Modification and optimization of the united-residue (UNRES) potential energy function for canonical simulations. I. Temperature dependence of the effective energy function and tests of the optimization method with single training proteins.
We report the modification and parametrization of the united-residue (UNRES) force field for energy-based protein structure prediction and protein folding simulations. We tested the approach on three training proteins separately: 1E0L (beta), 1GAB (alpha), and 1E0G (alpha + beta). Heretofore, the UNRES force field had been designed and parametrized to locate native-like structures of proteins as global minima of their effective potential energy surfaces, which largely neglected the conformational entropy because decoys composed of only lowest-energy conformations were used to optimize the force field. Recently, we developed a mesoscopic dynamics procedure for UNRES and applied it with success to simulate protein folding pathways. However, the force field turned out to be largely biased toward -helical structures in canonical simulations because the conformational entropy had been neglected in the parametrization. We applied the hierarchical optimization method, developed in our earlier work, to optimize the force field; in this method, the conformational space of a training protein is divided into levels, each corresponding to a certain degree of native-likeness. The levels are ordered according to increasing native-likeness; level 0 corresponds to structures with no native-like elements, and the highest level corresponds to the fully native-like structures. The aim of optimization is to achieve the order of the free energies of levels, decreasing as their native-likeness increases. The procedure is iterative, and decoys of the training protein(s) generated with the energy function parameters of the preceding iteration are used to optimize the force field in a current iteration. We applied the multiplexing replica-exchange molecular dynamics (MREMD) method, recently implemented in UNRES, to generate decoys; with this modification, conformational entropy is taken into account. Moreover, we optimized the free-energy gaps between levels at temperatures corresponding to a predominance of folded or unfolded structures, as well as to structures at the putative folding-transition temperature, changing the sign of the gaps at the transition temperature. This enabled us to obtain force fields characterized by a single peak in the heat capacity at the transition temperature. Furthermore, we introduced temperature dependence to the UNRES force field; this is consistent with the fact that it is a free-energy and not a potential energy function. beta


Two 7 alpha-hydroxylase enzymes in bile acid biosynthesis.
The addition of a 7-hydroxyl group is an early and often rate-limiting step in the synthesis of bile acids. This reaction is catalysed by two cytochrome P450 enzymes known as cholesterol 7 alpha-hydroxylase and oxysterol 7 alpha-hydroxylase. cDNAs encoding these proteins have been isolated and used to define two evolutionarily conserved pathways that produce 7 alpha-hydroxylated bile acids.


What are the determinants for individuals to undergo cardiovascular disease health checks? A cross sectional survey.
There is a need to improve public's participation in health checks for early identification of individuals at high risk of CVD for prevention. The objective of this study is to identify significant determinants associated with individuals' intention to undergo CVD health checks. These determinants could be used to develop effective strategies to improve CVD health check participation. This was a cross sectional survey using mall intercept interviews. It was carried out in a hypermarket surrounded by housing estates with a population of varying socioeconomic backgrounds. Inclusion criteria were Malaysian nationality and age 30 years and older. The validated CVD health check questionnaire was used to assess participants' intention and the determinants that influenced their intention to undergo CVD health checks. A total of 413 participants were recruited. The median age of the participants was 45 years (IQR 17 years) and 60% of them were female. Participants indicated they were likely (45.0%) or very likely (38.7%) to undergo CVD health checks while 16.2% were not sure, unlikely or very unlikely to undergo health checks. Using ordinal regression analysis, perception of benefits, drawbacks of CVD health checks, perception of external barriers and readiness to handle outcomes following CVD health checks were the significant determinants of individuals' intention to undergo CVD health checks. To improve individuals' participation in CVD health checks, we need to develop strategies to address their perception of benefits and drawbacks of CVD health checks, the perceived external barriers and their readiness to handle outcomes following CVD health checks.


Notch-dependent epithelial fold determines boundary formation between developmental fields in the Drosophila antenna.
Compartment boundary formation plays an important role in development by separating adjacent developmental fields. Drosophila imaginal discs have proven valuable for studying the mechanisms of boundary formation. We studied the boundary separating the proximal A1 segment and the distal segments, defined respectively by Lim1 and Dll expression in the eye-antenna disc. Sharp segregation of the Lim1 and Dll expression domains precedes activation of Notch at the Dll/Lim1 interface. By repressing bantam miRNA and elevating the actin regulator Enable, Notch signaling then induces actomyosin-dependent apical constriction and epithelial fold. Disruption of Notch signaling or the actomyosin network reduces apical constriction and epithelial fold, so that Dll and Lim1 cells become intermingled. Our results demonstrate a new mechanism of boundary formation by actomyosin-dependent tissue folding, which provides a physical barrier to prevent mixing of cells from adjacent developmental fields.


