aminoalkyl substituent has N,N-diethylamino part, and acetyl group is at C6 or at C8 atoms. | Umbelliferones |
Laboratory rodents are commonly euthanized by exposure to gradually increasing concentrations of carbon dioxide (CO2). Current recommended flow rates range between 10 and 30% chamber vol/min and result in insensibility before exposure to painful concentrations (<40%). However, this method causes dyspnea, indicated by deep, rapid breathing. In humans dyspnea is associated with a negative affective experience. Sensations of dyspnea may explain why rodents find CO2 concentrations >3% aversive. This study aimed to assess the effect of CO2 flow rates on time between the onset of dyspnea and various measures of insensibility (recumbency, loss of the righting reflex and loss of the pedal withdrawal reflex) to identify flow rates that minimize the potential experience of dyspnea. The results of this study indicate that a flow rate of 50% chamber vol/min, while holding the CO2 cage concentration just below 40%, minimizes the interval between the onset of labored breathing and recumbency. Using a 50% flow rate this interval averaged (+/- SE) 30.3 +/- 2.9 s versus 49.7 +/- 2.9 s at 20% chamber vol/min (F3,22 = 7.83, P = 0.0013). Similarly, the interval between the onset of labored breathing and loss of the righting reflex averaged 38.2 +/- 2.4 s at a flow rate of 50% versus 59.2 +/- 2.4 s at 20% chamber vol/min of CO2 (F3,22 = 13.62, P < 0.0001). We conclude that higher flow rates reduce the duration of dyspnea, but even at the highest flow rate mice experience more than 30 s between the onset of dyspnea and the most conservative estimate of insensibility. | Euthanasia, Animal |
The beta-blocking potency of three doses of acebutolol (100, 200, and 600 mg three times a day) has been compared to that of propranolol (30, 60, and 180 mg three times a day) in a double-blind crossover study in 10 healthy volunteers (seven men, three women). On the basis of reduction in resting and exercise heart rates, propranolol was three to four times more potent than acebutolol on a milligram-for-milligram basis. Plasma levels showed large interindividual variation for both agents. Plasma levels were weakly correlated with the degree of beta blockade for both acebutolol (r = 0.333, p less than 0.001) and propranolol (r = 0.381, p less than 0.01). Dose and percent beta blockade were more strongly correlated (propranolol, r = 0.503, p less than 0.001; acebutolol, r = 0.574, p less than 0.001). In 11 patients (10 men, one woman) with coronary artery disease, acebutolol at 1 mg/kg infused over 15 minutes decreased heart rate and slowed conduction, increased the refractoriness of the atrioventricular node without a significant change in the atrial refractoriness, and at plasma levels greater than or equal to 1000 ng/ml slowed His-Purkinje conduction. The comparative potency data suggest that the magnitude of the decrease in the resting and exercise-induced changes in heart rate and double product, in relation to dose of acebutolol, provides quantitative indices for judging adequacy by beta blockade in clinical therapeutics. The use of plasma drug levels, however, does not appear to be helpful in judging the adequacy of beta blockade.(ABSTRACT TRUNCATED AT 250 WORDS) | Phenoxypropanolamines |
Dissemination of ovarian cancer is a major clinical challenge and is poorly understood at the molecular level due to a lack of suitable experimental models. During normal development of the Drosophila ovary, a dynamic process called border cell migration occurs that resembles the migratory behavior of human ovarian cancer cells. In this study, we found that myosin VI, a motor protein that regulates border cell migration, is abundantly expressed in high-grade ovarian carcinomas but not in normal ovary and ovarian cancers that behave indolently. Inhibiting myosin VI expression in high-grade ovarian carcinoma cells impeded cell spreading and migration in vitro. Optical imaging and histopathologic studies revealed that inhibiting myosin VI expression reduces tumor dissemination in nude mice. Therefore, using genetic analysis of border cell migration in Drosophila is a powerful approach to identify novel molecules that promote ovarian cancer dissemination and represent potential therapeutic targets. | Myosin Type IV |
Potassium (K) is an essential macronutrient for plant growth and reproduction. HAK5, an Arabidopsis high-affinity K transporter gene, plays an important role in K uptake. Its expression is up-regulated in response to K deprivation and is rapidly down-regulated when sufficient K levels have been re-established. To identify transcription factors regulating HAK5, an Arabidopsis TF FOX (Transcription Factor Full-length cDNA Over-eXpressor) library containing approximately 800 transcription factors was used to transform lines previously transformed with a luciferase reporter gene whose expression was driven by the HAK5 promoter. When grown under sufficient K levels, 87 lines with high luciferase activity were identified, and endogenous HAK5 expression was confirmed in 27 lines. Four lines overexpressing DDF2 (Dwarf and Delayed Flowering 2), JLO (Jagged Lateral Organs), TFII_A (Transcription initiation Factor II_A gamma chain) and bHLH121 (basic Helix-Loop-Helix 121) were chosen for further characterization by luciferase activity, endogenous HAK5 level and root growth in K-deficient conditions. Further analysis showed that the expression of these transcription factors increased in response to low K and salt stress. In comparison with controls, root growth under low K conditions was better in each of these four TF FOX lines. Activation of HAK5 expression by these four transcription factors required at least 310 bp of upstream sequence of the HAK5 promoter. These results indicate that at least these four transcription factors can bind to the HAK5 promoter in response to K limitation and activate HAK5 expression, thus allowing plants to adapt to nutrient stress." | Potassium-Hydrogen Antiporters |
Anaplasma phagocytophilum is the etiologic agent of human granulocytic anaplasmosis (formerly human granulocytic ehrlichiosis), an emerging and potentially deadly disease in the United States, Europe, and Asia. A. phagocytophilum is an obligate intracellular bacterium that displays a unique tropism for neutrophils. Studying this fascinating organism not only provides insight into microbial invasion and intracellular survival strategies, but also offers a unique approach to understanding neutrophil biology and host defense mechanisms. This unit describes the inoculation and maintenance of A. phagocytophilum from an infected blood sample into eukaryotic cell culture or laboratory mice. Cytological staining and immunofluorescent methods for assessing A. phagocytophilum infection are also presented. In addition, this unit describes isolation of viable, host cell-free bacterial preparations from infected cells, as well as the cryopreservation of infected cultures. Lastly, fluorescent labeling of live A. phagocytophilum for the purpose of tracking infection is provided. | Anaplasma phagocytophilum |
We believe the broad clinical, embryological, and radiological spectrum of pulmonary sequestration has not been adequately emphasized. In order to gain clearer understanding of these foregut abnormalities, all cases from the files of three Army Medical Centers were reviewed. Thirty-two patients, the largest single series in the literature, met the criteria for a diagnosis of bronchopulmonary sequestration. Clinical manifestations varied from no symptoms to recurrent pulmonary infection, hemoptysis, and intrapleural hemorrhage. The presence of symptoms strongly correlated (23/32) with air-containing cystic sequestrations. The embryological and radiological spectra as well as appropriate operative therapy are reviewed." | Bronchopulmonary Sequestration |
The aim of this study was to evaluate the efficacy, safety and preference of pre-school children with regard to two different devices for treatment of bronchial asthma with terbutaline. Turbuhaler, a powder inhaler preloaded with pure terbutaline for inhalation, was compared with a pressurized metered dose inhaler, attached to a Nebuhaler. The study had an open, cross-over randomized design. Each treatment period consisted of 2 weeks. Diary cards were filled in every morning and evening by the parents regarding PEF, asthma symptoms, extra inhalations of terbutaline, and side effects. Twenty-one children (mean age 3.9 years) were included in the study. A highly significant (P less than 0.001) increase in peak expiratory flow (PEF) was obtained after inhalation with both devices. The PEF values in the mornings after inhalation of terbutaline with Turbuhaler were significantly higher (P = 0.046) than those with Nebuhaler. Further, the PEF baseline values in the evenings before inhalation were also significantly higher (P = 0.03) with Turbuhaler. No difference was found in asthma symptoms and extra medication between the two devices. Side effects were mild and few with both devices. The parents found Turbuhaler easier to handle and 19 of 21 preferred this device for future use. | Terbutaline |
Mealworms, the larvae of a coleopteran insect Tenebrio molitor L., are capable of eating, living on, and degrading non-hydrolyzable vinyl plastics as sole diet. However, vinyl plastics are carbon-rich but nitrogen-deficient. It remains puzzling how plastic-eating mealworms overcome the nutritional obstacle of nitrogen limitation. Here, we provide the evidence for nitrogen fixation activity within plastic-eating mealworms. Acetylene reduction assays illustrate that the nitrogen-fixing activity ranges from 12.3 +/- 0.7 to 32.9 +/- 9.3 nmol ethylene.h(-1).gut(-1) and the corresponding fixed nitrogen equivalents of protein are estimated as 8.6 to 23.0 microg per day per mealworm. Nature nitrogen isotopic analyses of plastic-eating mealworms provide further evidence for the assimilation of fixed nitrogen as a new nitrogen source. Eliminating the gut microbial microbiota with antibiotics impairs the mealworm's ability to fix nitrogen from the atmosphere, indicating the contribution of gut microbiota to nitrogen fixation. By using the traditional culture-dependent technique, PCR and RT-PCR of nifH gene, nitrogen-fixing bacteria diversity within the gut was detected, and the genus Klebsiella was demonstrated to be an important nitrogen-fixing symbiont. These findings first build the relationship between plastic degradation (carbon metabolism) and nitrogen fixation (nitrogen metabolism) within mealworms. Combined with previously reported plastic-degrading capability and nitrogen-fixing activity, mealworms may be potential candidates for up-recycling of plastic waste to produce protein sources. | Tenebrio |
The receptors for GH and erythropoietin are members of the cytokine receptor superfamily. They are single membrane-spanning proteins that bind ligand in the extracellular domain and couple to cytosolic JAK tyrosine kinases to initiate signaling. The ligand-engaged GH receptor (GHR) and erythropoietin receptor (EpoR) extracellular domains are believed to exist in a dimerized configuration in which a single ligand molecule engages two receptor extracellular domains. The last several years have witnessed a rapid expansion in our knowledge of the structural and functional details of this dimerization process and have forced a reexamination of how the ligand-containing complexes achieve their conformation. For EpoR, there is good evidence that the unliganded receptor is already a preformed dimer that is activated by a ligand-induced change in the receptor conformation. Owing in some measure to the unavailability of the analogous crystal structure of the unliganded GHR extracellular domain, it is still unknown whether GHR adopts a similar preformed dimer/conformational change in response to GH as is found for EpoR. This review critically examines the state of our knowledge pertaining to GHR and EpoR dimerization, noting differences and similarities between the two. | Receptors, Somatotropin |
An exciting development in the sociology of medical education has been its recent return as a distinct scholarly conversation in medical sociology. During the 1980s and 1990s, the sociology of medical education, an historically prominent subfield in sociology, seemed to disappear from the scholarly conversation despite ongoing development in this area. In this narrative review I describe this missing period" of sociology of medical education, discussing complementary explanations for why it receded and describing what research activity did take place during those decades. In reviewing this work, I argue that articulating theoretical advances made within sociology of medical education research during these decades allows us to link foundational research from the 1950s and 1960s with the renaissance of this subfield in the early 2000s. Fundamentally, understanding the intellectual history and development of this subfield supports a broader movement to understand the import of studies of medical training for exploring questions of interest in general sociology." | Sociology, Medical |
The role of the neurosurgeon is critical for initiating preoperative evaluation and care for pineal region tumors. Preoperative evaluation of pineal region tumor can be simplified into a checklist: (1) evaluation for emergent surgical intervention due to symptomatic obstructive hydrocephalus or mass effect; (2) development of a focused differential after acquisition of craniospinal MRI, serum and cerebrospinal fluid oncoprotein levels, and cerebrospinal fluid cytology; and (3) decision on whether a biopsy, surgical resection, or both are necessary. Subsequent biopsy or surgical resection is the first step of tumor management and leads to coordination of consultation with medical and radiation oncology. | Pinealoma |
