The Effect of Educational Intervention Based on BASNEF Model on Self-Medication Behavior of Type 2 Diabetic Patients.
Diabetes is one of the main reasons of the increase of morbidity and mortality around the world. Considering the burden of disease, self-medication can result in irrecoverable consequences. The aim of this study is to investigate the effect of educational intervention based on Beliefs, Attitudes, Subjective Norms and Enabling Factors (BASNEF) model on self-medication behaviors of type 2 diabetic patients in Fasa, Fars province, Iran, in 2017-2018. In this quasi-experimental study, 200 type 2 diabetic patients under cover of the diabetes center of Fasa were investigated (100 patients for experimental group and 100 patients for control group). A questionnaire investigating demographic information and BASNEF Model constructs (knowledge, attitude, enabling factors, subjective norms, and behavioral intention) was used for evaluating self-medication behaviors of patients before and 3 months after intervention. The average age of experimental group was 53.25 ± 8.42 and the average age of control group was 54.18 ± 8.13. Three months after intervention, experimental group showed significant enhancement in knowledge, attitude, enabling factors, subjective norms, and behavioral intention and their self-medication behaviors reduced, while control group showed no significant changes in mentioned factors. The present study indicated the efficiency of BASNEF model on reduction of self-medication behaviors of diabetic patients. Hence, this model can act as a framework for designing and implementing educational interventions in this field.


Sporadic breast carcinomas with somatic BRCA1 gene deletions share genotype/phenotype features with familial breast carcinomas.
High frequencies of loss of heterozygosity (LOH) are found in familial breast carcinomas with BRCA mutations. Although LOH of BRCA1 does not coincide with somatic BRCA1 mutations, reduced BRCA1 protein expression and hypermethylation indicate the involvement of BRCA1 in sporadic carcinogenesis. To further investigate the role of BRCA we determined LOH of BRCA1 and correlated this with LOH in other breast cancer-associated regions. A total of 105 sporadic breast carcinomas were analysed for LOH in the regions of BRCA1, BRCA2, TP53, Caveolin1, "putative BRCA3", PTEN, ATM and E-cadherin and correlated it with clinicopathological features. We found an overall increase of LOH in carcinomas with simultaneous LOH of BRCA1. Significantly higher LOH rates were detected in the regions of TP53 (80%: 34.7%; p<0.005), 8q21 (72.7%: 30.6%; p<0.010) and 10q22-23 (21.1%: 5.9%; p=0.043). Moreover, estrogen receptor-negative carcinomas revealed LOH of BRCA1 more frequently than estrogen receptor-positive carcinomas (39%: 12%; p=0.003). These data indicate that LOH of BRCA1 coincides with a defect of the DNA repair pathway. Therefore, LOH of BRCA1 determines a subgroup of sporadic breast carcinomas sharing genotype/phenotype features with familial breast carcinomas.


Communicating with patients who have hearing loss.
Access to health care services is of paramount interest to all New Jerseyans. For people with varying degrees of hearing loss, affordable health insurance, while important, is not the only barrier to quality health care. Doctors are required by law to ensure effective communication between themselves and their deaf or hard-of-hearing patients.


Fungal community composition in neotropical rain forests: the influence of tree diversity and precipitation.
Plant diversity is considered one factor structuring soil fungal communities because the diversity of compounds in leaf litter might determine the extent of resource heterogeneity for decomposer communities. Lowland tropical rain forests have the highest plant diversity per area of any biome. Since fungi are responsible for much of the decomposition occurring in forest soils, understanding the factors that structure fungi in tropical forests may provide valuable insight for predicting changes in global carbon and nitrogen fluxes. To test the role of plant diversity in shaping fungal community structure and function, soil (0-20 cm) and leaf litter (O horizons) were collected from six established 1-ha forest census plots across a natural plant diversity gradient on the Isthmus of Panama. We used 454 pyrosequencing and phospholipid fatty acid analysis to evaluate correlations between microbial community composition, precipitation, soil nutrients, and plant richness. In soil, the number of fungal taxa increased significantly with increasing mean annual precipitation, but not with plant richness. There were no correlations between fungal communities in leaf litter and plant diversity or precipitation, and fungal communities were found to be compositionally distinct between soil and leaf litter. To directly test for effects of plant species richness on fungal diversity and function, we experimentally re-created litter diversity gradients in litter bags with 1, 25, and 50 species of litter. After 6 months, we found a significant effect of litter diversity on decomposition rate between one and 25 species of leaf litter. However, fungal richness did not track plant species richness. Although studies in a broader range of sites is required, these results suggest that precipitation may be a more important factor than plant diversity or soil nutrient status in structuring tropical forest soil fungal communities.


Whole genome sequencing and complete genetic analysis reveals novel pathways to glycopeptide resistance in Staphylococcus aureus.
The precise mechanisms leading to the emergence of low-level glycopeptide resistance in Staphylococcus aureus are poorly understood. In this study, we used whole genome deep sequencing to detect differences between two isogenic strains: a parental strain and a stable derivative selected stepwise for survival on 4 µg/ml teicoplanin, but which grows at higher drug concentrations (MIC 8 µg/ml). We uncovered only three single nucleotide changes in the selected strain. Nonsense mutations occurred in stp1, encoding a serine/threonine phosphatase, and in yjbH, encoding a post-transcriptional negative regulator of the redox/thiol stress sensor and global transcriptional regulator, Spx. A missense mutation (G45R) occurred in the histidine kinase sensor of cell wall stress, VraS. Using genetic methods, all single, pairwise combinations, and a fully reconstructed triple mutant were evaluated for their contribution to low-level glycopeptide resistance. We found a synergistic cooperation between dual phospho-signalling systems and a subtle contribution from YjbH, suggesting the activation of oxidative stress defences via Spx. To our knowledge, this is the first genetic demonstration of multiple sensor and stress pathways contributing simultaneously to glycopeptide resistance development. The multifactorial nature of glycopeptide resistance in this strain suggests a complex reprogramming of cell physiology to survive in the face of drug challenge.


Recovery of DNA sequences flanking P-element insertions in Drosophila: inverse PCR and plasmid rescue.
The Drosophila melanogaster P-transposable element is a powerful and widely used research tool. Sequences flanking the P-element can be recovered and the site of insertion can be mapped to the nucleotide, to connect the genetic and physical maps and facilitate molecular analysis of the gene of interest. The Berkeley Drosophila Genome Project (BDGP) has assembled a well-characterized collection of lethal mutations induced by single P-element insertions generated by a number of laboratories. The genomic DNA sequences adjacent to these insertions have been recovered by either plasmid rescue or inverse polymerase chain reaction (PCR). The combination of a complete genomic DNA sequence and relatively fast and easy molecular methods for mapping P-element insertion sites to the nucleotide enhances the use of P-elements as tools in Drosophila research. This protocol provides detailed procedures for isolating DNA flanking P-element insertions.


Adjuvant treatment for renal cell carcinoma.
Despite significant advances in the diagnosis, staging and treatment of patients with renal cell carcinoma, recurrence rates following surgical resection of locally aggressive tumours remain high. In an effort to delay disease progression and improve survival, the concept of adjuvant therapy has been proposed. Optimal adjuvant therapy for surgically resected renal cell carcinoma remains to be defined and the evaluation of adjuvant therapies will require properly controlled and adequately powered randomised trials. Promising preliminary results have been seen with active immunotherapies and agents that target critical signalling pathways, and there are several Phase III trials of these novel treatment options that are underway. In addition, classification of patients into high- and low-risk subgroups on the basis of a prognosis profile will serve as a useful means to guide clinicians in improving the selection of patients who are likely to derive benefit from adjuvant therapy. This will lead to a future area of investigation, which will be the identification of patients within the target population that should respond to a given treatment. This review will discuss the role and current status of adjuvant therapies for renal cell carcinoma.


NaxD is a deacetylase required for lipid A modification and Francisella pathogenesis.
Modification of specific Gram-negative bacterial cell envelope components, such as capsule, O-antigen and lipid A, are often essential for the successful establishment of infection. Francisella species express lipid A molecules with unique characteristics involved in circumventing host defences, which significantly contribute to their virulence. In this study, we show that NaxD, a member of the highly conserved YdjC superfamily, is a deacetylase required for an important modification of the outer membrane component lipid A in Francisella. Mass spectrometry analysis revealed that NaxD is essential for the modification of a lipid A phosphate with galactosamine in Francisella novicida, a model organism for the study of highly virulent Francisella tularensis. Significantly, enzymatic assays confirmed that this protein is necessary for deacetylation of its substrate. In addition, NaxD was involved in resistance to the antimicrobial peptide polymyxin B and critical for replication in macrophages and in vivo virulence. Importantly, this protein is also required for lipid A modification in F. tularensis as well as Bordetella bronchiseptica. Since NaxD homologues are conserved among many Gram-negative pathogens, this work has broad implications for our understanding of host subversion mechanisms of other virulent bacteria.


The social skill difficulties of young adults with physical disabilities.
Adolescence is generally considered to be a time of increased social activity and the rapid expansion of a teenager's social circle. By contrast, a young person with a physical disability is likely to lack social independence, become socially isolated and experience difficulties in maintaining social relationships. The present study indicates that while both able-bodied and physically disabled young people experience difficulties in social situations, those with physical disabilities experience difficulties that are more severe in nature. Overall, 75% of the disabled group and 70% of the comparison group experienced difficulties in social situations. However, 37% of the disabled group experienced difficulties that were severe in nature compared to only 3% of the comparison group. Whilst these problems are of sufficient magnitude to warrant intervention, programmes of social skills training for people with physical disabilities are not yet generally available. It is recommended that training programmes in social skills should be made available to teenagers with physical disabilities.