Relationship between hyperglycemia, antioxidant capacity and some enzymatic and non-enzymatic antioxidants in African patients with type 2 diabetes.
Studies demonstrate that free radicals are involved in the pathogenesis of diabetic complications. The aim of this study was to determine the implication of total antioxidant capacity (TAC) and some enzymatic and non-enzymatic antioxidants as suitable biomarkers of diabetic complications risk factors. A total of 90 patients (70 patients with or without diabetic complications +20 normal healthy) were examined by evaluating the level of lipid peroxidation, nitrogen monoxide (NO), fasting blood glucose, glycated haemoglobin (HbA1c), enzymatic and non-enzymatic antioxidants using standard spectrophotometric methods. The fasting blood glucose and HbA1c levels were respectively 2.05 and 2.32 times higher in the group of patients with diabetes and complications (DPWC) compared to those of healthy persons. A statistically higher level of malondialdehyde (MDA), NO and TAC was observed in a group of patients with diabetes and complications compared to those without complications (DPNC). A significant positive correlation was found between catalase (CAT) and fasting blood glucose while a significant and negative correlation was noted between reduced glutathione (GSH) and fasting blood glucose. Also was noted a significant relationship between HbA1c and other markers of oxidative stress. The results suggest that the plasma levels of CAT, TAC and reduced glutathione could give information on the risk of developing complications of diabetes, considering that the modification of these biomarkers levels were associated with oxidative stress.


Omics-based identification of the combined effects of idiosyncratic drugs and inflammatory cytokines on the development of drug-induced liver injury.
The mechanisms of idiosyncratic drug-induced hepatotoxicity remain largely unclear. It has demonstrated that the drug idiosyncrasy is potentiated in the context of inflammation and intracellular ceramides may play a role in this process. To study the mechanisms, HepG2 cells were co-treated with high and low doses of three idiosyncratic (I) and three non-idiosyncratic (N) compounds, with (I+ and N+) or without (I- and N-) a cytokine mix. Microarray, lipidomics and flow cytometry were performed to investigate the genome-wide expression patterns, the intracellular ceramide levels and the induction of apoptosis. We found that all I+ treatments significantly influenced the immune response- and response to stimulus-associated gene ontology (GO) terms, but the induction of apoptotic pathways, which was confirmed by flow cytometry, only appeared to be induced after the high-dose treatment. The ceramide signaling-, ER stress-, NF-kB activation- and mitochondrial activity-related pathways were biologically involved in apoptosis induced by the high-dose I+. Additionally, genes participating in ceramide metabolism were significantly altered resulting in a measurable increase in ceramide levels. The increases in ceramide concentrations may induce ER stress and activate the JNK pathway by affecting the expression of the related genes, and eventually trigger the mitochondria-independent apoptosis in hepatocytes. Overall, our study provides a potential mechanism to explain the role of inflammation in idiosyncratic drug reactions.


Vaccination Against Hepatitis A for Hemophilic Patients: Is It Necessary?
Hemophilic patients require long-life intravenous infusion of factor concentrates to treat bleedings. This could increase the risk of transmission of blood-borne infections like hepatitis C. The current study was aimed at investigating the immunity status against hepatitis A in hemophilic patients in south Khorasan and evaluating the necessity of hepatitis A vaccination for this population. A cross-sectional descriptive study was conducted between 2014 and 2015 on all hemophilic patients of south Khorasan province, Iran (n = 108) for anti-HAV total, anti- HCV, HBs-Ag, anti-HIV, and anti-HTLV-I /II. Note that no one had already received a hepatitis A vaccine. As our results show, 77.8% of the participants (59% under 20 and 88.4% above 20 years old) were seropositive for anti-HAV total; 20.4% and 2.8% (three patients) of the cases were anti-HCV positive and anti-HTLV-1 positive, respectively, while none of the subjects were HBS-Ag or HIV-Ab positive. Seventeen of the patients (15.75%) showed a co-infection of HAV with HCV, and five HCV-infected patients (22.73%) had no immunity against hepatitis A. There was a significant relationship between age, rural life, and anti-HAV positive state in our patients (P < 0.001). No significant relationship between positive anti-HAV status and sex (P = 0.16), severity of hemophilia (P = 0.23), and infection with HIV, HCV, HTLV-1, and hepatitis B (P > 0.05) was detected. More than 40% of the hemophilic patients under 20 years of age in the present study had no immunity against hepatitis A, and 23% of hepatitis C patients had not had a hepatitis A co-infection yet. Since hepatitis A can show a fulminant course in hepatitis C patients, vaccination against hepatitis A seems necessary in hemophilic patients in the region.