BACKGROUND: Autoimmune disease is a refractory disease. Accumulating Evidence has revealed that the manipulation of mesenchymal stem cells may have the potential to control or even treat autoimmune diseases. Human gingiva-derived mesenchymal stem cells (GMSCs) are emerging as a new line of mesenchymal stem cells that have displayed some potential advantages in controlling and treating autoimmune diseases. OBJECTIVE: In this review, we briefly update the current understanding on the biology of GMSCs and their effects on preventing and treating autoimmune diseases. CONCLUSION: The availability of gingival mesenchymal stem cells (GMSCs), together with their potent capacity of multi-directional differentiation and inflammatory modulation, making GMSCs an ideal subtype of MSCs in treating autoimmune disease. Our and other studies have launched the earliest appraisal on GMSCs and carried out a lot of biological researches. The clinical trial of GMSCs on patients with autoimmune diseases will further approve their therapeutic effects, as well as its cellular and molecular mechanisms." | Mesenchymal Stem Cell Transplantation |
This study evaluates consumer preference from the perspective of neuroscience when a choice is made among a number of cars, one of which is an electric car. Consumer neuroscience contributes to a systematic understanding of the underlying information processing and cognitions involved in choosing or preferring a product. This study aims to evaluate whether neural measures, which were implicitly extracted from brain activities, can be reliable or consistent with self-reported measures such as preference or liking. In an EEG-based experiment, the participants viewed images of automobiles and their specifications. Emotional and attentional stimuli and the participants' responses, in the form of decisions made, were meticulously distinguished and analyzed via signal processing techniques, statistical tests, and brain mapping tools. Long-range temporal correlations (LRTCs) were also calculated to investigate whether the preference of a product could affect the dynamic of neuronal fluctuations. Statistically significant spatiotemporal dynamical differences were then evaluated between those who select an electric car (which seemingly demands specific memory and long-term attention) and participants who choose other cars. The results showed increased PSD and central-parietal and central-frontal coherences at the alpha frequency band for those who selected the electric car. In addition, the findings showed the emergence of LRTCs or the ability of this group to integrate information over extended periods. Furthermore, the result of clustering subjects into two groups, using statistically significant discriminative EEG measures, was associated with the self-report data. The obtained results highlighted the promising role of intrinsically extracted measures on consumers' buying behavior. | Attention |
Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disease in cats. However, scarce data on its prevalence are available in Brazil. Persian cats and Persian-related breeds were assessed by molecular genotyping for a C to A transversion in exon 29 of PKD1 gene to determine ADPKD prevalence in a Brazilian population. Genomic DNA extracted from peripheral whole blood or oral swabs samples was used to amplify exon 29 of PKD1 gene employing a PCR-RFLP methodology. From a total of 616 animals, 27/537 Persian and 1/17 Himalayan cats showed the single-nucleotide variant (C to A) at position 3284 in exon 29 of feline PKD1. This pathogenic variation has been identified only in heterozygous state. The prevalence of ADPKD in Persian cats and Persian-related breeds was 5.03% and 1.6%, respectively. There was no significant association between feline breed, gender or age with ADPKD prevalence. Of note, the observed ADPKD prevalence in Persian cats and Persian-related breeds in Brazil was lower than the ones reported in other parts of the world. This finding may be related to genetic counseling and consequent selection of ADPKD-free cats for reproduction." | Polycystic Kidney, Autosomal Dominant |
This Position Statement represents the consensus of an expert committee convened by the European Society of Endodontology (ESE) on External Cervical Resorption (ECR). The statement is based on current clinical and scientific evidence as well as the expertise of the committee. The primary aim is to provide a current authoritative position on the aetiology, histopathology, clinical presentation and management of ECR, and also to highlight areas where there is minimal evidence. Previously published review articles provide more detailed background information and the basis for this position statement (International Endodontic Journal 51, 1205, 2018, International Endodontic Journal 51, 1224, 2018). It is intended that this position statement will be updated at appropriate intervals, as further evidence emerges." | Dental Physiological Phenomena |
Movement of the malaria parasite into a host erythrocyte during invasion is thought to involve polymerization of parasite actin. We have used F-actin affinity chromatography to isolate actin-binding proteins from Plasmodium knowlesi merozoites, in an attempt to identify proteins responsible for regulating parasite actin polymerization during invasion. Five major proteins, of molecular masses 75, 70, 48, 40 and 34 kDa, were reproducibly eluted from the F-actin columns. The 70 kDa actin-binding protein was identified by tryptic peptide microsequencing as heat shock protein-70 kDa (HSC70); this identification was confirmed by Western blotting with anti-HSC70 antibody, and binding of the protein to ATP-agarose. A doublet of 32/34-kDa proteins coeluted with parasite HSC70 from the F-actin and ATP-agarose columns; a complex of these three proteins was also observed by gel filtration chromatography Highly enriched fractions containing the Plasmodium HSC70/32/34 complex inhibited the polymerization of rabbit skeletal muscle actin, in vitro. This capping activity was calcium-independent, and abrogated by phosphatidylinositol 4,5-bisphosphate. The average length of the actin filaments polymerized in presence of the HSC70/32/34-kDa complex was significantly shorter than in the absence of the complex, consistent with a capping activity. The capping or uncapping of actin filament ends by the HSC70/32/34-kDa complex during invasion could provide a mechanism for localized actin filament growth and movement of the parasite into the host cell. | Microfilament Proteins |
SARM1 is an inducible NAD(+) hydrolase that is the central executioner of pathological axon loss. Recently, we elucidated the molecular mechanism of SARM1 activation, demonstrating that SARM1 is a metabolic sensor regulated by the levels of NAD(+) and its precursor, nicotinamide mononucleotide (NMN), via their competitive binding to an allosteric site within the SARM1 N-terminal ARM domain. In healthy neurons with abundant NAD(+), binding of NAD(+) blocks access of NMN to this allosteric site. However, with injury or disease the levels of the NAD(+) biosynthetic enzyme NMNAT2 drop, increasing the NMN/ NAD(+) ratio and thereby promoting NMN binding to the SARM1 allosteric site, which in turn induces a conformational change activating the SARM1 NAD(+) hydrolase. Hence, NAD(+) metabolites both regulate the activation of SARM1 and, in turn, are regulated by the SARM1 NAD(+) hydrolase. This dual upstream and downstream role for NAD(+) metabolites in SARM1 function has hindered mechanistic understanding of axoprotective mechanisms that manipulate the NAD(+) metabolome. Here we reevaluate two methods that potently block axon degeneration via modulation of NAD(+) related metabolites, 1) the administration of the NMN biosynthesis inhibitor FK866 in conjunction with the NAD(+) precursor nicotinic acid riboside (NaR) and 2) the neuronal expression of the bacterial enzyme NMN deamidase. We find that these approaches not only lead to a decrease in the levels of the SARM1 activator NMN, but also an increase in the levels of the NAD(+) precursor nicotinic acid mononucleotide (NaMN). We show that NaMN inhibits SARM1 activation, and demonstrate that this NaMN-mediated inhibition is important for the long-term axon protection induced by these treatments. Analysis of the NaMN-ARM domain co-crystal structure shows that NaMN competes with NMN for binding to the SARM1 allosteric site and promotes the open, autoinhibited configuration of SARM1 ARM domain. Together, these results demonstrate that the SARM1 allosteric pocket can bind a diverse set of metabolites including NMN, NAD(+), and NaMN to monitor cellular NAD(+) homeostasis and regulate SARM1 NAD(+) hydrolase activity. The relative promiscuity of the allosteric site may enable the development of potent pharmacological inhibitors of SARM1 activation for the treatment of neurodegenerative disorders. | Allosteric Regulation |
The compound 3-methylcholanthrene (3-MC) is an environmental pollutant belonging to the PAHs, which reportedly have the potential to disrupt the endocrine systems of animals. In the present study, 4-week-old male and female mice were given 3-MC through their diet at a dose of 0.5 mg/kg of chow for 6 weeks before pregnancy. The first filial (F(1)) generation offspring of exposed or unexposed parental mice were sacrificed at the age of 5 or 10 weeks (F(1)-5 W or F(1)-10 W), and the potential effects on the F(0) and F(1) offspring were evaluated. The results showed that the serum and testicular testosterone (T) levels and the genes involved in T synthesis in F(0) males and male F(1)-5 W individuals born from female mice exposed to 3-MC were significantly decreased. In addition, histological analysis suggested that exposure to 3-MC significantly disrupted testicular morphology in F(0) mice and in the offspring of female mice exposed to 3-MC. Further investigation revealed that genes involved in spermatogenesis, such as Phosphoglycerate kinase 2 (Pgk2), Glial cell derived neurotrophic factor (Gdnf), Myeloblastosis oncogene (Myb), DEAD box helicase 4 (Ddx4) and KIT proto-oncogene receptor tyrosine kinase (Kit), were suppressed in these mice. However, the adverse effects of parental 3-MC exposure on the adolescent mice were mitigated when they grew to adulthood, which was verified by studies on F(1)-10 W mice. Our results suggest that female exposure to 3-MC has the potential to disrupt the endocrine system and spermatogenesis in male offspring; nevertheless, the adverse effects might be mitigated with age. | Methylcholanthrene |
In 1997, we identified a novel peptide, catestatin (CST: bovine chromogranin A [CHGA](344-364): RSMRLSFRARGYGFRGPGLQL; human CHGA(352-372): SSMKLSFRARGYGFRGPGPQL), which is a potent inhibitor of nicotinic-cholinergic-stimulated catecholamine secretion. CST shows characteristic inhibitory effects on nicotinic cationic (Na(+), Ca(2+)) signal transduction, which are specific to the neuronal nicotinic receptor. Utilizing systematic polymorphism discovery at the human CHGA locus we discovered three human variants of CST: G(364)S, P(370)L, and R(374)Q that showed differential potencies towards the inhibition of catecholamine secretion. In humans, CHGA is elevated and its processing to CST is diminished in hypertension. Diminished CST is observed not only in hypertensive individuals but also in the early-normotensive offspring of patients with hypertension, suggesting that an early deficiency of CST might play a pathogenic role in the subsequent development of the disease. Consistent with human findings, prevention of endogenous CST expression by targeted ablation (knockout) of the mouse Chga locus (Chga-KO) resulted in severe hypertension that can be rescued" specifically by replacement of the CST peptide. CST acts directly on the heart to inhibit the inotropic and lusitropic properties of the rodent heart and also acts as a potent vasodilator in rats and humans. While the G(364)S CST variant caused profound changes in human autonomic activity and seemed to reduce the risk of developing hypertension, CST replacement rescued Chga-KO mice from dampened baroreflex sensitivity. In addition, CST has been shown to induce chemotaxis and acts as an antimicrobial as well as an antimalarial peptide. The present review summarizes these multiple actions of CST." | Chromogranin A |
I investigated whether soil moisture affects relative fitness of females and hermaphrodites and sex ratio in a gynodioecious plant with nuclear-cytoplasmic sex inheritance. I contrast these results with those from species with strictly nuclear sex inheritance. I performed a manipulative watering experiment on seed fitness of the two sexes, and field studies measuring seed fitness and sex ratio as a function of soil moisture. In the dry site, watered hermaphrodites produced approximately twice as many seeds as unwatered hermaphrodites, with little treatment effect on female seed production. Over a natural soil moisture gradient, the ratio of female to hermaphrodite seed production was higher in dry than in wet sites. These data show that the seed fitness advantage of females is a function of soil moisture. Despite this, regression of soil moisture on the sex ratio of 23 populations was not significant. These results indicate a sex-dependent effect of soil moisture on resource allocation to seeds that does not translate into a strong effect on sex ratio. This is consistent with theory based on genomic conflict in which sex ratios are predicted to be only partly determined by fitness differences of the sexes. | Hydrophyllaceae |