Pentraxin-3 Levels Relate to the Wells Score and Prognosis in Patients with Acute Pulmonary Embolism.
To investigate the value of the PTX-3 test in evaluating the prognosis of acute pulmonary embolism (APE). 117 APE patients were selected and divided into two groups according to plasma PTX-3 levels, including the group in which PTX - 3 ≥ 3.0 ng/mL (n = 42) and the group in which PTX - 3 < 3.0 ng/mL (n = 75). Patients were stratified into high-risk, medium-risk, and low-risk groups according to the Wells scores, and the PTX-3 levels were compared among the groups. Patients had been followed-up as well. According to the Wells scores, 11 patients were classified as high-risk (9.4%) and 68 were medium-risk (58.1%), while 38 were low-risk (32.5%). The PTX-3 levels in different risk groups were statistically different (all P < 0.05). During the follow-up period, 6 deaths occurred in the group with elevated PTX-3 (≥3.0 ng/mL), while 2 deaths occurred in the group with nonelevated PTX-3 (<3.0 ng/mL). The difference between the two groups was statistically significant (P < 0.01). 13 patients were hospitalized due to recurrent pulmonary embolism, of which 12 were in the group with elevated PTX-3 (≥3.0 ng/mL), while 1 patient was in the group with nonelevated PTX-3 (<3.0 ng/mL). The difference was statistically significant (P < 0.01). The plasma PTX-3 level in APE patients is correlated with PE risk stratification. There is a significant correlation between PTX-3 levels and PE-related cardiac deaths, as well as the prognosis of recurrent PE. PTX-3 can be used as a clinical indicator of PE prognosis.


Thunberga gen. nov., a new genus of huntsman spiders from Madagascar <br />(Araneae: Sparassidae: Heteropodinae).
A new genus of the family Sparassidae is described from Madagascar: Thunberga gen. nov. It can be distinguished from other genera of the Heteropodinae by its different cheliceral dentition and eye arrangement as well as by its uniquely dotted prosoma. Four species are transferred to the new genus: T. hildebrandti (Järvi, 1912) comb. nov. (from Rhitymna Simon, 1897a), T. malagassa (Strand, 1907) comb. nov. (from Olios Walckenaer, 1837), T. nossibeensis (Strand, 1907) comb. nov. (from Olios), T. septifer (Strand. 1908) comb. nov. (from Olios, elevated to species rank). T. hildebrandti comb. nov. is recognised as junior synonym of T. nossibeensis comb. nov. One species is described for the first time: Thunberga greta spec. nov. (female, Madagascar). The systematic placement within the family and the character "anterior epigynal pocket" are discussed.


Genetic activity profiles in the testing and evaluation of chemical mixtures.
Some knowledge of the potential genetic activity of a complex environmental mixture may be gained from an assessment of the genetic activity of its component chemicals. The expanded Genetic Activity Profile (GAP) data base provides a computer-generated graphic representation of genetic bioassay data as a function of dose of the substance tested. In addition, the Atmospheric Chemical Compound (ACC) data-base contains information on chemical structures, properties, detection methods, and sources of chemicals found in ambient air. Using the combined data bases, the quantity of an individual chemical present within a mixture or fraction of a mixture may be related to the quantity (lowest effective dose, LED) of the chemical, by itself, required to demonstrate a positive response in one or more genetic bioassays.


Persistence of genetically altered fields in head and neck cancer patients: biological and clinical implications.
In 1953, Slaughter et al. [D. P. Slaughter et al., Cancer (Phila.), 6: 963-968, 1953] proposed the concept of field cancerization in patients with squamous cell carcinoma of the head and neck (HNSCC) and discussed its clinical significance for the development of second primary tumors and local recurrences. To define the process of field cancerization and its putative clinical implications, we analyzed genetic aberrations in HNSCC and the accompanying macroscopically normal mucosa. In 28 HNSCC patients, loss of heterozygosity was determined in tumor and five noncontiguous mucosal biopsies using eight microsatellite markers at 9p, 3p, and 17p. For patients who showed loss of heterozygosity in their mucosal biopsies, all margins of the surgical specimen were subsequently analyzed to determine the extension of the field. In these cases, additional markers at 8p, 13q, and 18q as well as p53 mutations were included to determine subclonal differences between field and tumor. Genetically altered fields were detected in 36% (10 of 28) of the HNSCC patients. The field varied in size between patients and consisted of genetically different subclones. In 7 of 10 cases, the field extended into the surgical margins. One particular patient with a genetically altered field in a surgical margin developed a local recurrence after 28 months of follow-up. Microsatellite analysis showed that this recurrence had more molecular markers in common with the nonresected premalignant field than with the original tumor, suggesting that this persistent field has progressed further into a new malignancy. Our data show that genetically altered mucosa remains after treatment in a significant proportion of HNSCC patients, which may explain in part the high frequency of local recurrences and second primary tumors. Adequate identification and risk assessment of these genetically altered fields may have profound implications for future patient management.


Intramammary Metastasis in a Patient with a History of Renal Cell Carcinoma: A Case Report.
Intramammary metastasis of renal cell carcinoma (RCC) is extremely rare, accounting for only 1.5% of all intramammary metastases. Distinguishing intramammary metastases from benign tumors and breast cancer is clinically problematic. Some patients undergo excessive surgery after a misdiagnosis of breast cancer instead of a mammary tumor. We performed a core needle biopsy (CNB) of a breast mass that developed in a 71-year-old woman after surgeries for bilateral RCC and breast cancer, leading to a diagnosis of intramammary metastasis of RCC. In this case, the CNB and immunohistochemical examination were critical for reaching a definitive diagnosis. We conclude that, when examining patients with mammary tumors, establishing their history of malignant tumors may help diagnose intramammary metastasis and select the best treatment strategy.


Stage-dependent biomarker changes in spinocerebellar ataxia type 3.
Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3) is the most common autosomal dominant ataxia. In view of the development of targeted therapies for SCA3, precise knowledge of stage-dependent fluid and MRI biomarker changes is needed. We analyzed cross-sectional data of 292 SCA3 mutation carriers including 57 pre-ataxic individuals, and 108 healthy controls from the European Spinocerebellar ataxia type 3/Machado-Joseph Disease Initiative (ESMI) cohort. Blood concentrations of mutant ATXN3 and neurofilament light (NfL) were determined, and volumes of pons, cerebellar white matter (CWM) and cerebellar grey matter (CGM) were measured on MRI. Mutant ATXN3 concentrations were high before and after ataxia onset, while NfL continuously increased and deviated from normal 11.9 years before onset. Pons and CWM volumes decreased, but the deviation from normal was only 2.0 years (pons) and 0.3 years (CWM) before ataxia onset. We propose a staging model of SCA3 that includes an initial asymptomatic carrier stage followed by the biomarker stage defined by absence of ataxia, but a significant rise of NfL. The biomarker stage leads into the ataxia stage, defined by manifest ataxia. The present analysis provides a robust framework for further studies aiming at elaboration and differentiation of the staging model of SCA3.


CpG stimulation of chronic lymphocytic leukemia cells induces a polarized cell shape and promotes migration in vitro and in vivo.
In order to accomplish their physiological functions leukocytes have the capability to migrate. As a prerequisite they need to adopt a polarized cell shape, forming a leading edge at the front and a uropod at rear pole. In this study we explored the capability of chronic lymphocytic leukaemia (CLL) cells to adopt this leukocyte-specific migration phenotype. Furthermore, we studied the impact of the Toll-like receptor 9 (TLR9) agonists CpGs type A, B and C and the antagonist oligodesoxynucleotide (ODN) INH-18 on the cell polarization and migration process of primary human CLL cells. Upon cultivation, a portion of purified CLL cells adopted polarized cell shapes spontaneously (range 10-38%). Stimulation with CpG ODNs type B (ODN 2006) and CpGs type C (ODN 2395) significantly increased the frequency of morphologically polarized CLL cells, while ODN INH-18 was hardly able to act antagonistically. Like in human hematopoietic stem and progenitor cells, in morphologically polarized CLL cells CXCR4 was redistributed to the leading edge and CD50 to the uropod. Coupled to the increased frequencies of morphologically polarized cells, CpGs type B and C stimulated CLL cells showed higher migration activities in vitro and following intravenous injection higher homing frequencies to the bone marrow of immunocompromised NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice. Thus, presumably independent of TLR-9 signaling, CpGs type B and C promote the cellular polarization process of CLL cells and their ability to migrate in vitro and in vivo.


Thermodynamic Relationships for Perfectly Elastic Solids Undergoing Steady-State Heat Flow.
Available data on insulating, semiconducting, and metallic solids verify our new model that incorporates steady-state heat flow into a macroscopic, thermodynamic description of solids, with agreement being best for isotropic examples. Our model is based on: (1) mass and energy conservation; (2) Fourier's law; (3) Stefan-Boltzmann's law; and (4) rigidity, which is a large, yet heretofore neglected, energy reservoir with no counterpart in gases. To account for rigidity while neglecting dissipation, we consider the ideal, limiting case of a perfectly frictionless elastic solid (PFES) which does not generate heat from stress. Its equation-of-state is independent of the energetics, as in the historic model. We show that pressure-volume work (PdV) in a PFES arises from internal interatomic forces, which are linked to Young's modulus (Ξ) and a constant (n) accounting for cation coordination. Steady-state conditions are adiabatic since heat content (Q) is constant. Because average temperature is also constant and the thermal gradient is fixed in space, conditions are simultaneously isothermal: Under these dual restrictions, thermal transport properties do not enter into our analysis. We find that adiabatic and isothermal bulk moduli (B) are equal. Moreover, Q/V depends on temperature only. Distinguishing deformation from volume changes elucidates how solids thermally expand. These findings lead to simple descriptions of the two specific heats in solids: ∂ln(cP)/∂P = -1/B; cP = nΞ times thermal expansivity divided by density; cP = cVnΞ/B. Implications of our validated formulae are briefly covered.


Intramuscular atypical lipomatous tumor/well-differentiated liposarcoma of the pectoralis major masquerading as a breast tumor: management and review of the literature.
Atypical lipomatous tumor (ALT)/well-differentiated liposarcoma (WDL) of the pectoralis major muscle is an exceedingly rare clinical entity. We describe here a case of intramuscular ALT/WDL of the pectoralis major muscle in a female patient who presented with clinical manifestations of a rapidly growing breast tumor. Diagnostic evaluation and management of the patient are discussed along with a review of the relevant literature. We conclude that although the clinical examination may be inconclusive, the mammogram and especially the magnetic resonance imaging scan can precisely delineate the anatomic location and extent of the ALT/WDL of the pectoralis major muscle, thus allowing a correct preoperative diagnosis and adequate preoperative surgical planning. Complete resection is the treatment of choice for ALT/WDL. Long-term follow-up, however, remains mandatory because of the risk of local recurrence or delayed dedifferentiation.


Graduate Nurse Educator Students' Perceptions of the Use of Narrative Pedagogy in Online Learning: A Pilot Study.
This pilot study explored graduate nurse educator students' perceptions of the application of narrative pedagogy in an online environment. Four major themes were identified in 15 student discussion posts: adapting challenges, increasing digital human interactions, enabling strategies, and creating a partnership for learning. Results illustrate how integrating narrative pedagogy into online classes enables a transformation of student thinking and learning by providing alternate ways for nurse educators to promote active learning.


Subtype-specific regulation of the expression and function of muscarinic acetylcholine receptors in embryonic chicken retinal cells.
We examined the effect of long-term agonist exposure on muscarinic acetylcholine receptor expression and function in embryonic chicken retinal cells. Long-term carbachol exposure induced a time- and concentration-dependent decrease in M2, M3 and M4 muscarinic receptor numbers. Kinetic analyses revealed a first-order process with similar rate constants for all three subtypes. Both the maximal decrease and the agonist potency for regulation of M3 were significantly higher than those for M2 and M4. Upon agonist removal, M2 and M4 numbers returned to control values, but M3 recovery after 24 h was no higher than 40%. Agonist treatment did not alter the levels of receptor mRNAs. Receptor inactivation with a covalent alkylating antagonist demonstrated that the partial M3 protein recovery was not due to a decreased intrinsic basal rate of synthesis, suggesting that it is induced by agonist treatment. Prolonged carbachol exposure induced concomitant decreases in muscarinic-mediated inhibition of cyclic AMP accumulation which were completely reversed after agonist removal. Sustained receptor activation also promoted significant decreases in muscarinic receptor-stimulated phosphoinositide turnover, which were only partially reversed after agonist removal. These data demonstrate subtype-specific regulation of the expression and function of muscarinic receptors in the retina.


The effect of age on systemic absorption and systemic disposition of bupivacaine after subarachnoid administration.
In order to evaluate the role of the pharmacokinetics of the age-related changes in the clinical profile of spinal anesthesia with bupivacaine, we studied the influence of age on the systemic absorption and systemic disposition of bupivacaine after subarachnoid administration in 20 male patients (22-81 yr), ASA Physical Status 1 or 2, by a stable isotope method. After subarachnoid administration of 3 ml 0.5% bupivacaine in 8% glucose, a deuterium-labeled analog (13.4 mg) was administered intravenously. Blood samples were collected for 24 h. Plasma concentrations of unlabeled and deuterium-labeled bupivacaine were determined with a combination of gas chromatography and mass fragmentography. Biexponential functions were fitted to the plasma concentration-time data of the deuterium-labeled bupivacaine. The systemic absorption was evaluated by means of deconvolution. Mono- and biexponential functions were fitted to the data of fraction absorbed versus time. The maximal height of analgesia and the duration of analgesia at T12 increased with age (r = 0.715, P less than 0.001; r = 0.640, P less than 0.01, respectively). In 18 patients the systemic absorption of bupivacaine was best described by a biexponential equation. The half-life of the slow systemic absorption process (r = -0.478; P less than 0.05) and the mean absorption time (r = -0.551; P less than 0.02) decreased with age. The total plasma clearance decreased with age (r = -0.650, P less than 0.002), whereas the mean residence time and terminal half-life increased with age (r = 0.597, P less than 0.01; r = 0.503, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Wildfire risk management on a landscape with public and private ownership: who pays for protection?
Wildfire, like many natural hazards, affects large landscapes with many landowners and the risk individual owners face depends on both individual and collective protective actions. In this study, we develop a spatially explicit game theoretic model to examine the strategic interaction between landowners' hazard mitigation decisions on a landscape with public and private ownership. We find that in areas where ownership is mixed, the private landowner performs too little fuel treatment as they "free ride"-capture benefits without incurring the costs-on public protection, while areas with public land only are under-protected. Our central result is that this pattern of fuel treatment comes at a cost to society because public resources focus in areas with mixed ownership, where local residents capture the benefits, and are not available for publicly managed land areas that create benefits for society at large. We also find that policies that encourage public expenditures in areas with mixed ownership, such as the Healthy Forest Restoration Act of 2003 and public liability for private values, subsidize the residents who choose to locate in the high-risk areas at the cost of lost natural resource benefits for others.


ATPase activity in cells of the yeast Saccharomycopsis fibuligera during mycelial growth.
Levels of ATPase activity were examined in the cells of Saccharomycopsis fibuligera during mycelial growth. The mycelial cells (M-form cells) grown under standing culture conditions exhibited a marked increase of ATPase activity after 3 days, showing a broad peak between 5 and 20 days and a maximum at 10 days. The dry weight/ml of the yeast-like cells (Y-form cells) grown under shaking culture conditions reached its peak after 3 days and remained constant throughout the 10 day period of observation. The dry weight/ml of the M-form cells under standing culture conditions exhibited its peak in 10-15 days and then gradually decreased. A very small amount of Y-form cells among the M-form cells under standing culture conditions, exhibited very low ATPase activity even in 10 days' incubation. In M-form cells, the particles increased in number during 20 days of incubation.


[Effects of a novel orally-active antiallergic drug, quinotolast (FK021), on airway clearance].
The effects of a novel antiallergic drug, quinotolast (FK021, sodium 5-(4-oxo-1-phenoxy-4H-quinolizine-3-carboxamido) tetrazolate monohydrate), on airway clearance was studied in comparison with those of tranilast (an orally-active antiallergic drug). FK021 (10 mg/kg, p.o.) did not influence the rabbit airway secretion, whereas tranilast (100 mg/kg, p.o.) caused a slight suppression. Neither FK021 (10(-10)-10(-5) g/ml) nor tranilast (10(-6), 10(-4) g/ml) had any effect on pulmonary surfactant secretion in rat type II pneumocytes. FK021 (10 mg/kg, p.o.) caused a significant increase in the mucociliary transport rate in quails, whereas tranilast (320 mg/kg, p.o.) had no effect. Antitussive effects were examined in normal guinea pigs and guinea pigs made bronchitic by an exposure to SO2. FK021 (10 mg/kg, p.o.) and tranilast (320 mg/kg, p.o.) significantly depressed the cough reflex induced by citric acid in normal animals. FK021 (32 mg/kg, p.o.), but not tranilast (320 mg/kg, p.o.), showed antitussive effects on citric acid-induced cough in bronchitic animals. These results suggest that FK021 may have favorable effects on expectoration and cough reflex observed in the patients with chronic obstructive pulmonary diseases such as asthma.


Galaxy evolution. Quasar quartet embedded in giant nebula reveals rare massive structure in distant universe.
All galaxies once passed through a hyperluminous quasar phase powered by accretion onto a supermassive black hole. But because these episodes are brief, quasars are rare objects typically separated by cosmological distances. In a survey for Lyman-α emission at redshift z ≈ 2, we discovered a physical association of four quasars embedded in a giant nebula. Located within a substantial overdensity of galaxies, this system is probably the progenitor of a massive galaxy cluster. The chance probability of finding a quadruple quasar is estimated to be ∼10(-7), implying a physical connection between Lyman-α nebulae and the locations of rare protoclusters. Our findings imply that the most massive structures in the distant universe have a tremendous supply (≃10(11) solar masses) of cool dense (volume density ≃ 1 cm(-3)) gas, which is in conflict with current cosmological simulations.


Effects of amount of intake and stage of forage maturity on urinary allantoin excretion and estimated microbial crude protein synthesis in the rumen of steers.
Using ruminally cannulated steers, we investigated how urinary allantoin excretion was related to variations in feed intake and stage of forage maturity. Further, different approaches were compared for predicting ruminal microbial crude protein (MCP) synthesis and its efficiency. Experimental diets were arranged in a replicated 3 x 3 Latin square design (experiment 1) and a 4 x 4 Latin square design (experiment 2). In experiment 1, a mixed diet [forage to concentrate, 68:32 on a dry matter (DM) basis] was fed at three intake levels corresponding to 1, 1.5 and 2 times maintenance energy requirements. In experiment 2, four silage-based diets were fed based on perennial ryegrass (Lolium perenneL.), which was harvested at four maturity stages. Both experiments demonstrated the influence of diet on microbial growth rate and by this on efficiency of MCP synthesis, although the magnitude of the effects differed between approaches used for estimating MCP. Linear functions satisfactorily characterised the relationship between urinary allantoin excretion (y) and digestible organic matter (OM) intake (x, kg/day; experiment 1: y = 7.94 + 17.34 x; R(2) = 0.785) or intake of OM effectively degraded in the rumen (x, kg/day; experiment 2; y = 22.32 + 5.93 x; R(2) = 0.695). Urinary excretion of allantoin permitted a semi-quantitative prediction of MCP synthesis: ranking of diets and magnitude of changes in MCP synthesis were reflected.


US FDA Modernization Act, section 114: uses, opportunities and implications for comparative effectiveness research.
Section 114 of the 1997 US FDA Modernization Act (FDAMA) is an important vehicle for pharmaceutical companies to promote the economic value of their drugs to formulary decision makers, but little is known about how the Section has been interpreted and used. We conducted a web-based survey of a convenience sample of 35 outcomes directors of major pharmaceutical and biotechnology companies. We asked them about their interpretation of, and experiences with, Section 114, as well as their views regarding the FDA's role in the matter, and whether the advent of comparative effectiveness research (CER) will affect the use of Section 114 promotions. Of the 35 experts, 16 (46%) completed the survey. 81% stated they always or frequently consider using Section 114 when making promotional claims for drugs. 75% stated that the FDA should issue guidance on how to make such promotions to payers, especially what qualifies as "healthcare economic information" and "competent and reliable scientific evidence." Most expected to use Section 114 to a greater extent in the future, and agreed that the increased focus on CER would increase Section 114 use. The survey suggests strong awareness about Section 114 among the outcomes directors and some use of the Section for promotional purposes. It also reflects a belief that CER will increase use of Section 114 promotions, and that guidance from the FDA is needed. More clarity - and, ideally, flexible interpretation - from the FDA is warranted, especially given the rise of CER.


Multiple mutations conferring ciprofloxacin resistance in Staphylococcus aureus demonstrate long-term stability in an antibiotic-free environment.
Two unrelated strains of Staphylococcus aureus, one with a single mutation in grlA, the other with multiple mutations in gyrA, gyrB, grlA, grlB, norA and the norA promoter region, encoding low-level and high-level ciprofloxacin resistance, respectively, were studied. The characterized mutations in these genes were conserved when both strains were passaged for at least 500 generations in an antibiotic-free environment. New, rapidly stabilized mutations and higher MICs were detected for strains passaged in sub-MIC ciprofloxacin concentrations. The seeming irreversibility of quinolone resistance may affect the long-term success of this drug class.