Acipimox, a nicotinic acid derivative in clinical use for the treatment of hyperlipidaemia, incorporates a free carboxylic acid and an N-oxide moiety, functionalities known to interact with the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) and inhibit its activity. Herein we report that acipimox acts as a low micromolar CA inhibitor (CAI) against most human (h) isoforms possessing catalytic activity, hCA I - XIV. By using computational techniques (docking and molecular dynamics simulations), we propose that acipimox coordinates through its carboxylate group to the zinc ion from the enzyme active site cavity, whereas the N-oxide group is hydrogen-bonded to the proton shuttle His residue in some isoforms (hCA I) or to active site Thr or Gln residues in other isoforms (hCA II, III, IV, VII, etc). As some CA isoforms are involved in lipogenesis, these data may be useful for the design of more effective CAIs with antiobesity activity. | Pyrazines |
PURPOSE OF REVIEW: Hematopoietic stem-cell (HSCT) and solid organ transplant (SOT) recipients are particularly at risk to develop herpes zoster and its complications. A recently approved nonlive, adjuvanted recombinant zoster vaccine (aRZV) is a potential candidate to provide durable prevention of herpes zoster. This review summarizes current scientific evidence and expert recommendations for its use in these populations and offers practical clinical guidance. RECENT FINDINGS: Recent clinical trials have shown aRZV to be well tolerated and efficacious in the prevention of herpes zoster, even in the elderly. Data are emerging that this vaccine might also be effective in immunocompromised individuals, such as SOT and HSCT recipients. Evidence is sparse regarding optimal timing of vaccination and durability of responses. However, several specialized societies have already established expert-based aRZV immunization recommendations for these vulnerable populations. SUMMARY: Practical considerations, safety concerns, and timing of vaccine administration vary from one immunocompromised subpopulation to another. Initial studies show that aRZV has a favorable safety and immunogenicity profile in SOT and HSCT recipients. However, data are sparse, particularly in allogeneic HSCT, and practical recommendations are mostly based on expert opinion. Additional research is needed to offer better insight on aRZV administration in immunocompromised patients. | Herpes Zoster Vaccine |
betagamma-crystallins from the eye lens are proteins consisting of two similar domains joined by a short linker. All three-dimensional structures of native proteins solved so far reveal similar pseudo-2-fold pairing of the domains reflecting their presumed ancient origin from a single-domain homodimer. However, studies of engineered single domains of members of the betagamma-crystallin superfamily have not revealed a prototype ancestral solution homodimer. Here we report the 2.35 A X-ray structure of the homodimer of the N-terminal domain of rat betaB2-crystallin (betaB2-N). The two identical domains pair in a symmetrical manner very similar to that observed in native betagamma-crystallins, where N and C-terminal domains (which share approximately 35% sequence identity) are related by a pseudo-2-fold axis. betaB2-N thus resembles the ancestral prototype of the betagamma-crystallin superfamily as it self-associates in solution to form a dimer with an essentially identical domain interface as that between the N and C domains in betagamma-crystallins, but without the benefit of a covalent linker. The structure provides further evidence for the role of two-domain pairing in stabilising the protomer fold. These results support the view that the betagamma-crystallin superfamily has evolved by a series of gene duplication and fusion events from a single-domain ancestor capable of forming homodimers. | Crystallins |
An abnormal upper labial frenum is capable of retracting the gingival margin, creating a diastema, limiting lip movement, and in cases of a high smile line, affecting esthetics also. When an abnormal frenum is present, frenectomy is advised. This technique has been modified in many ways. But in most of the techniques the zone of attached gingiva and esthetics are not considered. This case report highlights a new technique of frenectomy that results in good esthetics, excellent color match, gain in attached gingiva, and healing by primary intention at the site of the thick, extensive abnormal frenum. | Labial Frenum |
The ability to control the movement of nanoparticles remotely and with high precision would have far-reaching implications in many areas of nanotechnology. We have designed a unique dynamic magnetic field (DMF) generator that can induce rotational movements of superparamagnetic iron oxide nanoparticles (SPIONs). We examined whether the rotational nanoparticle movement could be used for remote induction of cell death by injuring lysosomal membrane structures. We further hypothesized that the shear forces created by the generation of oscillatory torques (incomplete rotation) of SPIONs bound to lysosomal membranes would cause membrane permeabilization, lead to extravasation of lysosomal contents into the cytoplasm, and induce apoptosis. To this end, we covalently conjugated SPIONs with antibodies targeting the lysosomal protein marker LAMP1 (LAMP1-SPION). Remote activation of slow rotation of LAMP1-SPIONs significantly improved the efficacy of cellular internalization of the nanoparticles. LAMP1-SPIONs then preferentially accumulated along the membrane in lysosomes in both rat insulinoma tumor cells and human pancreatic beta cells due to binding of LAMP1-SPIONs to endogenous LAMP1. Further activation of torques by the LAMP1-SPIONs bound to lysosomes resulted in rapid decrease in size and number of lysosomes, attributable to tearing of the lysosomal membrane by the shear force of the rotationally activated LAMP1-SPIONs. This remote activation resulted in an increased expression of early and late apoptotic markers and impaired cell growth. Our findings suggest that DMF treatment of lysosome-targeted nanoparticles offers a noninvasive tool to induce apoptosis remotely and could serve as an important platform technology for a wide range of biomedical applications." | Lysosomal-Associated Membrane Protein 1 |
Silicone breast implants are popularly used for breast reconstruction. As more patients receive long-term silicone breast implants, the number of replacement operations will also increase, and some patients prefer to change from silicone breast implantation to tertiary autologous reconstruction. We evaluated the safety of tertiary reconstruction and assessed patient views regarding the two reconstruction methods. We retrospectively analyzed patient backgrounds, surgical characteristics, and silicone breast implantation retention periods until tertiary reconstruction. We designed an original questionnaire to assess patient opinion regarding silicone breast implantation and tertiary reconstruction. Twenty-three patients (24 breasts) with decisive factors of patient-initiated elective surgery (n = 16), contralateral breast cancer occurrence (n = 5), or late-onset infection (n = 2) underwent tertiary reconstruction. The median time from silicone breast implantation to tertiary reconstruction was significantly shorter in patients with metachronous cancer (47 months) than that in those undergoing elective surgery (92 months). Complications included partial flap loss (n = 1), seroma (n = 6), hematoma (n = 5), and infection (n = 1). Total necrosis did not occur. Twenty-one patients responded to the questionnaire. The satisfaction score was significantly higher for abdominal flaps than for silicone breast implants. When presented with the option to select the initial reconstruction method again, 13 of 21 respondents chose silicone breast implantation. Tertiary reconstruction is beneficial because it reduces clinical symptoms and cosmetic complaints and is recommended as a bilateral reconstruction method, especially for patients with metachronous breast cancer. However, silicone breast implants, which are minimally invasive and associated with shorter hospital stays, were simultaneously found to be sufficiently attractive to patients. | Mammaplasty |
The addition of nitrate to cultures of Spirillum itersonii incubated under low aeration produced a diauxic growth pattern in which the second exponential phase was preceded by the appearance of nitrite in the medium. The organism also grew anaerobically in the presence of nitrate. Nitrate reductase activity could be demonstrated in cell-free extracts by use of reduced methyl viologen as the electron donor. The enzyme was located in the supernatant fraction after centrifugation of extracts for 2 hr at 40,000 x g, and it sedimented as a single peak when centrifuged in a sucrose gradient. Nitrate reductase activity was found in cells grown with low aeration without nitrate, but was increased about twofold by addition of nitrate. Enzyme activity was negligible in cells grown with high aeration. The proportion of soluble cytochrome c was increased two- to threefold in cells grown with nitrate. The specific activities of nitrate reductase and soluble cytochrome c rose when nitrate or nitrite was added to cell suspensions incubated with low aeration; nitrite was more effective than nitrate during the early stages of incubation. A nitrate reductase-negative mutant synthesized increased amounts of soluble cytochrome c in response to nitrate or to nitrite in the cell suspension system. It is concluded that enhanced synthesis of soluble cytochrome c does not require the presence of a functional nitrate reductase. | Spirillum |
INTRODUCTION: Training for obstetrics and gynecology residents in second-trimester dilation and evacuation (D&E) procedures is extremely limited despite the Accreditation Council for Graduate Medical Education mandating all residents to receive abortion training. Simulation-based training improves surgical competence, but no second-trimester uterine models exist. The purposes of this study were to create a realistic, low-cost model and to assess the prototype. METHODS: A uterine model was created with 6 silicone cervixes of varying texture and dilations that are interchangeable. The uterus is neoprene and opens to allow for objects to be placed within it for extraction. At a national meeting, experienced D&E surgeons assessed the prototype by using the model and then completing a questionnaire. RESULTS: Twenty-one expert surgeons completed the questionnaires. Participants rated the prototype as useful" or "very useful" for teaching extraction skills and for training in general. Subjects agreed this represented a clinical scenario they were likely to encounter and the model allowed for practicing the necessary steps for performing D&Es. The model cost approximately $35 to fabricate. CONCLUSIONS: Expert surgeons believe that this model accurately and realistically replicates a second-trimester uterus and cervix. This prototype may be used in simulation environments to train obstetrics and gynecology residents." | Dilatation and Curettage |
Patella fractures comprise 1% of all fractures. Treatment options vary based on fracture displacement, classification, and patient factors. Traditionally, nonoperative treatment has been reserved for nondisplaced fractures. Many operative treatments are available with differing indications and levels of success. Tension band constructs have been the most commonly employed approach to fixation, with cerclage wiring for comminuted fractures. Recently, plate fixation of patella fractures has become more popular. Plating constructs offer a low-profile design with stable fixation, allowing for earlier mobilization and potentially improved functional outcomes. Data regarding the long-term outcomes of plating techniques are limited, and further studies are needed. [Orthopedics. 2018; 41(6):e747-e755.]. | Patella |
The reproducibility of electrocardiographic (ECG) recordings in syncopal recurrences and the diagnostic role of nonsyncopal arrhythmias are not well known. The objective of this study was to analyse the reproducibility of the ECG findings recorded with implantable loop recorders in 41 patients with suspected neurally-mediated syncope who were included in the International Study on Syncope of Uncertain Origin-2 study and that had > or =2 events recorded by implantable loop recorders. In these patients, the electrocardiogram obtained with the first documented syncope (index syncope) was compared with other recorded events. Twenty-two patients had > or =2 syncopes, and their electrocardiograms were reproducible in 21 (95%): 15 with sinus rhythm, 5 with asystole, and 1 with ventricular tachycardia; 1 had asystole at first syncope and sinus rhythm at recurrent syncope. In 32 patients with nonsyncopal episodes, an arrhythmia was documented in 9, and all of them had the same arrhythmia during the index syncope (100% reproducibility); conversely, when sinus rhythm was documented (23 patients) during nonsyncopal episodes, an arrhythmia was still documented in 6 during the index syncope (70% reproducibility; p = 0.0004). In conclusion, the ECG findings during the first syncope are highly reproducible in subsequent syncopes. The presence of an arrhythmia during nonsyncopal episodes is also highly predictive of the mechanism of syncope, but the presence of sinus rhythm does not rule out the possibility of arrhythmia during syncope. Therefore the finding of an arrhythmia during a nonsyncopal episode allows the etiologic diagnosis of syncope, and eventually to anticipate treatment, without waiting for syncope. | Syncope, Vasovagal |