Flavonoids in the treatment of hypertension in geriatric patients
Geriatric patients belong to a group over 65 years old. In general these patients present multiple chronic diseases and impairments with disability, body mass diminished and generalized fatigue. On the other hand, a high percentage of these patients have cardiovascular diseases. For this reason, several studies suggest that associated with drugs treatment consumption of natural products such as flavonoids, contribute to improve the quality of life of geriatric patients. The aim of this work is to review in literature the effect of flavonoids in vascular protection of older adults. Literature review indicates that the intake of flavonoids significantly reduces the risk of hypertension and cardiovascular disease. Likewise, its consumption is associated with an improvement in endothelial function, since they act regulating different kinases like protein kinase B, nitric oxide synthase and the consequent synthesis of nitric oxide (NO), which leads to improve vasodilation. Finally, flavonoids also act to regulate the functioning of other kinases, phophodiesterases, ion channels diminishing vascular inflammation. Foods enriched in polyphenols improve endothelial function by promoting vascular dilation and lowering blood pressure.


Microstructure, rheological and water mobility behaviour of plant-based protein isolates (pea and quinoa) and locust bean gum mixtures.
This work reports the impact of locust bean gum (LBG) in the continuous phase of plant-based proteins, i.e. quinoa protein (QPI) and pea protein isolates (PPI). Experimental measurements such as confocal microscopy, rheological analysis and water mobility via nuclear magnetic resonance (nmr) spin-spin relaxation time (T2) were carried out. The influence of LBG on the rheological properties of QPI and PPI is consistent with an exchange-based nmr interpretation of T2 for biopolymer and water. Addition of LBG increased the viscoelastic properties (storage and loss modulus) and shear viscosities of the mixtures. LBG interacted with both plant proteins, resulting in the formation of more dense protein networks and protein coacervates. A stronger interaction between the PPI and LBG was observed, resulting in higher shear viscosities with lower water mobility as compared to QPI:LBG formulations. Results indicated that the interaction between the protein and polysaccharide played a significant role in the microstructure, its rheological properties and consequently water mobility.


From ureteric bud to the first glomeruli: genes, mediators, kidney alterations.
The development of the mammalian kidney is a complex and in part unknown process which requires interactions between pluripotential/stem cells, undifferentiated mesenchymal cells, epithelial and mesenchymal components, eventually leading to the coordinate development of multiple different specialized epithelial, endothelial and stromal cell types within the kidney architectural complexity. We will describe the embryology and molecular nephrogenetic mechanisms, a fascinating traffic of cells and tissues which takes place in five stages: (1) ureteric bud (UB) development; (2) cap mesenchyme formation; (3) mesenchymal-epithelial transition (MET); (4) glomerulogenesis and tubulogenesis; (5) interstitial cell development. In particular, we will analyze the multiple cell types involved in these dramatic events as characters moving between different worlds, from the mesenchymal to the epithelial world and back, and will start to define the multiple factors that propel these cells during their travels throughout the developing kidney. Moreover, according with the hypothesis of renal perinatal programing, we will present the results reached in the fields of immunohistochemistry and molecular biology, by means of which we can explain how a loss or excess of molecular factors governing nephrogenesis may cause the onset of pathologies of different gravity, in some cases leading to a chronic kidney disease at different times from birth.


The production and characterization of two monoclonal antibodies to rat kidney L-arginine: glycine amidinotransferase.
Rat kidney L-arginine:glycine amidinotransferase (transamidinase) has been purified previously to homogeneity as two fractions, designated alpha and beta. No differences in the properties of these two fractions could be found. Two monoclonal antibodies (Tran/NS-1/1 and Tran/NS-1/3) to the purified alpha fraction of rat kidney transamidinase were produced, purified, and characterized. The results of competitive binding studies of the two monoclonal antibodies to alpha transamidinase were as follows: 1) Tran/NS-1/3 had no effect on 125I-Tran/NS-1/1 binding while Tran/NS-1/1 inhibited 125I-Tran/NS-1/1 binding; 2) Tran/NS-1/3 inhibited 125I-Tran/NS-1/3 binding while Tran/NS-1/1 had no effect on 125I-Tran/NS-1/3 binding. Therefore, Tran/NS-1/1 and Tran/NS-1/3 bound to different antigenic determinants on alpha transamidinase. 125I-Tran/NS-1/1 and 125I-Tran/NS-1/3 each had high avidity constants (approximately 10(7)-10(9)) for both alpha and beta rat kidney transamidinase. Tran/NS-1/1 and Tran/NS-1/3 bound to human kidney transamidinase in ELISA assays. A quantitative immunosorbent inhibition assay for rat kidney transamidinase was developed with 125I-Tran/NS-1/3. Approximately 30 ng of immunoreactive transamidinase could be detected by this immunosorbent inhibition assay. The amount of Tran/NS-1/3 immunoreactive species in rat lung and testicular tissue by the immunosorbent inhibition assay correlated well with the amount of transamidinase activity found in those tissues. The availability of the monoclonal antibodies, Tran/NS-1/1 and Tran/NS-1/3, should facilitate studies of rat and human transamidinase structure and regulation.


Growth behavior and characteristics of one dimensional ZnO nanostructures by metalorganic chemical vapor deposition.
The ZnO nanorods have been grown on silicon substrates by a metalorganic chemical vapor deposition (MOCVD) process with/without Au catalytic layer. The growth behavior of ZnO nanorods changed with the catalytic layer. The presence of Au catalyst complicated the growth direction of ZnO nanorods in the MOCVD methods. The ZnO nanorods had single crystalline atomic structure and pure compositions without impurities and strong and narrow excitonic emission. We investigated the growth behavior of the ZnO nanostructures which are leading candidate for optical applications.


A multiscale stratigraphic investigation of the context of StW 573 'Little Foot' and Member 2, Sterkfontein Caves, South Africa.
The Sterkfontein Caves is currently the world's richest Australopithecus-bearing site. Included in Sterkfontein's hominin assemblage is StW 573 ('Little Foot'), a near-complete Australopithecus skeleton discovered in Member 2 in the Silberberg Grotto. Because of its importance to the fossil hominin record, the geological age of StW 573 has been the subject of significant debate. Three main hypotheses have been proposed regarding the formation and age of Member 2 and by association StW 573. The first proposes that Member 2 (as originally defined in the type section in the Silberberg Grotto) started to accumulate at around 2.58 Ma and that the unit is contained within the Silberberg Grotto. The second proposes that Member 2 started forming before 3.67 ± 0.16 Ma and that the deposit extends into the Milner Hall and close to the base of the cave system. The third proposes a 'two-stage burial scenario', in which some sediments and StW 573 represent a secondary and mixed-age accumulation reworked from a higher cave. The stratigraphic and sedimentological implications of these hypotheses are tested here through the application of a multiscale investigation of Member 2, with reference to the taphonomy of the StW 573 skeleton. The complete infilling sequence of Member 2 is described across all exposures of the deposit in the Silberberg Grotto and into the Milner Hall. Sediments are generally stratified and conformably deposited in a sequence of silty sands eroded from well-developed lateritic soils on the landscape surface. Voids, clasts and bioclasts are organized consistently across and through Member 2 conforming with the underlying deposit geometry, indicating gradual deposit accretion with no distinct collapse facies evident and only localized intra-unit postdepositional modification. The stratigraphy and sedimentology of Member 2 support a simple single-stage accumulation process of Member 2 and a primary association between the sediments of Member 2 and the StW 573 'Little Foot' skeleton.


Recipient-derived EDA fibronectin promotes cardiac allograft fibrosis.
Advances in donor matching and immunosuppressive therapies have decreased the prevalence of acute rejection of cardiac grafts; however, chronic rejection remains a significant obstacle for long-term allograft survival. While initiating elements of anti-allograft immune responses have been identified, the linkage between these factors and the ultimate development of cardiac fibrosis is not well understood. Tissue fibrosis resembles an exaggerated wound healing response, in which extracellular matrix (ECM) molecules are central. One such ECM molecule is an alternatively spliced isoform of the ubiquitous glycoprotein fibronectin (FN), termed extra domain A-containing cellular fibronectin (EDA cFN). EDA cFN is instrumental in fibrogenesis; thus, we hypothesized that it might also regulate fibrotic remodelling associated with chronic rejection. We compared the development of acute and chronic cardiac allograft rejection in EDA cFN-deficient (EDA(-/-)) and wild-type (WT) mice. While EDA(-/-) mice developed acute cardiac rejection in a manner indistinguishable from WT controls, cardiac allografts in EDA(-/-) mice were protected from fibrosis associated with chronic rejection. Decreased fibrosis was not associated with differences in cardiomyocyte hypertrophy or intra-graft expression of pro-fibrotic mediators. Further, we examined expression of EDA cFN and total FN by whole splenocytes under conditions promoting various T-helper lineages. Conditions supporting regulatory T-cell (Treg) development were characterized by greatest production of total FN and EDA cFN, though EDA cFN to total FN ratios were highest in Th1 cultures. These findings indicate that recipient-derived EDA cFN is dispensable for acute allograft rejection responses but that it promotes the development of fibrosis associated with chronic rejection. Further, conditions favouring the development of regulatory T cells, widely considered graft-protective, may drive production of ECM molecules which enhance deleterious remodelling responses. Thus, EDA cFN may be a therapeutic target for ameliorating fibrosis associated with chronic cardiac allograft rejection.


What Is Chronic Cough? Terminology.
Terminology used to define clinical cough is based on features such as duration, underlying causes, and associated characteristics such as whether the cough is "dry" or "productive." Terms such as "refractory chronic cough," "unexplained chronic cough," and "idiopathic cough" are commonly used to describe a cough that persists despite extensive investigation and therapeutic trials. The use of these terms, sometimes interchangeably, has led to a degree of confusion and with the emergence of the new clinical and mechanisitic concept associated with cough, "cough hypersensitivity syndrome," there is a need for some clarity in the nomenclature used to describe this condition.