BACKGROUND: The primary aim was to estimate the incidence of primary and secondary childhood glaucoma in Scotland over a 2-year period. The secondary aim was to gauge the confidence and experience of ophthalmologists in Scotland in managing these patients. METHODS: A 7 question electronic survey was distributed to all consultant members of the Scottish Paediatric Club and Scottish Glaucoma Club. Respondents were asked to report the number of cases and types of childhood glaucoma they had managed in the last 2 years. Respondents were also asked about experience and confidence in a range of glaucoma procedures, number of patients requiring referral to specialist centres and interest in the development of a centre of excellence in Scotland. RESULTS: The survey returned a 56% response rate, reporting 85 new cases of paediatric glaucoma in Scotland over the preceding 2 years. 11 (12.9%) had primary glaucoma and 74 (87.1%) had secondary glaucoma. The most common subtype of secondary glaucoma was uveitic glaucoma (n = 29). None of the respondents declared confidence or experience in trabeculotomy or goniotomy procedures. Eleven children required referral to a specialist unit outside Scotland. 85.7% of respondents felt Scotland would benefit from a specialist unit for paediatric glaucoma. CONCLUSIONS: This survey reflects an appetite for a specialist service for paediatric glaucoma in Scotland. However, further consideration is needed to determine if there is sufficient patient load to maintain such a service. | Hydrophthalmos |
Ejaculation is a complex and still poorly understood neurological mechanism, at both spinal and cerebral levels as it is closely associated with orgasm. Physiologically, ejaculation is defined as the expulsion of seminal fluid from the urethral meatus and consists of two phases, namely emission and expulsion. Ejaculation is mediated by a spinal control center, referred to as a spinal pattern generator that coordinates sympathetic, parasympathetic and motor (somatic) outflows, integrating the latter with the inputs from the supraspinal sites in brainstem, hypothalamus and preoptic area. Premature ejaculation (PE) is the most common sexual dysfunction among young men, and it has been considered mostly psychogenic in origin, although it can be associated to diverse urological and neurological diseases. On the contrary, retrograde ejaculation and anejaculation are predominantly related to organic causes, particularly to neurogenic ones. Since ejaculation is mostly a spinal reflex, it is comprehensible that ejaculatory disorders are more frequent in spinal cord injury than in other neurological disorders. Over the past decades, research has focused on PE, and evidence from clinical studies showed a beneficial effect of antidepressants for the treatment of men with PE. Other ejaculatory disorders, especially painful ejaculation, have been less investigated and the proper therapy is still controversial. Aim of this review is to provide a comprehensive description of both currently available treatments and most promising future therapies, including assigned patents, for the neurogenic ejaculatory disorders. | Benzylamines |
Molecular imaging is expanding radiologists' territory and holds the promise of personalizing treatment. But a turf war is looming over who has the diagnostic role-radiologists, oncologists or others. We're talking about a whole new way of thinking in terms of diagnosing and treating diseases," David Rollo says." | Nuclear Medicine |
In September 2016, an invasive group A streptococcal disease outbreak occurred among residents of a residential aged care facility. An expert advisory group recommended mass prophylaxis for residents and staff in addition to strict infection control practices to prevent further spread. Whole genome sequencing confirmed the cases were related. | Streptococcus pyogenes |
Chronic lymphocytic leukemia is a neoplasm characterized by the accumulation of monoclonal lymphocytes in blood, bone marrow, and other tissues. Staging of the disease is based on lymphoid mass and the presence of anemia or thrombocytopenia, with prognosis also related to the pattern of bone-marrow involvement, chromosomal abnormalities, and surface membrane phenotype. Transformation to a diffuse large-cell lymphoma or to prolymphocytic leukemia may occur as a terminal event. A number of biochemical and surface membrane abnormalities that may suggest approaches for future clinical investigations have been described. | Leukemia, Lymphoid |
INTRODUCTION: Currently, there is a lack of specific analytical tools for general aviation accidents (GAAs). This has led to loopholes in the prevention of GAAs. METHODS: A Swiss Cheese model for general aviation (SCM-GA) is proposed to identify the human and organizational factors involved in GAAs. In the proposed SCM-GA, 5 categories, 45 subcategories, a general aviation safety management system (GA-SMS) and safety culture were developed based on the classic accident causation models combined with the laws and regulations and safety management practices in the general aviation industry. RESULTS: One GAA was analyzed using SCM-GA. The human and organizational causes revealed by SCM-GA were more complete than the causes revealed through the accident report. The identification results of the deficiencies in the subcategories of GA-SMS and the safety culture were more consistent with the requirements in the general aviation laws and regulations than the organizational factors in the accident report. Based on the subcategories of SCM-GA, 41 GAAs that occurred between 1996 and 2010 in China were statistically analyzed and chi(2) test analyses were performed to estimate the statistical strength of the association between two adjacent subcategories of SCM-GA. The results showed that two adjacent subcategories of SCM-GA were significantly associated. They helped to determine the hidden problems in the accident report based on the path of accident. CONCLUSIONS: SCM-GA is an accident analysis tool that can comprehensively analyze the human and organizational deficiencies involved in GAAs. The accident causes revealed by SCM-GA were more consistent with the general aviation safety management practices. PRACTICAL APPLICATIONS: General aviation companies should establish their own GA-SMS and safety culture based on the subcategories developed herein. Using SCM-GA for routine safety inspection and accident investigation will help the management and the staff make effective safety decisions to effectively prevent GAAs. | Accidents, Aviation |
A distinction is drawn between incomplete grief and grief arising from maturational events such as life-cycle milestones. Treating maturational grief as though it were incomplete grief or using expressions of maturational grief as a sign of important childhood roots for a patient's current problems is likely to be unproductive. | Paternal Deprivation |
A simple method for the study of sugar-nucleotide-dependent multienzyme cascades is highlighted where the use of selectively (13)C-labeled sugar nucleotides and inverse (13)C detection NMR offers fast, direct detection and quantification of reactants and products and circumvents the need for chromatographic separation. The utility of the method has been demonstrated by characterizing four previously uncharacterized sugar nucleotide biosynthetic enzymes involved in calicheamicin biosynthesis. | Carbohydrates |
Monofunctional histidinol phosphate phosphatase from Thermus thermophilus HB8, which catalyzes the dephosphorylation of l-histidinol phosphate, belongs to the PHP family, together with the PHP domain of bacterial DNA polymerase III and family X DNA polymerase. We have determined the structures of the complex with a sulfate ion, the complex with a phosphate ion, and the unliganded form at 1.6, 2.1, and 1.8 A resolution, respectively. The enzyme exists as a tetramer, and the subunit consists of a distorted (betaalpha)7 barrel with one linker and one C-terminal tail. Three metal sites located on the C-terminal side of the barrel are occupied by Fe1, Fe2, and Zn ions, respectively, forming a trinuclear metal center liganded by seven histidines, one aspartate, one glutamate, and one hydroxide with two Fe ions bridged by the hydroxide. In the complexes, the sulfate or phosphate ion is coordinated to three metal ions, resulting in octahedral, trigonal bipyramidal, and tetrahedral geometries around the Fe1, Fe2, and Zn ions, respectively. The ligand residues are derived from the four motifs that characterize the PHP family and from two motifs conserved in histidinol phosphate phosphatases. The (betaalpha)7 barrel and the metal cluster are closely related in nature and architecture to the (betaalpha)8 barrel and the mononuclear or dinuclear metal center in the amidohydrolase superfamily, respectively. The coordination behavior of the phosphate ion toward the metal center supports the mechanism in which the bridging hydroxide makes a direct attack on the substrate phosphate tridentately bound to the two Fe ions and Zn ion to hydrolyze the phosphoester bond. | Histidinol-Phosphatase |
From the end of the 1970s, the promotion of the community and the participation of populations in the health system reinforced the idea that mutual health insurance was a potentially major player in the extension of coverage against health risks. But the history of mutuality in Africa was quickly strewn with pitfalls. The structural adjustment plans and the increase in the financial contribution of users under the impetus of the Bamako initiative put a stop to the spirit of community mutual insurances. Today, mutual insurances are once again at the heart of international and national initiatives with the promotion of the (UHC) Universal Health Coverage. But they must overcome their historical shortcomings through professionalization and compulsory membership. This movement seems to be underway, while at the same time facing the challenge of preserving the place of communities in health systems, a founding principle of the mutualist movement. | Financing, Organized |
Tumor necrosis factor receptor-associated factor 4 (TRAF4) is overexpressed in a variety of carcinomas of different origins, but its role in tumorigenesis remains incompletely understood. Previous studies suggest that TRAF4 promotes epidermal growth factor receptor (EGFR) activation in non-small cell lung cancer (NSCLC). However, the downstream signaling pathway of TRAF4-mediated EGFR activation, as well as its effects on tumor cells, have not been fully elucidated. Here we report that TRAF4 overexpression is associated with increased activity of extracellular signal-regulated kinase 5 (ERK5) in NSCLC tissues. Activation of ERK5 was dependent on TRAF4-mediated EGFR activation, since inhibition of either TRAF4 or EGFR dramatically abolished phosphorylation of ERK5. Mechanistically, EGFR recruited mitogen-activated protein kinase kinase kinase 3 (MEKK3), an upstream kinase of ERK5, in a TRAF4-dependent manner. Thus, our data suggest that an EGFR-TRAF4-MEKK3-ERK5 axis promotes the proliferation of tumor cells, and this may be a potential target for therapeutic intervention of NSCLC. | MAP Kinase Kinase Kinase 3 |
In this study, we investigated the functional roles of Asp40, Asp57, and C-terminal Asn60 in Naja atra cardiotoxin 3 (CTX3) structure and function by modifying these three carboxyl groups with semicarbazide. The conjugation of the carboxyl groups with semicarbazide produced two conformational isomers whose gross and fine structures were different from those of CTX3. The blocking of the carboxyl groups increased the structural flexibility of CTX3 in response to trifluoroethanol-induced effect. Despite presenting modest to no effect on decreasing the induction of permeability in zwitterionic phospholipid vesicles, the carboxyl group-modified CTX3 showed a marked reduction in its permeabilizing effect on anionic phospholipid vesicles in comparison to that of the native protein. Compared with native CTX3, carboxyl group-modified CTX3 exhibited lower activity in inducing membrane leakage in U937 cells. The CD spectra of lipid-bound toxins and the color transition of polydiacetylene/lipid assay showed that the membrane interaction mode of CTX3 was distinctly changed by the modification in the carboxyl groups. Given that the selective modification of Asp40 does not cause the conformational isomerization of CTX3, our data indicate that the carboxyl groups in Asp57 and Asn60 are essential in maintaining the structural topology of CTX3. Furthermore, modification of carboxyl groups changes the interdependence between the infrastructure and the global conformation of CTX3 in modulating membrane permeabilizing activity. | Reptilian Proteins |
Plant growth and development are plastic and canadapt to environmental changes. In this process different plant hormones coordinate to modulate plant growth and environmental interactions. In this article, we describe the individual brassinosteroid (BR) and abscisic acid (ABA) signaling pathways, emphasize the specific regulatory mechanisms between ABA and BR responses and discuss how both phytohormones coordinate growth, development and stress responses in plants. BR signaling is essential for plant development, while ABA signaling is activated to ensure plants survive stress. The crosstalk between BR and ABA, especially protein phosphorylation, protein stability control and downstream transcription control of key components of both pathways are discussed in terms of modulating plant development and stress adaptation. | Brassinosteroids |
The hypothesis that hormonally active compounds in the environment--endocrine disrupters--are having a significant impact on human and ecological health has captured the public's attention like no other toxicity concern since the publication of Rachel Carson's Silent Spring 1962. In the early 1990s, Theo Colborn and others began to synthesize information about the potential impacts of endocrine-mediated toxicity in the scientific literature (Colborn and Clement, 1992) and the popular press (Colborn et al., 1997). Recognizing the possibility of an emerging health threat, the U.S. Environmental Protection Agency (EPA) convened two international workshops in 1995 (Ankley et al., 1997; Kavlock et al., 1996) that identified research needs relative to future risk assessments for endocrine-disrupting chemicals (EDCs). These workshops identified effects on reproductive, neurological, and immunological function, as well as carcinogenesis as the major endpoints of concern and made a number of recommendations for research. Subsequently, the EPA developed a research strategy to begin addressing the recommendations (EPA, 1998a), and the federal government as a whole, working through the White House's Committee on the Environment and Natural Resources, increased funding levels and coordinated research programs to fill the major data gaps (Reiter et al., 1998). In parallel with these research efforts that were attempting to define the scope and nature of the endocrine disruptor hypothesis, the U.S. Congress added provisions to the Food Quality Protection Act (FQPA) and the Safe Drinking Water Act of 1996 to require the testing of food-use pesticides and drinking water contaminants, respectively, for estrogenicity and other hormonal activity. These bills were enacted into law, giving the EPA the mandate to implement them. The EPA, with the help of an external advisory committee, the Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC), determined that other hormonal activity should include androgens and compounds that affect thyroid function, and expanded the mandate to include all chemicals under EPA's jurisdiction, potentially including the 70,000 chemicals regulated under the Toxic Substances Control Act (Endocrine Disruptor Screening and Testing Advisory Committee [EDSTAC], 1998). EDSTAC recommended an extensive process of prioritization, screening, and testing of chemicals for endocrine-disrupting activity, including a screening battery that involves a combination of at least eight in vitro and in vivo assays spanning a number of taxa (EDSTAC, 1998). What started out as a hypothesis has become one of the biggest testing programs conceived in the history of toxicology and the only one that has ever been based on mechanism of action as its premise. As we pass the 10th anniversary of the emergence of the endocrine disruptor hypothesis, it is useful to look back on the progress that has been made in answering the nine questions posed as data gaps in the EPA's research strategy (EPA, 1998a)--not only to see what we have learned, but also to examine whether the questions are still appropriate for the goal, what gaps remain, and what directions should be emphasized in the future. | Endocrine Glands |
The actin cytoskeleton is a primary determinant of cell shape and motility. Studies on actin regulatory proteins are now coupled with studies of the signal transduction that directs actin cytoskeleton reorganization, and we have gained insights into how external stimuli such as chemoattractants drive changes in actin cytoskeleton. Chemoattractants regulate actin regulatory proteins such as the Arp2/3 complex through WASP family proteins, ADF/cofilin downstream of LIM-kinase, and various other phosphoinositide-dependent or -independent pathways. Through branching of actin filaments, Arp2/3 complex-dependent actin polymerization is suffcient to generate the force necessary for protrusion. | Destrin |
Snake venom contains a number of active molecules that have been shown to possess high anti-tumor activities; disintegrins are an excellent example among these. Their ability to interact and bind with integrins suggests that they could be very valuable molecules for the development of new cancer therapeutic approaches. However, in the absence of a clear Lysine-Threonine-Serine (KTS) Disintegrins Integrin interaction model, the exact compound features behind it are still unknown. In this study, we investigated the structural characteristics of three KTS-disintegrins and the interaction mechanisms with the alpha1beta1 integrin receptor using in silico bioinformatics approaches. Normal mode analysis showed that the flexibility of the KTSR motif and the C-terminal region play a key role and influence the KTS-Disintegrin-integrin interaction. Protein-protein docking also suggested that the interaction involving the KTSR motif is highly dependent on the residue following K21, S23 and R24. These findings contribute to a better understanding of the KTS-Disintegrin-Integrin structural differences and their interactions with alpha1beta1 receptors, which could improve the selection process of the best active molecules for antitumor therapies. | Disintegrins |
Limb-girdle muscular dystrophies (LGMDs) represent a major group of muscle disorders. Treatment is sorely needed and currently expanding based on safety and efficacy adopting principles of single-dosing gene therapy for monogenic autosomal recessive disorders. Gene therapy has made in-roads for LGMD and this review describes progress that has been achieved for these conditions. This review first provides a background on the definition and classification of LGMDs. The major effort focuses on progress in LGMD gene therapy, from experimental studies to clinical trials. The disorders discussed include the LGMDs where the most work has been done including calpainopathies (LGMD2A/R1), dysferlinopathies (LGMD2B/R2) and sarcoglycanopathies (LGMD2C/R5, LGMD2D/R3, LGMD2E/R4). Early success in clinical trials provides a template to move the field forward and potentially apply emerging technology like CRISPR/Cas9 that may enhance the scope and efficacy of gene therapy applied to patient care. | Sarcoglycanopathies |
Today it is important for hospital organizations to understand the implications of insurance dealings. After September 11, 2001 the insurance industry had an impact on hospitals and health care organizations. This article looks at Aon Insurance and how they handled this situation. | Organizational Case Studies |
Cry3Aa is a protein that forms crystals naturally in the bacterium Bacillus thuringiensis. Here we report that coexpression of Cry3Aa and a Proteus mirabilis lipase without recombinant fusion results in the efficient passive entrapment of the lipase within the nanoporous channels of the resulting crystals. This Cry3Aa crystal-mediated entrapment provides multiple benefits to the lipase including a high enzyme loading, significantly improved thermostability, increased proteolytic resistance, and the ability to be utilized as a recyclable biodiesel catalyst. These characteristics, along with its greatly simplified method of isolation, highlight the potential of Cry3Aa crystal-mediated enzyme entrapment for use in biocatalysis and other biotechnological applications. | Endotoxins |
To investigate the effects of Centella asiatica (L.) on growth performance, nutrient digestibility and blood composition in piglets, 32 nursery pigs were fed 0.0, 0.5, 1.0 and 2.0% dietary C. asiatica (L.) from 15 to 90 kg BW. At 30 kg BW, nutrient digestibility was measured and at 35 kg BW piglets were vaccinated with Mycoplasma hyopneumoniae. Hematological parameters were checked at 40 and 80 kg BW. Compared with the control, growth performance was not affected. The ether extract, ash and calcium digestibility were lower at 0.5%, and dry matter, crude protein, crude fat, phosphorus and energy digestibility were lower at 1.0% (P<0.05). On hematological values, at 40 kg hematocrit, total white blood cells, neutrophils, eosinophils, basophils, monocytes and lymphocytes were higher at the 2.0% level (P<0.05). Most of these values except basophils and monocytes continued until at 80 kg, at which total white blood cells, neutrophils, eosinophils and lymphocytes were higher even at 1.0% (P<0.05); neutrophil-to-lymphocyte ratio tended to be higher at 2.0% (P<0.03). Cholesterol, triglycerides and antibody levels against M. hyopneumoniae did not differ except that at 40 kg the cholesterol of 0.5% was lower (P<0.05) and M. hyopneumoniae-specific antibodies tended to be higher with increasing levels of C. asiatica (L.) (P<0.07). The result that C. asiatica (L.) could not improve growth performance but increased values of serum hematocrit and white blood cells, and mycoplasma immunity to M. hyopneumoniae might suggest that C. asiatica (L.) has no function to elevate body weight but has the potential to enhance innate immunity. | Centella |
Molecular human identification has conventionally focused on DNA sampling from dense, weight-bearing cortical bone tissue, typically from femora or tibiae. A comparison of skeletal elements from three contemporary individuals demonstrated that elements with high quantities of cancellous bone yielded nuclear DNA at the highest rates, suggesting that preferentially sampling cortical bone may be suboptimal (Mundorff & Davoren, 2014). Despite these findings, the reason for the differential DNA yields between cortical and cancellous bone tissues remains unknown. The primary goal of this work is to ascertain whether differences in bone microstructure can be used to explain differential nuclear DNA yield among bone tissue types observed by Mundorff and Davoren (2014), with a focus on osteocytes and the three-dimensional (3D) quantification of their associated lacunae. Osteocytes and other bone cells are recognized to house DNA in bone tissue, thus examining the density of their lacunae may explain why nuclear DNA yield rates differ among bone tissue types. Lacunae were visualized and quantified using synchrotron radiation-based micro-Computed Tomographic imaging (SR micro-CT). Volumes of interest (VOIs) from cortical and cancellous bone tissues (n=129) were comparatively analyzed from the three skeletons sampled for Mundorff and Davoren's (2014) study. Analyses tested the primary hypothesis that the abundance and density of osteocytes (inferred from their lacunar spaces) vary between cortical and cancellous bone tissue types. Results demonstrated that osteocyte lacunar abundance and density vary between cortical and cancellous bone tissue types, with cortical bone VOIs containing a higher lacunar abundance and density. We found that the osteocyte lacunar density values are independent of nuclear DNA yield, suggesting an alternative explanation for the higher nuclear DNA yields from bones with greater quantities of cancellous bone tissue. The use of SR micro-CT allowed for a scale of analysis that revealed a high range of variation in lacunar abundance in both tissue types. Moreover, high-resolution SR micro-CT imaging revealed potential soft tissue remnants within marrow spaces not visible macroscopically. It is hypothesized that soft tissue remnants observed among the trabeculae of skeletal elements with high quantities of cancellous bone tissue are responsible for the high nuclear DNA yields. These findings have significant implications for bone-sample selection for nuclear DNA analysis in a forensic context when skeletal remains are recovered from the ground surface. | Connective Tissue |
Koala Retrovirus (KoRV) has been associated with neoplasia in the vulnerable koala (Phascolarctos cinereus). However, there are conflicting findings regarding its association with secondary disease. We undertook a large-scale assessment of how the different KoRV subtypes and viral load are associated with Chlamydia pecorum infection and a range of disease pathologies in 151 wild koalas admitted for care to Currumbin Wildlife Hospital, Australia. Viral load (KoRV pol copies per ml of plasma) was the best predictor of more disease pathologies than any other KoRV variable. The predicted probability of a koala having disease symptoms increased from 25% to over 85% across the observed range of KoRV load, while the predicted probability of C. pecorum infection increased from 40% to over 80%. We found a negative correlation between the proportion of env deep sequencing reads that were endogenous KoRV-A and total KoRV load. This is consistent with suppression of endogenous KoRV-A, while the exogenous KoRV subtypes obtain high infection levels. Additionally, we reveal evidence that the exogenous subtypes are directly associated with secondary disease, with the proportion of reads that were the endogenous KoRV-A sequence a negative predictor of overall disease probability after the effect of KoRV load was accounted for. Further, koalas that were positive for KoRV-D or KoRV-D/F were more likely to have urogenital C. pecorum infection or low body condition score, respectively, irrespective of KoRV load. By contrast, our findings do not support previous findings that KoRV-B in particular is associated with Chlamydial disease. Based on these findings we suggest that koala research and conservation programs should target understanding what drives individual differences in KoRV load and limiting exogenous subtype diversity within populations, rather than seeking to eliminate any particular subtype. | Phascolarctidae |
The thyroid hormone receptor and the highly related viral oncoprotein v-erbA are found exclusively in the nucleus as stable constituents of chromatin. Unlike most transcriptional regulators, the thyroid hormone receptor binds with comparable affinity to naked and nucleosomal DNA. In vitro reconstitution experiments and in vivo genomic footprinting have delineated the chromatin structural features that facilitate association with the receptor. Chromatin bound thyroid hormone receptor and v-erbA generate Dnase I hypersensitive sites independent of ligand. The unliganded thyroid hormone receptor and v-erbA associate with a corepressor complex containing NCoR, SIN3, and histone deacetylase. The enzymatic activity of the deacetylase and a chromatin environment are essential for the dominant repression of transcription by both the unliganded thyroid hormone receptor and v-erbA. In the presence of ligand, the thyroid hormone receptor undergoes a conformational change that weakens interactions with the corepressor complex while facilitating the recruitment of transcriptional coactivators such as p300 and PCAF possessing histone acetyltransferase activity. The ligand-bound thyroid hormone receptor directs chromatin disruption events in addition to histone acetylation. Thus, the thyroid hormone receptor and v-erbA make very effective use of their stable association with chromatin and their capacity to alter the chromatin environment as a major component of the transcription regulation process. This system provides an exceptionally useful paradigm for investigating the structural and functional consequences of targeted chromatin modification. | Oncogene Proteins v-erbA |