A highly sensitive ppb-level H2S gas sensor based on fluorophenoxy-substituted phthalocyanine cobalt/rGO hybrids at room temperature.
The peripheral and non-peripheral substitution of 4-trifluoromethylphenoxy groups in the design of gas sensing phthalocyanine cobalt/reduced graphene oxide (rGO) hybrids with two different positions of the substituents was realized. Tetra-α(β)-(4-trifluoromethylphenoxy)phthalocyanine cobalt/reduced graphene oxide (3(4)-cF3poPcCo/rGO) hybrids were prepared through noncovalent interaction, and were analyzed by FT-IR, UV-vis, TGA and SEM. The gas sensing performance of the cF3poPcCo/rGO hybrid gas sensors towards ppb hydrogen sulfide (H2S) was measured at room temperature. The results show that the 4-cF3poPcCo/rGO sensor has better sensitivity, selectivity and reproducibility than the 3-cF3poPcCo/rGO sensor, as well as a perfect linear response to the concentration of H2S. For the 4-cF3poPcCo/rGO sensor, the response sensitivity to 1 ppm H2S is as high as 46.58, the response and recovery times are 600 s and 50 s for 1 ppm H2S, and the detection limit is as low as 11.6 ppb. This is mainly due to the loose and porous structure of the cF3poPcCo/rGO hybrids, the fact that graphene is an excellent conductive agent, and the fact that the electron-withdrawing capability of the trifluoromethyl group can increase the holes of rGO and PcCo. In addition, through electrochemical impedance spectroscopy (EIS) and I-V curves, and density functional theory, the influence of different positions of the substituents of cF3poPcCo/rGO on the sensing performance and the sensing mechanism for improving sensitivity were discussed and confirmed in detail.


What animals can teach us about evolution, the human genome, and human disease.
During the past 20 years, since I started as a postdoc, the world of genetics and genomics has changed dramatically. My main research goal throughout my career has been to understand human disease genetics, and I have developed comparative genomics and comparative genetics to generate resources and tools for understanding human disease. Through comparative genomics I have worked to sequence enough mammals to understand the functional potential of each base in the human genome as well as chosen vertebrates to study the evolutionary changes that have given many species their key traits. Through comparative genetics, I have developed the dog as a model for human disease, characterising the genome itself and determining a list of germ-line loci and somatic mutations causing complex diseases and cancer in the dog. Pulling all these findings and resources together opens new doors for understanding genome evolution, the genetics of complex traits and cancer in man and his best friend.


Local release of myocardial norepinephrine during acute ischemia: an experimental study in the isolated perfused rat heart.
The appearance of an early ischemia-induced local release of myocardial norepinephrine (NE) was examined in the isolated Langendorff-perfused rat heart prelabeled with [3H]NE. Either glucose or lactate was used as the perfusion substrate. Ischemia for a 60-min period was produced by global flow reduction (by 90%) or left coronary artery ligation followed by a 15-min reperfusion period. During the first 20 min of ischemia both the concentration of [3H]NE and the fraction of total 3H representing nonmetabolized [3H]NE were increased in the coronary venous effluent. This early increase in [3H]NE concentration was most pronounced in hearts with global ischemia perfused with lactate as substrate (from 19 +/- 2 to 524 +/- 76 fmol/ml/g after 20 min of ischemia). The quantity of [3H]NE released was then further increased during the 60-min period of ischemia. Reperfusion of the ischemic myocardium was associated with a marked outflow of [3H]NE and [3H]NE metabolites, primarily representing a washout from the ischemic tissue. Under the present experimental conditions the ischemia-induced release of NE was attenuated by glucose, probably owing to an ongoing glycolytic ATP formation. This effect was most pronounced during global low-flow ischemia. It is concluded that ischemia is associated with a local release of myocardial NE. In the nonworking Langendorff heart preparation, clear evidence of such a local release was already obtained after 10-20 min of ischemia.


Do apoptotic mechanisms regulate synaptic plasticity and growth-cone motility?
Signals between neurons are transduced primarily by receptors, and second messenger and kinase cascades, located in pre- and postsynaptic terminals. Such synaptic signaling pathways include those activated by neurotransmitters, cytokines, neurotrophic factors, and cell-adhesion molecules. Many of these signaling systems are also localized in the growth cones of axons and dendrites, where they control pathfinding and synaptogenesis during development. Although it has been known for decades that such signaling pathways can affect the survival of neurons, by promoting or preventing a form of programmed cell death known as apoptosis, we have discovered that apoptotic biochemical cascades can exert local actions on the functions and structural dynamics of growth cones and synapses. In this article, we provide a brief background on apoptotic biochemical cascades, and present examples of studies in this laboratory that have identified novel apoptotic and anti-apoptotic signaling mechanisms that are activated and act locally in synapses, growth cones, and dendrites to modify their structure and function. Apoptotic synaptic cascades that may play roles in neuronal plasticity include activation of caspases that can cleave certain types of ionotropic glutamate-receptor subunits and thereby modify synaptic plasticity. Caspases may also cleave cytoskeletal protein substrates in growth cones of developing neurons and may thereby regulate neurite outgrowth. Par-4 and the tumor-suppressor protein p53 are pro-apoptotic proteins that may also function in synaptic and developmental plasticity. Examples of anti-apoptotic signals that regulate the plasticity of growth cones and synapses include neurotrophic factor-activated kinase cascades, calcium-mediated actin depolymerization, and activation of the transcription factor NF-kappaB. The emerging data strongly suggest that many of the signaling mechanisms that control apoptosis are also involved in regulating the structural and functional plasticity of neuronal circuits under physiological conditions.


Regulation of transforming growth factor β1-dependent aldose reductase expression by the Nrf2 signal pathway in human mesangial cells.
Aldose reductase (AR) is a key enzyme in the alternative glucose metabolism pathway, the polyol pathway. To date, AR is known to be involved in several secondary complications of diabetes and various kidney diseases. The goal of this study was to elucidate how the Nrf2-anti-oxidant response element (ARE) signal pathway plays a role in TGFβ1's regulation of AR expression in human renal mesangial cells (HRMCs). As an in vitro model system, HRMCs were used to investigate AR mRNA by qPCR, protein by Western blot and enzymatic activity by spectrophotometric assay. The ability of TGFβ1 to induce reactive oxygen species (ROS) in cells was measured by electron-spin resonance (ESR) trapping method. Reporter assays were used to test the activity of the AR promoter region, and ChIP was employed to test the direct binding of Nrf2 with the endogenous AR promoter. Treatment of HRMCs with TGFβ1 up-regulated the expression of AR mRNA, protein, and activity level. Additionally, TGFβ1 rapidly increased cellular ROS levels, which in turn activated the Nrf2-ARE pathway. Either inhibition of ROS production or knockdown of Nrf2 in HRMCs decreased the TGFβ1-induction of AR expression. Nrf2 regulated AR luciferase activity specifically via two AREs within the AR promoter, and bound directly to the endogenous AR promoter. Furthermore, the TGFβ1-mediated expression of AR required Nrf2 and was significantly abrogated in Nrf2-/- cells. These data show the regulation of AR by TGFβ1 is induced by TGFβ1 stimulation of ROS, which activates the Nrf2-ARE pathway allowing Nrf2 to directly increase AR expression in HRMCs.


[Ossifying adrenocortical carcinoma with myelolipoma].
In a 25-year-old female in adrenocortical carcinoma with a myelolipoma and areas of ossification was removed by operation. The carcinoma did not penetrate the myeloadipose structure. The finding of an actively growing bone within the stroma of the adenocarcinoma can be explained by the local action of androgens produced by the tumour tissue.


Universal analytical scattering form factor for shell-, core-shell, or homogeneous particles with continuously variable density profile shape.
A novel analytical and continuous density distribution function with a widely variable shape is reported and used to derive an analytical scattering form factor that allows us to universally describe the scattering from particles with the radial density profile of homogeneous spheres, shells, or core-shell particles. Composed by the sum of two Fermi-Dirac distribution functions, the shape of the density profile can be altered continuously from step-like via Gaussian-like or parabolic to asymptotically hyperbolic by varying a single "shape parameter", d. Using this density profile, the scattering form factor can be calculated numerically. An analytical form factor can be derived using an approximate expression for the original Fermi-Dirac distribution function. This approximation is accurate for sufficiently small rescaled shape parameters, d/R (R being the particle radius), up to values of d/R ≈ 0.1, and thus captures step-like, Gaussian-like, and parabolic as well as asymptotically hyperbolic profile shapes. It is expected that this form factor is particularly useful in a model-dependent analysis of small-angle scattering data since the applied continuous and analytical function for the particle density profile can be compared directly with the density profile extracted from the data by model-free approaches like the generalized inverse Fourier transform method.


7-Nitroindazole impedes erythrocyte flow response to isovolemic hemodilution in the cerebral capillary circulation.
The role of nitric oxide (NO) in the mechanism of hemodilution-induced cerebral hyperemia is unclear. Based on findings in hypoxemia, the authors hypothesize that NO of neuronal origin contributes to an increase in velocity of erythrocytes in the cerebral microcirculation during anemia produced by isovolemic hemodilution. The change in erythrocyte velocity in cerebrocortical capillaries was assessed by intravital fluorescence video microscopy. A closed cranial window was implanted over the frontoparietal cortex of barbiturate-anesthetized, ventilated adult rats. Erythrocytes were labeled in vitro with fluorescein isothiocyanate and infused intravenously, and their velocity in subsurface capillaries was measured by frame-to-frame image tracking. Arterial blood was withdrawn in increments of 2 mL and replaced by serum albumin; arterial blood pressure was maintained at control level with an infusion of methoxamine. Erythrocyte velocity increased progressively, reaching 215% of baseline, as arterial hematocrit was reduced from 45% to 17%. Pretreatment of a separate group of rats with 7-nitroindazole (20 mg/kg intraperitoneally), a relatively selective inhibitor of neuronal NO synthase, abolished the increase in velocity at hematocrits greater than 20%, but the maximum velocity attained at the lowest hematocrit was similar to that in the control group. The results suggest that NO from neuronal source may contribute to the increase in capillary erythrocyte flow during moderate isovolemic hemodilution.


The Demographic Specific Abdominal Fat Composition and Distribution Trends in US Adults from 2011 to 2018.
Despite the rising awareness of abdominal adiposity associated health problems and demographic health disparities, research is lacking about abdominal fat trends using a national representative sample of US adults. Our purpose was to examine national demographic specific abdominal fat composition and distribution trends from 2011 to 2018. This trend analysis was using National Health and Nutrition Examination Survey data (n = 13,163). Visceral adipose percent (VAT%), visceral adipose tissue area (VAA) and visceral to subcutaneous adipose area ratio (VSR) were utilized in data analyses. Multiple polynomial linear regression was utilized with adjustment for confounding variables. Our findings revealed that VAT%, VAA and VSR trends were concave among all demographic groups. The VAT%, VAA and/or VSR changes were observed in most demographic groups (p < 0.05) except younger, White and Black respondents. The pattern was consistent with biennial increases up to 2014 or 2016 followed by decreases in 2017-2018. There were demographic disparities, with middle-aged respondents and Hispanics having the most evident VAT%, VSR and/or VAA changes biennially when compared to their counterparts (p < 0.05). In conclusion, abdominal fat composition and distribution increased before 2014 or 2016 but decreased afterwards with variations by age and/or race/ethnicity. Further research is needed to explore the possible causes of abdominal fat changes overtime.