Snails were kept in self-cleaning housing chambers in an artificially controlled environment. Mating was frequent under long days (18 h light) and rare under short days (8 h light) regardless of whether the snails were kept at 15 degrees C or 20 degrees C. An interaction between photoperiod and temperature was observed for egg laying. The number of eggs laid (45-50/snail) and the frequency of egg laying (90-130%) were greater in long than in short days (16-35/snail and 27-77%) but a temperature of 20 degrees C redressed, to some extent, the inhibitory effect of short days. At both temperatures only long photoperiods brought about cyclic reproduction over a period of 16 weeks, confirming the synchronizing role of photoperiod on the neuroendocrine control of egg laying in this species of snail. | Copulation |
Regulation of the Bone Morphogenetic Protein (BMP) signaling pathway is essential for the normal development of vertebrate gastrointestinal (GI) tract, but also for the differentiation of the digestive mesenchymal layer into smooth muscles and submucosal layer. Different studies demonstrated that Bapx1 (for bagpipe homeobox homolog 1) negatively regulates the BMP pathway, but its precise expression pattern during the development and the differentiation of the GI tract mesenchyme actually remains to be examined. Here, we present the spatio-temporal expression profile of Bapx1 in the chick GI tract. We show that Bapx1 is first expressed in the undifferentiated mesenchyme of the gizzard and the colon. After the differentiation of the digestive mesenchyme, we found Bapx1 strongly expressed in the gizzard smooth muscle and in the submucosa layer of the colon. This expression pattern provides new insights into the roles of Bapx1 during the regionalization of the GI tract and the differentiation of the digestive mesenchyme of the colon and the stomach. | Gizzard, Avian |
Peroxisome proliferator-activated receptors, PPARalpha, PPARbeta/delta, and PPARgamma, are a group of nuclear receptors that function as transcriptional regulators of lipid metabolism, energy homeostasis, and inflammation. Given the role of metabolism imbalance under pathological states of the heart, PPARs have emerged as important therapeutic targets, and accumulating evidence highlights their protective role in the improvement of cardiac function under diverse pathological settings. Although the role of PPARs in the regulation of cardiac substrate utilization preference and energy homeostasis is well documented, their effects related to the regulation of cellular inflammatory and redox responses in the heart are less studied. In this review, we provide an overview on recent progress with respect to understanding the role of the nonmetabolic effects of PPARs in cardiac dysfunction, namely during ischemia/reperfusion injury, hypertrophy, and cardiac failure, and highlight the mechanisms underlying the protective effects against inflammation, oxidative stress, and cell death. The role of receptor-independent, nongenomic effects of PPAR agonists is also discussed." | Peroxisome Proliferator-Activated Receptors |
In recent times, there has been a growing interest in exploring microbial strains that exhibit enhanced erythritol productivity. Nonetheless, the lack of advanced synthetic biology tools has limited rapid strain development. In this study, the CRISPR/Cas9 system was employed to genetically modify Yarrowia lipolytica at the chromosomal level, which could improve the production of erythritol while saving the time required to markers recovery, and realizing the rapid construction of high-erythritol strains. Firstly, the basic strain E004 was generated by increasing the efficiency of homologous recombination and regulating the erythritol degradation pathway. Secondly, eleven key gene targets and a strong promoter 8UAS1B(XPR2)-P(TEFin) was obtained by target screening and promoter engineering. Finally, based on modular pathway engineering and morphological engineering, the high production of erythritol was achieved successfully. The best-engineered strain E326 produced 256 g/L erythritol in a 5-L bioreactor, which is the highest production level reported so far in Y. lipolytica. | Yarrowia |
The synthesis of an 8-deazafolate analogue of the intermediate in the methylation of 2'-deoxyuridylate is described. Alkylation of diethyl 5,6,7,8-tetrahydro-8-deazafolate with 3'-O-acetyl-5-(bromomethyl)-2'-deoxyuridine 5'-[bis-(trichlorethyl) phosphate], followed by removal of the trichloroethyl groups with a Zn/Cu couple and mild saponification, gave the target inhibitor N-[4-[[[2-amino-3,4,5,6,7, 8-hexahydro-4-oxo-5-[(2'-deoxyuridin-5-yl)methyl]-pyrido[3,2-d] pyrimidin-6-yl]methyl]amino]benzoyl]-L-glutamic acid 5'-monophosphate. The free nucleoside and the 5'-(methyl phosphate) diester were similarly prepared. Each of these reactions yielded a pair of diastereoisomers about C-6 of the reduced deazafolate in approximately a 1:1 ratio. These diastereoisomeric mixtures were evaluated as inhibitors of thymidylate synthetase derived from human tumor (HeLa) cells. The 5'-monophosphate was a potent inhibitor, competitive with respect to both 2'-deoxyuridylate (Ki = 0.06 microM) and tetrahydrofolate (Ki = 0.25 microM). In contrast, the nucleoside and the nucleotide methyl ester were poorer inhibitors by more than 3 orders of magnitude, attesting to the importance of the anionic function at the nucleoside 5'-position in the affinity of an inhibitor for the enzyme active site. | Uracil Nucleotides |
As the environmental temperature prominently influences diverse biological aspects of the animals, thermosensation and the subsequent information processing in the nervous system has attracted much attention in biology. Thermotaxis in the nematode Caenorhabditis elegans is an ideal behavioral paradigm by which to address the molecular mechanism underlying thermosensory transduction. Molecular genetic analysis in combination with other physiological and behavioral studies revealed that sensation of ambient temperature is mediated mainly by cyclic guanosine monophosphate (cGMP) signaling in thermosensory neurons. The information of the previously perceived temperature is also stored within the thermosensory neurons, and the consequence of the comparison between the past and the present temperature is conveyed to the downstream interneurons to further regulate the motor-circuits that encode the locomotion. | Thermosensing |
Recent investigations have expanded our knowledge of the regulatory bone marrow (BM) niche, which is critical in maintaining and directing hematopoietic stem cell (HSC) self-renewal and differentiation. Osteoblasts, mesenchymal stem cells (MSCs), and CXCL12-abundant reticular (CAR) cells are niche components in close association with HSCs and have been more clearly defined in immune cell function and homeostasis. Importantly, cellular inhabitants of the BM niche signal through G protein-coupled surface receptors (GPCRs) for various appropriate immune functions. In this article, recent literature on BM niche inhabitants (HSCs, osteoblasts, MSCs, CAR cells) and their GPCR mechanistic interactions are reviewed for better understanding of the BM cells involved in immune development, immunologic disease, and current immune reconstitution therapies. | Bone Marrow Cells |
This review focuses on the plasticity of the regulation of a particular neuroendocrine transducer cell, the melanotrope cell in the pituitary pars intermedia of the amphibian Xenopus laevis. This cell type is a suitable model to study the relationship between various external regulatory inputs and the secretion of an adaptive endocrine message, in this case the release of alpha-melanophore-stimulating hormone, which activates skin melanophores to darken when the animal is placed on a dark background. Information about the environmental conditions is processed by various brain centres, in the hypothalamus and elsewhere, that eventually control the activity of the melanotrope cell regarding hormone production and secretion. The review discusses the roles of these hypothalamic and extrahypothalamic nuclei, their neurochemical messengers acting on the melanotrope, and the external stimuli they mediate to control melanotrope cell functioning. | Melanotrophs |
The increasing awareness of the role of obligate anaerobic bacteria in the aetiology of oral disease has led to an interest in their chemotherapeutic control. Many drugs are capable of eliminating anaerobes but in instances where these bacteria are acting as sole or major pathogens it is desirable to remove these specifically. The nitroimidazole group of drugs is specifically anti-anaerobic in nature and includes metronidazole, nimorazole and tinidazole. This paper reviews the literature on metronidazole. This drug is absorbed well from the gastrointestinal tract and can be detected at bactericidal levels in blood and saliva within 1 h of ingestion. The mode of action of metronidazole is unknown but thought to concern intracellular reduction of the molecule. The drug acts specifically against anaerobes and does not disturb the commensal aerobic flora; resistance very rarely develops. The dosage recommended for use in dentistry would appear to be very safe. Metronidazole has important interactions with alcohol, disulfiram and warfarin and there are contraindications to its use. Metronidazole has been proved to be efficacious in treating: acute ulcerative gingivitis, pericoronitis, certain periapical infections, some cases of osteomyelitis and infected socket. The drug may be of use in cases of chronic progressive periodontitis where anaerobes are implicated as pathogens. | Pericoronitis |
Genome-scale metabolic models are widely used to enhance our understanding of metabolic features of organisms, host-pathogen interactions and to identify therapeutics for diseases. Here we present iTMU798, the genome-scale metabolic model of the mouse whipworm Trichuris muris. The model demonstrates the metabolic features of T. muris and allows the prediction of metabolic steps essential for its survival. Specifically, that Thioredoxin Reductase (TrxR) enzyme is essential, a prediction we validate in vitro with the drug auranofin. Furthermore, our observation that the T. muris genome lacks gsr-1 encoding Glutathione Reductase (GR) but has GR activity that can be inhibited by auranofin indicates a mechanism for the reduction of glutathione by the TrxR enzyme in T. muris. In addition, iTMU798 predicts seven essential amino acids that cannot be synthesised by T. muris, a prediction we validate for the amino acid tryptophan. Overall, iTMU798 is as a powerful tool to study not only the T. muris metabolism but also other Trichuris spp. in understanding host parasite interactions and the rationale design of new intervention strategies. | Trichuris |
Human infections with A/Jiangxi-Donghu/346/2013 (H10N8) virus have raised concerns about its pandemic potential. In order to develop a vaccine against this virus, the immunogenicity of its haemagglutinin protein was evaluated in mice. Using both whole-virion and recombinant subunit protein vaccines, we showed that two doses of either vaccine elicited neutralizing antibody responses. The protective efficacy of the vaccine-induced responses was assessed using a reverse-genetics-derived H10 reassortant virus on the A/Puerto Rico/8/34 (H1N1) backbone. The reassortant virus replicated efficiently in the respiratory tract of unvaccinated mice whereas vaccinated mice were completely protected from challenge, with no detectable viral load in the lower respiratory tract. Finally, the serum neutralizing antibody responses elicited by the H10 vaccines also exhibited cross-neutralizing activity against three heterologous wild-type H10 viruses. Collectively, these findings demonstrate that different vaccine platforms presenting the H10 haemagglutinin protein induce protective immunity." | Influenza A Virus, H10N8 Subtype |
This review article summarizes the different fields of research at the Laboratoire d'Electrochimie Physique et Analytique at the Ecole Polytechnique Federale de Lausanne. The research areas covered include charge transfer reactions at soft interfaces, bio-analytical microchips and electrophoretic methods, electrochemical ionization methods for mass spectrometry and Scanning Electrochemical Microscopy (SECM). | Proteomics |
Nursing students' learning of adult and pediatric palliative care is a daunting experience. An effective initial teaching strategy using a Memory Quilt activity can improve nursing students' interpersonal and communication skills and help prepare them for end-of-life caring. These skills help students meet patient and family needs, as they transition to care settings." | Hospice and Palliative Care Nursing |
INTRODUCTION: Improving the quality and activity of clinicians' practice improves patient care. Performance-related human resource management (HRM) is an established approach to improving individual practice but with limited use among clinicians. A framework for performance-related HRM was developed from successful practice in non-healthcare organisations centred on distributive leadership and locally provided, validated and interpreted performance measurement. This study evaluated the response of medical and non-clinical managers to its implementation into a large secondary healthcare organisation. METHODS: A semistructured qualitative questionnaire was developed from themes identified during framework implementation and included attitudes to previous approaches to measuring doctors' performance, and the structure and response to implementation of the performance-related HRM framework. Responses were analysed through a process of data summarising and categorising. RESULTS: A total of 29, from an invited cohort of 31, medical and non-clinical managers from departmental to executive level were interviewed. Three themes were identified: (1) previous systems of managing clinical performance were considered to be ineffective due to insufficient empowerment of medical managers and poor quality of available performance data; (2) the implemented framework was considered to address these needs and was positively received by medical and non-clinical managers; (3) introduction of performance-related HRM required the involvement of the whole organisation to executive level and inclusion within organisational strategy, structure and training. CONCLUSIONS: This study suggests that a performance-related HRM framework may facilitate the management of clinical performance in secondary healthcare, but is dependent on the design and methods of application used. Such approaches contrast with those currently proposed for clinicians in secondary healthcare in the UK and suggest that alternative strategies should be considered. | Secondary Care Centers |
A methodology has been developed for the complete compositional characterization of lithium titanate (LTO) using neutron activation, which is quite challenging and no literature report is available so far. The concept of thermal neutron induced in-situ chain reactions (6)Li(n,alpha)(3)H and (16)O((3)H,n)(18)F has been used for the determination of Li and O through the measurement of (18)F activity. The method is capable of analyzing Li and O in percentage level as reported in the present analysis of two types of lithium titanate samples. Spectroscopic interference of the elements which can directly or indirectly affect the outcome, were evaluated meticulously. Determination of Ti was carried out using fast neutron activation through the product isotopes like (47)Sc, (48)Sc, generated via (n,p) nuclear reactions. Fast neutron activation methodology seems to be advantageous for Ti determination over thermal neutron activation, as it offers self validation through different isotopes and multiple gamma lines. | Neutrons |
The crystal structure of Thermus thermophilus seryl-transfer RNA synthetase, a class 2 aminoacyl-tRNA synthetase, complexed with a single tRNA(Ser) molecule was solved at 2.9 A resolution. The structure revealed how insertion of conserved base G20b from the D loop into the core of the tRNA determines the orientation of the long variable arm, which is a characteristic feature of most serine specific tRNAs. On tRNA binding, the antiparallel coiled-coil domain of one subunit of the synthetase makes contacts with the variable arm and T psi C loop of the tRNA and directs the acceptor stem of the tRNA into the active site of the other subunit. Specificity depends principally on recognition of the shape of tRNA(Ser) through backbone contacts and secondarily on sequence specific interactions. | RNA, Transfer, Amino Acyl |
In accordance with provisions of OMB Circular A-11 section 12.5(a), revised reimbursement rates have been established by the Department of Veterans Affairs for inpatient and outpatient medical care furnished to beneficiaries of other Federal agencies during FY 1995. These rates will be charged for such medical care provided at health care facilities under the direct jurisdiction of the Secretary on and after December 1, 1994. | Hospitals, Veterans |
Trauma care delivery is a complex team-based task that requires deliberate practice. The COVID-19 pandemic has not diminished the importance of excellent trauma team dynamics. However, the pandemic hampers our ability to gather safely and train together. A mitigating solution is the provision of high-fidelity simulation training in a virtual setting. The Simulated Trauma and Resuscitation Team Training (S.T.A.R.T.T.) course has provided multidisciplinary trauma team members with skills in crisis resource management (CRM) for nearly 10 years. It has promoted collaborative learning from coast to coast, as the course typically runs at our national surgical and trauma meetings. In response to COVID-19 challenges, the course content has been modified to virtually connect 2 centres in different provinces simultaneously. High participant satisfaction suggests that the new virtual E-S.T.A.R.T.T course is able to continue to help providers develop important CRM skills in a multidisciplinary setting while remaining compliant with COVID-19 safety precautions. | Traumatology |
BACKGROUND: Selective sinus replacement (SSR) allows a tailored repair approach in patients with sinus of Valsalva or asymmetric aortic root aneurysm. SSR avoids the need for coronary reimplantation for nondiseased sinuses and shortens operative time, although potential for late growth of retained sinuses exists. This study describes selection of patients and assesses operative outcomes and late root dimensions after SSR. METHODS: From 2006 to 2020, 60 patients underwent SSR at a single referral institution. Mixed effect models were used to assess trajectory of postoperative growth of remaining sinuses, adjusting for age of the patient, valve morphology, and baseline root diameter. RESULTS: Median age of the patients was 57 (interquartile range [IQR], 48-65) years. Twenty-four (40%) had a bicuspid aortic valve. Most patients (n = 55 [92%]) underwent single sinus replacement (n = 46 noncoronary, n = 9 right), whereas 5 (8%) underwent repair of both the right and noncoronary sinuses. Concomitant aortic valve replacement was performed in 15 patients (25%); aortic valve repair with internal ring annuloplasty or cusp plication was performed in 37 (62%). There was no operative death, stroke, renal failure, or respiratory failure. Median preoperative root diameter was 53 mm (IQR, 51-56 mm) vs 42 mm (IQR, 39-45 mm) at median imaging follow-up of 34 (IQR, 13-49) months. Rate of midterm root growth was 0.2 mm/y, and there were no late root reinterventions. CONCLUSIONS: For patients with sinus of Valsalva or asymmetric root aneurysm, SSR is associated with excellent operative outcomes, and midterm follow-up suggests that the technique is durable. Longer term follow-up is needed to confirm continued stability of the aortic root. | Aortic Root Aneurysm |
The substantia innominata/lateral preoptic area (SI/LPO) is a subpallidal region which has been shown to regulate the hypermotility produced by drugs acting in the nucleus accumbens. Evidence has been presented that the SI/LPO contains glutamatergic nerve terminals and receptors for excitatory amino acids. The purpose of this study was to determine the effects of the activation of excitatory amino acid receptors in the SI/LPO on locomotor activity following the direct injection of excitatory amino acids into this brain site. It was found that the bilateral injection of alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA), kainic acid, and N-methyl-D-aspartic acid into the SI/LPO produced marked dose-dependent stimulations of locomotor activity which resembled the effects of these agents after their injection into the nucleus accumbens. The effect, however, was bell-shaped in that at high doses, the locomotor activity values decreased from their peak values. The coinjection of gamma-glutamylaminomethylsulfonate (GAMS) with AMPA into the SI/LPO was found to inhibit the hypermotility response to AMPA at doses that were unable to produce a significant inhibition of the hypermotility responses to kainic acid or N-methyl-D-aspartic acid. The injection of 6,7-dinitroquinoxaline-2,3-dione (DNQX) into the SI/LPO inhibited the hypermotility responses to AMPA or kainic acid while having no significant inhibitory effect on N-methyl-D-aspartic acid stimulated locomotor activity. The injection of D-alpha-aminoadipic acid into the SI/LPO produced a significant inhibition of the hypermotility response produced by N-methyl-D-aspartic acid at a dose that did not produce a significant inhibition of the hypermotility response produced by AMPA.(ABSTRACT TRUNCATED AT 250 WORDS) | Ibotenic Acid |
Ellagic acid (EA), a natural polyphenol abundant in fruits and common in our diet, is under intense investigation for its chemopreventive activity resulting from multiple effects. EA inhibits topoisomerase II, but the effects on the human enzyme of urolithins, its monolactone metabolites, are not known. Therefore, the action of several synthetic urolithins toward topoisomerases II was evaluated, showing that polyhydroxylated urolithins, EA, and EA-related compounds are potent inhibitors of the alpha and beta isoforms of human topoisomerase II at submicromolar concentrations. Competition tests demonstrate a dose-dependent relationship between ATP and the inhibition of the enzyme. Docking experiments show that the active compounds bind the ATP pocket of the human enzyme, thus supporting the hypothesis that EA and polyhydroxylated urolithins act as ATP-competitive inhibitors of human topoisomerase II. | Topoisomerase II Inhibitors |
Until the advent of plastinated cadavers, few outside the medical professions have had firsthand experience with human corpses. Such opportunities are now available at the Body Worlds exhibits of Gunther von Hagens. After an overview of these exhibits, we explore visitor responses as revealed in comment books available upon exiting the exhibit. Cultural, philosophical, and religious issues raised in the comments serve as a microcosm of society at large. The conclusion considers the challenge of such exhibits in introducing the public to science education, notes the image of the body as machine-so prevalent in the West-reflected in visitor comments, and finds hope that the exhibits promote, for many visitors, a sense of community among all humankind. | Voyeurism |
The prevalence of obesity and associated diseases has reached pandemic levels. Obesity is often associated with overnutrition and a sedentary lifestyle, but clearly other factors also increase the susceptibility of metabolic disease states. Ancestral and direct exposures to environmental toxicants and altered nutrition have been shown to increase susceptibility for obesity and metabolic dysregulation. Environmental insults can reprogram the epigenome of the germline (sperm and eggs), which transmits the susceptibility for disease to future generations through epigenetic transgenerational inheritance. In this review, we discuss current evidence and molecular mechanisms for epigenetic transgenerational inheritance of obesity susceptibility. Understanding ancestral environmental insults and epigenetic transgenerational impacts on future generations will be critical to fully understand the etiology of obesity and to develop preventative therapy options. | DNA Methylation |
Type 2 familial partial lipodystrophy (FPLD2) is a laminopathic lipodystrophy due to pathogenic variants in the LMNA gene. Its rarity implies that it is not well-known. The aim of this review was to explore the published data regarding the clinical characterisation of this syndrome in order to better describe FPLD2. For this purpose, a systematic review through a search on PubMed until December 2022 was conducted and the references of the retrieved articles were also screened. A total of 113 articles were included. FPLD2 is characterised by the loss of fat starting around puberty in women, affecting limbs and trunk, and its accumulation in the face, neck and abdominal viscera. This adipose tissue dysfunction conditions the development of metabolic complications associated with insulin resistance, such as diabetes, dyslipidaemia, fatty liver disease, cardiovascular disease, and reproductive disorders. However, a great degree of phenotypical variability has been described. Therapeutic approaches are directed towards the associated comorbidities, and recent treatment modalities have been explored. A comprehensive comparison between FPLD2 and other FPLD subtypes can also be found in the present review. This review aimed to contribute towards augmenting knowledge of the natural history of FPLD2 by bringing together the main clinical research in this field." | Lipodystrophy, Familial Partial |
Amorphous solid dispersions of clotrimazole in the polymer Kollidon VA64 were prepared as films in concentrations from 0% to 100% in 10% by weight increments. Nanoindentation was performed on each film at 18% and 49% relative humidity to assess the effect of drug loading and humidity on the mechanical properties of the solid dispersions. Although the addition of clotrimazole to the polymer reduces the glass transition temperature of the system as measured by differential scanning calorimetry, the hardness, reduced elastic modulus, and storage modulus were found to increase to values greater than those of either pure component up to drug loadings of approximately 60% by weight. Further addition of clotrimazole to the system resulted in decreased hardness and moduli with increased drug load. Dynamic vapor sorption of the dispersions shows that the hygroscopicity of the system is reduced as clotrimazole is added to the polymer. | Clotrimazole |