Better elementary number processing in higher skill arithmetic problem solvers: evidence from the encoding step.
This paper addresses the relationship between basic numerical processes and higher level numerical abilities in normal achieving adults. In the first experiment we inferred the elementary numerical abilities of university students from the time they needed to encode numerical information involved in complex additions and subtractions. We interpreted the shorter encoding times in good arithmetic problem solvers as revealing clearer or more accessible representations of numbers. The second experiment shows that these results cannot be due to the fact that lower skilled individuals experience more maths anxiety or put more cognitive efforts into calculations than do higher skilled individuals. Moreover, the third experiment involving non-numerical information supports the hypothesis that these interindividual differences are specific to number processing. The possible causal relationships between basic and higher level numerical abilities are discussed.


Spinal ganglia reduction in the splotch-delayed mouse neural tube defect mutant.
Splotch and splotch-delayed mutants have anomalies in certain neural crest cell derivatives as well as neural tube defects. A genetic marker was used to identify mutant, heterozygote, and wild-type embryos within a litter, which enabled us to make intergenotypic comparisons. Histological studies of the lumbosacral region of day 15 and day 16 embryos indicated that the splotch-delayed mutant had similar but less severe defects in spinal ganglion development than those reported for splotch (Auerbach: Journal of Experimental Zoology 127:305-329, 1954). The ganglia were extensively reduced in size, residual, or missing in the splotch-delayed mutant, whereas in the splotch mutant, they were virtually nonexistent. Paired comparison analyses showed that all mutant embryos had a significant reduction in their volume of lumbosacral spinal ganglia when compared to their heterozygous and/or wild-type littermates. Also, some heterozygotes were found to have spinal ganglia volumes that were significantly reduced when compared to wild-type embryos. The volume of spinal ganglia was not related to the severity of the neural tube defect. In fact, three mutant embryos, which did not exhibit a neural tube defect, had spinal ganglia volumes comparable to or less than those mutants with open neural tube lesions or curly tails. This shows that the formation of abnormal neural crest cell derivatives is not a result of the neural tube closure defect. We hypothesize that the two anomalies observed in these mutants have a common etiological basis.


The causal effect of life course adiposity on periodontitis: A Mendelian randomization study.
To establish whether life course adiposity, including birth weight (BW), childhood and adulthood body mass index (BMI), waist-hip ratio (WHR), and body fat percentage (BF%), has a causal influence on periodontitis. We used single-nucleotide polymorphisms with significant associations with life course adiposity as instrumental variables. We examined their association with periodontitis risk in a genome-wide association study involving periodontitis cases (n = 17,353) and healthy controls (n = 28,210) using a two-sample Mendelian randomization (MR) strategy. The association of life course adiposity with periodontitis risk was estimated with inverse-variance weighting with random effects. We performed sensitivity analyses using MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO), weighted median, and MR-Egger methods. We calculated the odds ratios (ORs) for one standard deviation (SD) increase per risk factor to estimate the effect on the risk of periodontitis. After correction for multiple testing, there was an association between each SD increase in gene-predicted adulthood BMI with a higher periodontitis risk (OR = 1.15, 95% confidence interval [CI]: 1.06-1.23, p = 3.1 × 10-4), with a similar influence for BF% on periodontitis risk (OR = 1.29, 95% CI: 1.12-1.49, p = 3.3 × 10-4). No causal association was detected for gene-predicted BW, childhood BMI, or WHR with periodontitis risk. We present new proof supporting a causal function of greater adiposity, especially high BMI and BF%, being associated with higher periodontitis risk. We recommend that future studies focus on periodontitis from a life course perspective.


Chronic inflammatory cardiomyopathy of interferon γ-overexpressing transgenic mice is mediated by tumor necrosis factor-α.
We recently described a model of inflammatory cardiomyopathy in interferon (IFN)-γ overexpressing transgenic mice stably circulating IFN-γ in the serum referred to as SAP--IFN-γ mice. SAP-IFN-γ transgenic mice show cardiac infiltration by mononuclear leukocytes, culminating in dilated cardiomyopathy characterized by an increase of left ventricular end diastolic diameter and reduction of fractional shortening. We hypothesized that the pathological mechanism underlying SAP-IFN-γ cardiomyopathy might be mediated by (auto)immune processes or tumor necrosis factor (TNF)-α synthesis from IFN-γ-activated macrophages. To verify these hypotheses, we crossed SAP-IFN-γ transgenic mice with immunodeficient Rag1(-/-) or TNF-α(-/-) knockout mice and analyzed the cardiac phenotype of the resulting double-mutant offspring. Immunodeficient Rag1(-/-) SAP-IFN-γ mice had a decreased impaired life span and intensive cardiac inflammatory reactions, showing that the cardiotoxic IFN-γ effect operative in SAP-IFN-γ mice was not mediated by an adaptive immune mechanism. SAP-IFN-γ TNF-α(-/-) hearts showed virtually no histopathological alterations, a significant reduction of cardiac infiltration by CD11c(+) dendritic cells and F4/80(+) macrophages, almost complete normalization of cardiac troponin T levels in serum and of left ventricular end diastolic diameter and fractional shortening, and a dramatic increase of life span, compared with SAP-IFN-γ transgenic controls. Thus, myocarditis and cardiomyopathy developing in IFN-γ-overexpressing transgenic mice is, to a significant degree, mediated by TNF-α. TNF-α-mediated cardiotoxicity in SAP-IFN-γ transgenic mice is independent of changes of apoptosis.


Analysis of coagulation and fibrinolysis during intravenous infusion of recombinant human tissue-type plasminogen activator in patients with acute myocardial infarction.
Coagulation and fibrinolysis were studied in patients with acute myocardial infarction during intravenous infusion of recombinant human tissue-type plasminogen activator (rt-PA) (0.75 mg/kg over 90 min, n = 101), streptokinase (1,500,000 IU over 60 min, n = 61), or placebo (n = 40). In the rt-PA group, the plasma level of rt-PA antigen was 1.2 +/- 0.6 micrograms/ml (mean +/- SD) and the euglobulin fibrinolytic activity (EFA) was 910 +/- 735 IU t-PA/ml. In the streptokinase group, the EFA was equivalent to 430 +/- 435 IU t-PA/ml. At the end of the infusion, the plasma fibrinogen level measured with a coagulation rate assay was decreased to 57 +/- 33% of the preinfusion value in the rt-PA group, to 7 +/- 10% in the streptokinase group, and remained unchanged in the placebo group. Fibrinogen-fibrin degradation products increased to 0.75 +/- 0.54 mg/ml in the streptokinase group but to only 0.10 +/- 0.13 mg/ml in the rt-PA group. The plasma levels of alpha 2-antiplasmin, plasminogen, and factor V decreased to between 30% and 45% in the rt-PA group but significantly more in the streptokinase group (to between 15% and 25%). Thus rt-PA induced much less systemic fibrinolytic activation than streptokinase. In the patients who received rt-PA, a weak correlation (r = .21, n = 89, .1 greater than p greater than .05) was found between the extent of fibrinogen breakdown at 90 min and the plasma rt-PA concentration.(ABSTRACT TRUNCATED AT 250 WORDS)


[An unusual course of thoracic actinomycosis].
A 56-year-old farmer who had been suffering from exogenous allergic alveolitis developed, after a long prodromal period of illness, a granulocyte-rich pericardial effusion and bilateral pleural effusions in which Actinomyces aggregates were identified. Despite intensive treatment with clindamycin, erythromycin and tetracycline (he was allergic to penicillin) he died in septic shock.


Double-stranded RNA-mediated interference with plant virus infection.
Double-stranded RNA (dsRNA) has been shown to play a key role as an inducer of different interference phenomena occurring in both the plant and animal kingdoms. Here, we show that dsRNA derived from viral sequences can interfere with virus infection in a sequence-specific manner by directly delivering dsRNA to leaf cells either by mechanical inoculation or via an Agrobacterium-mediated transient-expression assay. We have successfully interfered with the infection of plants by three viruses belonging to the tobamovirus, potyvirus, and alfamovirus groups, demonstrating the reliability of the approach. We suggest that the effect mediated by dsRNA in plant virus infection resembles the analogous phenomenon of RNA interference observed in animals. The interference observed is sequence specific, is dose dependent, and is triggered by dsRNA but not single-stranded RNA. Our results support the view that a dsRNA intermediate in virus replication acts as efficient initiator of posttranscriptional gene silencing (PTGS) in natural virus infections, triggering the initiation step of PTGS that targets viral RNA for degradation.


[Forensic psychiatry evaluation in determining free will and legal competence].
Freedom of will is the prerequisite for legal capacity. In adults, it can be repealed only by a psychiatric illness. On the part of the jurists a restrictive handling is stipulated. A theory of will and action accepted by jurisprudence and psychology/psychiatry in like manner is missing. From the viewpoint of the psychiatric expert, the diagnosis presents a frame of orienting lines, in which the analysis of the psychopathological findings yields the basis of judgement. The proceeding is described for the particular groups of diseases. Thereby the specific problems are discussed and proposals to solve them are drawn up. Further, the prerequisites for the capacity to give consent to methods of medical treatment are commented.


Thermal emission from haze and clouds.
The photons thermally emitted by the atmospheric molecules and aerosols as well as those emitted by the planetary surface are followed by a Monte Carlo technique through subsequent collisions with the aerosols and planetary surface. Anisotropic single scattering functions typical of hazes or of nimbostratus clouds are used. The angular variation of the radiation at both the top and bottom of the atmosphere are studied as a function of the single scattering albedo, size distribution of aerosols, optical thickness of the atmosphere, albedo and temperature of planetary surface, and the temperature distribution in the atmosphere.