Because of the widely held hypothesis that the Light" drinker and the "Heavy" drinker may respond differentially to various treatment programs, it appears of value to explore some of the basic differences between these two groups. Several hundred male drivers were studied prior to entering any one of several court-referred drinking-driver treatment programs in Orange County, California. One hundred sixty-nine "Light" drinkers and 112 "Heavy" drinkers were administered a biographical questionnaire, the Michigan Alcohol Screening Test, the Cornell Medical Index, and the Guilford-Zimmerman Temperament Survey. When compared with the "Light" drinker, the "Heavy" drinker tends to have stronger tendencies toward sociopathy, a lower educational level, and a greater tendency to not complete assigned treatment programs. Furthermore, they admit to a greater number of emotional and physical problems. These findings have implications for structuring the type of treatment program to which they may or may not respond. Since future research may indicate that the "Heavy" drinker is not responsive to existing treatment programs, we must consider the possibility of abandoning or restructuring most of our current programs if they prove not to be cost-effective." | Alcoholism |
It has been suggested that attention modulates the speed at which cues come to predict contingent outcomes, and that attention changes with the prediction errors generated by cues. Evidence for this interaction in humans is inconsistent, with divergent findings depending on whether attention was measured with eye fixations or learning speed. We included both measures in our experiment. Initially, predictive cues (A and B) were consistently followed by one outcome (o1), while nonpredictive cues (X and Y) were followed by two randomly alternating outcomes (o1 and o2). Consistent with an effect of prediction error, participants' fixated for longer on the nonpredictive cues than on the predictive ones. Then, the cues were combined in three pairs: AX, followed by o1, and AY and BX, followed by o2. Discrimination of AX and AY depended on the previously nonpredictive cues and, given that these received more attention during initial training, it should proceed faster than discrimination of AX and BX, which depended on the previously predictive cues. However, participants learned to predict the outcomes of AY and BX at a similar rate. The fixation times were similar for the previously predictive and previously nonpredictive cues. We discuss reasons that could explain these findings. | Cues |
A growing body of information suggests antigonadotropic and atretogenic roles for granulosa cell-derived insulin-like growth factor binding proteins (IGFBPs) 4 and 5 during ovarian folliculogenesis. Activation of protein kinase-A (PKA) in rat granulosa cells has been shown to modulate the relative expression of IGFBP-4 and -5 transcripts and proteins. In this article, we assess the role of protein kinase-C (PKC) in this regard. Provision of granulosa cells with phorbol 12-myristate 13-acetate (PMA) (but not 4alphaPMA, an inert analogue), a tumor-promoting phorbol ester and an established activator of PKC, was without significant effect on the expression of IGFBP-4 transcripts but resulted in biphasic dose-dependent alterations in IGFBP-5 transcripts and in the accumulation of the IGFBP-4 and -5 proteins. Comparable effects were noted for GnRH, an established PKC agonist. Provision of staurosporine, a potent inhibitor of the catalytic subunit of PKC, produced significant dose-dependent decrements in the relative expression of IGFBP-5 transcripts. Treatment with FSH (presumptively PKA-mediated) markedly attenuated the ability of PMA or GnRH to upregulate the accumulation of the IGFBP-5 (but not IGFBP-4) protein. Taken together, our present findings indicate that the modulation of rat ovarian IGFBP-4 and -5 is PKC as well as PKA dependent and that these two signaling pathways interact in a diametrically opposed and antagonistic fashion." | Insulin-Like Growth Factor Binding Protein 5 |
Females homozygous for the Purkinje cell degeneration mutation (pcd) are fertile, although the success rate is much lower than in the wild type. We performed detailed analysis of reproductive abnormalities of pcd females. The number of oocytes produced following exogenous gonadotropin treatment was much lower in pcd3J-/- females than in pcd3J+/+ females. Furthermore, the estrous cyclicity of pcd3J-/- females according to the appearance of the vagina was almost undetectable comparing to that of the wild type. Histological analyses and follicle counting of 4- and 8-week-old pcd3J-/- ovaries showed an increase in the number of secondary follicles and a decrease in the number of antral follicles, indicating that AGTPBP1/ CCP1 plays an important role in the development of secondary follicles into antral follicles. Consistent with a previous analysis of the pcd cerebellum, pcd3J-/- ovaries also showed a clear increase in the level of polyglutamylation. Gene expression analysis showed that both oocytes and cumulus cells express CCP1. However, Ccp4 and CCP6, which can compensate the function of CCP1, were not expressed in mouse ovaries. Failure of microtubule deglutamylation did not affect the structure and function of the meiotic spindle in properly aligning chromosomes in the center of the nucleus during meiosis in pcd3J-/- females. We also showed that the pituitary-derived growth and reproduction-related endocrine system functions normally in pcd3J-/- mice. The results of this study provide insight into additional functions of CCP1, which cannot be fully explained by the side chain deglutamylation of microtubules alone." | Serine-Type D-Ala-D-Ala Carboxypeptidase |
Chronic headache is a significant public health problem in Western nations. Although controlled trials demonstrate the efficacy and cost-effectiveness of face-to-face behavioral therapy, most headache sufferers have limited access to these treatments. Delivery of behavioral interventions using Internet technology has the potential to reach a larger number of headache sufferers and reduce the burden of disease. This randomized controlled study evaluated an Internet-delivered behavioral regimen composed of progressive relaxation, limited biofeedback with autogenic training, and stress management versus a symptom monitoring waitlist control. Treatment led to a significantly greater decrease in headache activity than symptom monitoring alone. Thirty-nine percent of treated individuals showed clinically significant improvement on self-report measures of headache symptoms at post-treatment. At two-month follow-up, 47% of participants maintained improvement. Treatment had a significant impact on general headache symptoms and headache-related disability. There was a 35% within-group reduction of medication usage among the treated subjects. The Internet program was more time-efficient than traditional clinical treatment. Treatment and follow-up dropout rates, 38.1% and 64.8%, respectively, were typical of behavioral self-help studies. This approach to self-management of headache is promising; however, several methodological and ethical challenges need to be addressed. | Autogenic Training |
Tobacco necrosis virus (TNV-D) has a plus-strand RNA genome that is neither 5' capped nor 3' poly-adenylated. Instead, it utilizes a 3' cap-independent translational enhancer (3'CITE) located in its 3' untranslated region (UTR) for translation of its proteins. We have examined the protein expression strategies used by TNV-D and our results indicate that: (i) a base pairing interaction between conserved ACCA and UGGU motifs in the genomic 5'UTR and 3'CITE, respectively, is not required for efficient plant cell infection, (ii) similar potential 5'UTR-3'CITE interactions in the two viral subgenomic mRNAs are not needed for efficient translation of viral proteins in vitro, (iii) a small amount of capsid protein is translated from the viral genome by a largely 3'CITE-independent mechanism, (iv) the larger of two possible forms of capsid protein is efficiently translated, and (v) p7b is translated from subgenomic mRNA1 by a leaky scanning mechanism. | Tombusviridae |
BACKGROUND AND OBJECTIVES: Although anxiety consists of multiple components, including cognitive, affective, motivational, and physiological, and some findings suggest that there might be differences regarding their control antecedents and effects on performance, previous studies have largely neglected to examine these components separately and for reasons of convenience often assessed test anxiety as a unified construct using a single-item. Therefore, this study investigated the different test anxiety components with the goal to: (1) examine the relative impact of the anxiety components in the mediating mechanism that connects control and performance - as proposed by Pekrun's control-value theory, and (2) determine which specific anxiety component is underlying common single-item anxiety measures. METHODS: The research questions were investigated using an intra-individual approach in a sample of N = 137 German 8th graders during a mathematics exam. RESULTS: As expected, control was negatively related to all anxiety components, but associations varied in strength. Additionally, the components differed in their relative impact on performance, with the cognitive component being central for this outcome. Furthermore, common single-item measures seem to specifically assess the affective component, and thus not the component most relevant for test performance. CONCLUSION: Consequently, our study strongly recommends to distinguish between the anxiety components depending on the research question at hand. | Test Anxiety |
Orthodontic tooth movement occurs in six degrees of freedom, which includes opening and closing spaces. Traditionally, opening and closing spaces are achieved with auxiliaries such as power chains or springs because all traditional bracket systems cannot achieve this tooth movement by themselves. The InBrace system has the capability to program tooth movement in all six degrees of freedom, including opening and closing spaces, through digital customization and its use of Programmed Non-Sliding Mechanics. | Orthodontic Appliances |
Radiostereometric analysis (RSA) is routinely implemented with two paired Roentgen tubes for three-dimensional (3D) implant migration measurements. A conventional set-up of one stationary tube and one mobile could be time-consuming. Utilizing two customized ceiling-mounted tubes is normally associated with investment costs. Thus, a pilot set-up of a motorized system (single Roentgen source) for radiostereometric image acquisition may be a time-saving and space-efficient alternative. RSA using the motorized system is feasible in this study as a non-synchronized image acquisition technique, however, patient motion may occur and influence the assessment of implant migration. The phantom study aimed to assess accuracy of RSA using the motorized Roentgen system in this in vitro study. Accuracy values of translations and rotations were +/-0.29 mm and +/-0.48 degrees for the single Roentgen source RSA set-up and +/-0.26 mm and +/-0.48 degrees for the conventional RSA set-up. This study was also performed to simulate potential patient motion during exposure intervals between paired image acquisition. RSA using the motorized system is able to implement RSA with acceptable accuracy. In general, RSA with synchronized image acquisition is the gold standard to access in vivo implant migration with the highest accuracy. Patient motion exists in non-synchronized image acquisition techniques and results in RSA-related motion artifacts. Then we introduced what RSA-related motion artifacts are. The uniplanar calibration cage applied in the study has a few fiducial and control markers, and some of the markers were occluded in radiographs. Whereas, the number of markers in the calibration cage is correlated with accuracy of 3D implant reconstruction. | Radiostereometric Analysis |
The roots of Rauwolfia volkensii yielded 26 alkaloids comprising five main groups--sarpagan, akuammicine, heteroyohimbine with derived oxindole and anhydronium bases, yohimbine with 18-hydroxy-yohimbine and its derived esters, and dihydroindole alkaloids. The principal alkaloids were ajmaline (0.08 per cent) and reserpiline (0.15 per cent), and the reserpine yield (0.0007 per cent) was very low. | Rauwolfia |
Tricyclic (T) guanine analogues are a class of compounds in which the N1 and N(2) atoms of the guanine system are linked by etheno bridge to form the 3,9-dihydro-9-oxo-5H-imidazo[1,2-a]purine system. Almost 70 tricyclic derivatives of guanine-type potent antiherpetic agents acyclovir (ACV), ganciclovir (GCV) and 9-[cis-1',2'-bis(hydroxymethyl)cycloprop-1'-yl]methylguanine were synthesized and evaluated for activity against viruses of the herpes family. Here, we review the most successful compounds in terms of their antiviral activity and physico-chemical properties. These features are modulated by the kind and position of additional substituents present in the appended third ring of aglycone. The best antiherpetic activity-fluorescence combinations as well as activity of compounds in comparison to parent congeners are summarized. The data presented indicate that compounds of the 6-(4-RPh) family are of particular importance because of their advantageous antiviral potency, increased lipophilicity and good or moderate fluorescence properties. | Acyclovir |
In preparation for tracheal intubation during induction of anesthesia, the patient may be ventilated with 100% oxygen. To investigate the impact of acute isocapnic hyperoxia on endothelial activation and vascular remodeling, ten healthy young men (24+/-3 years) were exposed to 5-min normoxia (21% O2) and 10-min hyperoxia trials (100% O2). During hyperoxia, intercellular adhesion molecules (ICAM-1) (hyperoxia: 4.16+/-0.85 vs normoxia: 3.51+/-0.84 ng/mL, P=0.04) and tissue inhibitor matrix metalloproteinase 1 (TIMP-1) (hyperoxia: 8.40+/-3.84 vs normoxia: 5.73+/-2.15 pg/mL, P=0.04) increased, whereas matrix metalloproteinase (MMP-9) activity (hyperoxia: 0.53+/-0.11 vs normoxia: 0.68+/-0.18 A.U., P=0.03) decreased compared to the normoxia trial. We concluded that even short exposure to 100% oxygen may affect endothelial activation and vascular remodeling. | Vascular Remodeling |
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