Treatment of exophthalmos.
Current procedures for Graves' exophthalmos fail to achieve complete correction. The standard orbital decompressions were therefore modified to maximize the degree of volumetric increase behind the axis of the globe. In 15 orbits, the preoperative exophthalmos averaged 9.5 mm, whereas the postoperative exophthalmos was 4.1 mm. Postoperative CT study demonstrated that the remaining posterior orbital wall, combined with the persistently increased intraocular muscle volume, blocked retrodisplacement of the globe, despite adequate total volumetric increase. The increased muscle volume varied from 2 to 5 cc. Despite this residual exophthalmos, the modified four-wall expansion provides excellent aesthetic results with visual improvement and resolution of chemosis and exposure keratitis.


Screening for vision-threatening diabetic retinopathy in South India: comparing portable non-mydriatic and standard fundus cameras and clinical exam.
PurposeTo evaluate the sensitivity and specificity of a portable non-mydriatic fundus camera to diagnose vision-threatening diabetic retinopathy (VTDR).Patients and methodsA prospective, single-site, comparative instrument validation study was undertaken at the Aravind Eye Care System. Overall, 155 subjects with and without diabetes were recruited. Images from 275 eyes were obtained with the (1) non-mydriatic Smartscope, (2) mydriatic Smartscope, and (3) mydriatic table-top camera of the macular, nasal, and superotemporal fields. A retina specialist performed a dilated fundus examination (DFE), (reference standard). Two masked retina specialists graded the images. Sensitivity and specificity to detect VTDR with the undilated Smartscope was calculated compared to DFE.ResultsGraders 1 and 2 had a sensitivity of 93% (95% confidence interval (CI): 87-97%) and 88% (95% CI: 81-93%) and a specificity of 84% (95% CI: 77-89%) and 90% (95% CI: 84-94%), respectively, in diagnosing VTDR with the undilated Smartscope compared to DFE. Compared with the dilated Topcon images, graders 1 and 2 had sensitivity of 88% (95% CI: 81-93%) and 82% (95% CI: 73-88%) and specificity of 99% (95% CI: 96-100%) and 99% (95% CI: 95-100%).ConclusionsRemote graders had high sensitivity and specificity in diagnosing VTDR with undilated Smartscope images, suggesting utility where portability is a necessity.


The post-antifungal effect (PAFE) of amphotericin B, nystatin, ketoconazole and 5-fluorocytosine and its impact on the colonization traits of Candida glabrata.
The post-antifungal effect (PAFE) has been shown to affect Candida pathogenicity, but there is little information on either PAFE or its association with the colonization traits of Candida glabrata. The objective of this study was to determine, in vitro, the PAFE on 14 C. glabrata isolates following exposure to amphotericin B (AMB), nystatin (NYS), ketoconazole (KETO) and 5-fluorocytosine (5FC). In addition, we evaluated the impact of PAFE on yeast adherence to buccal epithelial cells (BEC), cell-surface-hydrophobicity (CSH) and biofilm growth (BG) on denture acrylic surfaces. PAFE was induced following a 1-h exposure of yeasts to (x1-x4MIC) of AMB, NYS, KETO and 5FC in RPMI medium and, measured using automated turbidometry. The BEC adhesion, CSH and BG assays were performed by the methods of Kimura & Pearsall, Sweet et al., and Jin et al., respectively. Significant differences in PAFE (P < 0.001) were observed after exposure to AMB and NYS, but not KETO and 5FC. Following exposure to AMB, NYS, KETO and 5FC, significant inter-strain differences (P < 0.001) were observed in percentage terms in adhesion (39.0%, 43.48%, 38.28%, 35.07%) and biofilm growth (42.86%, 39.86%, 42.81%, 36.38%), respectively. Short exposure of C. glabrata to sub-cidal concentrations of antifungals modulates yeast growth and also affects some of their colonization traits.


Molecular Mechanisms, Biomarkers and Emerging Therapies for Chemotherapy Resistant TNBC.
Triple-negative breast cancer (TNBC) is associated with high recurrence rates, high incidence of distant metastases, and poor overall survival (OS). Taxane and anthracycline-containing chemotherapy (CT) is currently the main systemic treatment option for TNBC, while platinum-based chemotherapy showed promising results in the neoadjuvant and metastatic settings. An early arising of intrinsic or acquired CT resistance is common and represents the main hurdle for successful TNBC treatment. Numerous mechanisms were uncovered that can lead to the development of chemoresistance. These include cancer stem cells (CSCs) induction after neoadjuvant chemotherapy (NACT), ATP-binding cassette (ABC) transporters, hypoxia and avoidance of apoptosis, single factors such as tyrosine kinase receptors (EGFR, IGFR1), a disintegrin and metalloproteinase 10 (ADAM10), and a few pathological molecular pathways. Some biomarkers capable of predicting resistance to specific chemotherapeutic agents were identified and are expected to be validated in future studies for a more accurate selection of drugs to be employed and for a more tailored approach, both in neoadjuvant and advanced settings. Recently, based on specific biomarkers, some therapies were tailored to TNBC subsets and became available in clinical practice: olaparib and talazoparib for BRCA1/2 germline mutation carriers larotrectinib and entrectinib for neurotrophic tropomyosin receptor kinase (NTRK) gene fusion carriers, and anti-trophoblast cell surface antigen 2 (Trop2) antibody drug conjugate therapy for heavily pretreated metastatic TNBC (mTNBC). Further therapies targeting some pathologic molecular pathways, apoptosis, miRNAS, epidermal growth factor receptor (EGFR), insulin growth factor 1 receptor (IGF-1R), and androgen receptor (AR) are under investigation. Among them, phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) and EGFR inhibitors as well as antiandrogens showed promising results and are under evaluation in Phase II/III clinical trials. Emerging therapies allow to select specific antiblastics that alone or by integrating the conventional therapeutic approach may overcome/hinder chemoresistance.


Hepatic encephalopathy EEG and octopamine.
In a group of 30 patients with and without hepatic encephalopathy octopamine values were determined and EEG recorded. The data reported show no relationship between octopamine values and presence or seriousness of hepatic encephalopathy but showed a clear correlation between hepatic encophalopathy and electroencephologram disturbance.


Prognostic molecular biomarkers in chordomas: A systematic review and identification of clinically usable biomarker panels.
Despite the improvements in management and treatment of chordomas over time, the risk of disease recurrence remains high. Consequently, there is a push to develop effective systemic therapeutics for newly diagnosed and recurrent disease. In order to tailor treatment for individual chordoma patients and develop effective surveillance strategies, suitable clinical biomarkers need to be identified. The objective of this study was to systematically review all prognostic biomarkers for chordomas reported to date in order to classify them according to localization, study design and statistical analysis. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically reviewed published studies reporting biomarkers that correlated with clinical outcomes. We included time-to-event studies that evaluated biomarkers in skull base or spine chordomas. To be included in our review, the study must have analyzed the outcomes with univariate and/or multivariate methods (log-rank test or a Cox-regression model). We included 68 studies, of which only 5 were prospective studies. Overall, 103 biomarkers were analyzed in 3183 patients. According to FDA classification, 85 were molecular biomarkers (82.5%) mainly located in nucleus and cytoplasm (48% and 27%, respectively). Thirty-four studies analyzed biomarkers with Cox-regression model. Within these studies, 32 biomarkers (31%) and 22 biomarkers (21%) were independent prognostic factors for PFS and OS, respectively. Our analysis identified a list of 13 biomarkers correlating with tumor control rates and survival. The future point will be gathering all these results to guide the clinical validation for a chordoma biomarker panel. Our identified biomarkers have strengths and weaknesses according to FDA's guidelines, some are affordable, have a low-invasive collection method and can be easily measured in any health care setting (RDW and D-dimer), but others molecular biomarkers need specialized assay techniques (microRNAs, PD-1 pathway markers, CDKs and somatic chromosome deletions were more chordoma-specific). A focused list of biomarkers that correlate with local recurrence, metastatic spread and survival might be a cornerstone to determine the need of adjuvant therapies.


Accelerated graft dysfunction in heart transplant patients with persistent atrioventricular conduction block.
Bradyarrhythmia following heart transplantation is common-∼7.5-24% of patients require permanent pacemaker (PPM) implantation. While overall mortality is similar to their non-paced counterparts, the effects of chronic right ventricular pacing (CRVP) in heart transplant patients have not been studied. We aim to examine the effects of CRVP on heart failure and mortality in heart transplant patients. Records of heart transplant recipients requiring PPM at St Vincent's Hospital, Sydney, Australia between January 1990 and January 2015 were examined. Patient's without a right ventricular (RV) pacing lead or a follow-up time of <1 year were excluded. Patients with pre-existing abnormal left ventricular function (<50%) were analysed separately. Patients were grouped by pacing dependence (100% pacing dependent vs. non-pacing dependent). The primary endpoint was clinical or echocardiographic heart failure (<35%) in the first 5 years post-PPM. Thirty-three of 709 heart transplant recipients were studied. Two patients had complete RV pacing dependence, and the remaining 31 patients had varying degrees of pacing requirement, with an underlying ventricular escape rhythm. The primary endpoint occurred significantly more in the pacing-dependent group; 2 (100%) compared with 2 (6%) of the non pacing dependent group (P < 0.0001 by log-rank analysis, HR = 24.58). Non-pacing-dependent patients had reversible causes for heart failure, unrelated to pacing. In comparison, there was no other cause of heart failure in the pacing-dependent group. Permanent atrioventricular block is rare in the heart transplant population. We have demonstrated CRVP as a potential cause of accelerated graft failure in pacing-dependent heart transplant patients.


Intelligent packaging films incorporated with anthocyanins-loaded ovalbumin-carboxymethyl cellulose nanocomplexes for food freshness monitoring.
An intelligent colorimetric film was prepared to monitor mushrooms freshness by incorporating anthocyanin-loaded ovalbumin-carboxymethyl cellulose nanocomplexes (OVA-CMC-ACNs) into corn starch/polyvinyl alcohol matrix. The results showed that ACNs could be loaded into OVA-CMC nanocomplexes with larger particle size and more uniform size distribution. The structure, physical properties, colorimetric response and practical application of films were studied. Compared with SP/ACNs film incorporation of free anthocyanins, SP/OVA-CMC-ACNs film had denser structure, higher mechanical and water barrier properties, and better thermal stability, which were related to the hydrogen bond among film components by FT-IR. The SP/OVA-CMC-ACNs film showed obvious colorimetric response in CO2 gas and pH buffer. The successful applications of intelligent film for the freshness monitoring of mushrooms. The intelligent film could monitor the freshness of mushrooms during the storage by visual color change from purple to pink. These results indicated that prepared SP/OVA-CMC-ACNs film have great application potential in intelligent food packaging.


Revisit of Broden's view for intraarticular calcaneal fracture.
This study was performed to investigate the relationship between coronal computed tomography (CT) and Broden's view in terms of location of the fracture line and fracture pattern. Forty-five feet of 45 patients with intraarticular calcaneal fractures were evaluated. The mean age of the patients was 46.3 years (standard deviation, 18.1; range, 15 to 80 years), and there were 34 men and 11 women. The Broden's views were acquired using the ray sum projection, reviewed, and correlated with the coronal CT image to determine the location of the fracture on the posterior facet and fracture pattern described by the Sanders classification. The quantified location of the fracture line was defined as the distance between the medial margin of posterior facet and the fracture line divided by the whole length of the posterior facet, which was expressed as a percentage. The fracture line on the Broden's view was positioned at 22.3% (standard deviation, 29.6) laterally compared to that on coronal CT (p < 0.01). Although all cases showed posterior facet involvement on the CT scan, the fracture line was positioned lateral to the posterior facet in 6 cases (13.3%) in the Broden's view. The coronal CT and Broden's view showed a low level of agreement in the fracture pattern according to the Sanders classification, with kappa values of 0.23. Surgeons should consider that the fracture line on the Broden's view shows positioning laterally compared to coronal CT and they should consider that the fracture line at the lateral to posterior facet on the Broden's view might be an intraarticular fracture line. There are some limitations when applying the Sanders classification with the Broden's view.


Coupling machine learning with signal process techniques and particle swarm optimization for forecasting flood routing calculations in the Eastern Black Sea Basin, Türkiye.
With the effect of global warming, the frequency of floods, one of the most important natural disasters, increases, and this increases the damage it causes to people and the environment. Flood routing models play an important role in predicting floods so that all necessary precautions are taken before floods reach the region, loss of life and property in the region is prevented, and agricultural lands are protected. This research aims to compare the performance of hybrid machine learning models such as least-squares support vector machine technique hybridized with particle swarm optimization, empirical mode decomposition, variational mode decomposition, and discrete wavelet transform processes for flood routing estimation models in Ordu, Eastern Black Sea Basin, Türkiye. In addition, it is aimed to examine the effect of data division in flood forecasting. Accordingly, 70%, 80%, and 90% of the data were used for training, respectively. For this purpose, the flood data of 2009 and 2013 in Ordu were used. The performance of the established models was evaluated with the help of statistical indicators such as mean bias error, mean absolute percentage error, determination coefficient, Nash-Sutcliffe efficiency, Taylor Diagrams, and boxplot. As a result of the study, the particle swarm optimization least-squares support vector machine technique was chosen as the most successful model in predicting flood routing results. In addition, the optimum data partition ratio was found to be Train:70:Test:30 in the flood routing calculation. The findings are essential regarding flood management and taking necessary precautions before the flood occurs.


Estimation of humoral activity of Eleutherococcus senticosus.
The aim of the present work was an estimation of the influence of two plant pharmaceutical preparations containing an extract from the root of Eleutherococcus senticosus: Argoeleuter tablets and Immuplant tablets, on the humoral response of immunological system. Experiments were performed with female Balb/c mice six weeks old. In order to reveal the influence of taking preparations, containing an extract from Eleutherococcus senticosus on some elements of the immunological system, three ways of their administration have been compared: before illness, during illness and a combination of both. The obtained results allow formulating the following conclusions: - the pharmaceutical preparations, containing the extract from Eleutherococcus senticosus administered orally, influence on the increase of the level of immunoglobulins comprised in the mice's blood serum, - the pharmaceutical preparations act with different power, not fully dependent on the content of marker of the active substance - eleutheroside E, - dosage of the preparations containing the extract from Eleutherococcus senticosus should not be established basing only on the extract content, - best curative results, measured as the stimulation of humoral response of the organism were obtained when a given preparation was administered therapeutically, even though the combined administration - prophylactically with prolonged administration during illness also is correct.


Shipment of insects and related arthropods into and out of India for research or commercial purposes.
This paper provides a concise summary of the guidelines and regulations that govern the shipment of insects and related arthropods into and out of India. It discusses the Plant Quarantine (Regulation of Import into India) Order, 2003, which regulates the import of agents for biological control, and the Biological Diversity Act, 2002, and associated Biological Diversity Rules, 2004, which guide the transfer of insects and related arthropods for identification, taxonomic research, and commercial purposes. Insect trade for some food and feed purposes is also mentioned. Finally, some implications, conclusions and recommendations are presented.


Glioblastoma-secreted soluble CD44 activates tau pathology in the brain.
During aggressive tumor growth and migration, glioblastoma cells secrete diverse molecules and adhesion proteins to the extracellular matrix. Yet, the biochemical effects of the glioblastoma secretome in the brain remain largely unknown. Here we show that soluble CD44 secreted from glioblastoma cells induces neuronal degeneration through the activation of tau pathology in the brain. Glioblastoma-xenograft tissues showed a number of degenerating neurons bearing highly phosphorylated tau. Through a series of secretome-analyses, we identified that soluble CD44 was the responsible protein inducing tau phosphorylation and aggregation (EC50 = 19.1 ng/mL). The treatment of sCD44 to primary hippocampal neurons-induced tau hyperphosphorylation, leading to neuronal degeneration. Also, the injection of sCD44 into the brains of tau transgenic mice induced tau hyper-phosphorylation in hippocampal neurons. Altogether, our data suggest a neurodegenerative role of sCD44 in promoting tau pathology and serving as a molecular link between glioblastoma and neurodegeneration.


Assessing driving-relevant attentional impairment after a multiday drinking session: A two-phase pilot study.
The possibility of residual impairment of cognitive performance after multiday drinking sessions is particularly important given the potential for the deleterious effects of fatigue and hangover. This pilot study aimed to devise a methodology to compare sober performance on driving-relevant attentional tasks at the end of a 4-day music festival with performance at varying levels of the breath-alcohol curve. Fifty-two participants completed selective and sustained attention tasks at a breath alcohol concentration (BrAC) of 0.00%, 0.05%, and 0.08% following acute dosing in a controlled laboratory setting. A subset of participants (n = 13) were then tested at the conclusion of a 4-day music festival at 0.00% BrAC, with task performance compared with laboratory results. During the laboratory phase, sustained attention was poorer at the 0.05% ascending timepoint only (compared to 0.00% BrAC). During the festival phase, participants made a greater number of errors on the selective attention task predeparture than at 0.00% and 0.05% BrAC in the laboratory. Sustained attention performance was poorer while intoxicated in the laboratory. Our findings suggest that the absence of blood alcohol acutely may not be indicative of unimpaired cognitive performance and that other factors related to multiday drinking may produce driving-related attentional deficits. The findings reinforce the need to measure attentional performance in real-world drinking contexts despite the methodological complexities of doing so. A larger study is warranted to replicate the findings and should include attentional measures that either are more sensitive to the effects of acute alcohol intoxication than those in our study or are based on a driving simulator.


Spinal epidural abscess: prognostic factors and comparison of different surgical treatment strategies.
Spinal epidural abscess (SEA) is a rare but potentially devastating disease requiring immediate surgical intervention and appropriate antibiotic treatment. The standard approach to decompress SEA is laminectomy. No report covers comprehensively the indications for the less invasive interlaminar approach, the usefulness of intra-operative ultrasonography and the suspected benefit of inserting a suction-irrigation drainage. A retrospective evaluation of the medical and radiological data was undertaken in 27 consecutive patients with SEA operated on during a period of 10 years by a dorsal approach. Factors influencing outcome were evaluated with special regard to different surgical strategies concerning the invasiveness of the operative approach, the use of intra-operative ultrasound and the use of different drainage systems. Outcome was mainly determined by the pre-operative neurological condition and the localization of the abscess. Recurrence rate was dependent on the longitudinal extent of the mass and the intra-operative finding of granulation tissue, but not on the administration of a postoperative suction-irrigation drainage. An interlaminar approach was equally matched to a decompression by laminectomy in lumbar SEA concerning the incidence of residual/recurrent abscess formation. In concomitant spondylodiscitis, laminectomy bore the risk of the formation of a postoperative kyphotic deformity. The use of intra-operative ultrasound allowed the visualization of hidden inflammatory masses and, thus, reduced the rate of residual abscess formation. An interlaminar approach should be considered instead of laminectomy in lumbar SEA and in impending anterior column instability due to spondylitis. Intra-operative ultrasound is a beneficial aid for the determination of the extent of decompression during surgery and is practicable even through a narrow interlaminar bony window. The insertion of postoperative suction-irrigation drainage had no beneficial effect on outcome but bore the risk of epidural fluid congestion.


Laser power stabilization for second-generation gravitational wave detectors.
We present results on the power stabilization of a Nd:YAG laser in the frequency band from 1 Hz to 100 kHz. High-power, low-noise photodetectors are used in a dc-coupled control loop to achieve relative power fluctuations down to 5 x 10(-9) Hz(-1/2) at 10 Hz and 3.5 x 10(-9) Hz(-1/2) up to several kHz, which is very close to the shot-noise limit for 80 mA of detected photocurrent on each detector. We investigated and eliminated several noise sources such as ground loops and beam pointing. The achieved stability level is close to the requirements for the Advanced LIGO gravitational wave detector.


Extracting phylogenetic information from whole-genome sequencing projects: the lactic acid bacteria as a test case.
The availability of an ever increasing number of complete genome sequences of diverse prokaryotic taxa has led to the introduction of novel approaches to infer phylogenetic relationships among bacteria. In the present study the sequences of the 16S rRNA gene and nine housekeeping genes were compared with the fraction of shared putative orthologous protein-encoding genes, conservation of gene order, dinucleotide relative abundance and codon usage among 11 genomes of species belonging to the lactic acid bacteria. In general there is a good correlation between the results obtained with various approaches, although it is clear that there is a stronger phylogenetic signal in some data sets than in others, and that different parameters have different taxonomic resolutions. It appears that trees based on different kinds of information derived from whole-genome sequencing projects do not provide much additional information about the phylogenetic relationships among bacterial taxa compared to more traditional alignment-based methods. Nevertheless, it is expected that the study of these novel forms of information will have its value in taxonomy, to determine which genes are shared, when genes or sets of genes were lost in evolutionary history, to detect the presence of horizontally transferred genes and/or confirm or enhance the phylogenetic signal derived from traditional methods. Although these conclusions are based on a relatively small data set, they are largely in agreement with other studies and it is anticipated that similar trends will be observed when comparing other genomes.