Self-disclosure and its relationship to marital intimacy.
Examined the relationship between marital intimacy and self-disclosure from a multidimensional framework within a sample of 10 clinical and 10 nonclinical married couples. The linear combination of various parameters of self-disclosing behavior was able to account for 71.7% (R = .853) of the variance in intimacy ratings derived from a structured interview. Results are discussed in terms of both the role that self-disclosure plays in the development of marital intimacy and its therapeutic benefits and limitations in marital therapy.


Cost of behavioral interventions utilizing electronic drug monitoring for antiretroviral therapy adherence.
To provide data on the actual costs associated with behavioral ART adherence interventions and electronic drug monitoring used in a clinical trial to inform their implementation in future studies and real-world practice. Direct and time costs were calculated from a multisite 3-arm randomized controlled ART adherence trial. HIV-positive participants (n = 204) were randomized to standard care, enhanced counseling (EC), or EC and modified directly observed therapy (mDOT) interventions. Electronic drug monitoring (EDM) was used. Costs were calculated for various components of the 24-week adherence intervention. This economic evaluation was conducted from the perspective of an agency that may wish to implement these strategies. Sensitivity analyses were conducted to examine costs and savings associated with different scenarios. Total direct costs were $126,068 ($618 per patient). Initial time costs were $53,590 ($262 per patient). Base cost of labor was $0.36/min. EC costs for 134 patients were $18,427 ($137 per patient) and mDOT for 64 patients cost $18,638 ($291 per patient). Total per patient costs were as follows: standard care = $880, EC = $1018, EC/mDOT = $1309. Removing driving costs evidenced the most variable impact on savings between the 3 study arms. The tornado diagram (sensitivity analysis) showed a graphical representation of how each sensitivity assumption reduced costs compared with each other and the resulting comparative costs for each group. This novel economic analysis provides valuable cost information to guide treatment implementation and research design decisions.


Synthesis, structure, and antiproliferative activity of ruthenium(II) arene complexes with N,O-chelating pyrazolone-based β-ketoamine ligands.
Novel ruthenium half-sandwich complexes containing (N,O)-bound pyrazolone-based β-ketoamine ligands have been prepared, and the solid-state structures of one ligand and five complexes have been determined by single-crystal X-ray diffraction. Some of the complexes display moderate cytotoxicity toward the human ovarian cancer cell lines A2780 and A2780cisR, the latter line having acquired resistance to cisplatin.


Correlation between MRI Grading System and Surgical Findings for Lumbar Foraminal Stenosis.
Magnetic resonance imaging (MRI) grading systems using sagittal images are useful for evaluation of lumbar foraminal stenosis. We evaluated whether such a grading system is useful as a diagnostic tool for surgery. Between July 2014 and June 2015, 99 consecutive patients underwent unilateral lumbar foraminotomy for lumbar foraminal stenosis. Surgically confirmed foraminal stenosis and the contralateral, asymptomatic neuroforamen were assessed based on a 4-point MRI grading system. Two experienced researchers independently evaluated the MR sagittal images. Interobserver agreement and intraobserver agreement were analyzed using κ statistics. The mean age of patients (54 women, 45 men) was 62.5 years. A total of 101 levels (202 neuroforamens) were evaluated. MRI grades for operated neuroforamens were as follows: Grade 0 in 0.99%, Grade 1 in 5.28%, Grade 2 in 14.85%, and Grade 3 in 78.88%. Interobserver agreement was moderate for operated neuroforamens (κ=0.511) and good for asymptomatic neuroforamens (κ=0.696). Intraobserver agreement by reader 1 for operated neuroforamens was good (κ=0.776) and that for asymptomatic neuroforamens was very good (κ=0.831). In terms of lumbar level, interobserver agreement for L5-S1 (κ=0.313, fair) was relatively lower than the other level (κ=0.804, very good). MRI grading system for lumbar foraminal stenosis is thought to be useful as a diagnostic tool for surgery in the lumbar spine; however, it is less reliable for symptomatic L5-S1 foraminal stenosis than for other levels. Thus, various clinical factors as well as the MRI grading system are required for surgical decision-making.


Impact of primary care-initiated interventions promoting physical activity on body mass index: systematic review and meta-analysis.
Physical inactivity is a risk factor for obesity, overweight and for a number of chronic diseases. Although primary care may be an ideal setting to encourage people to do more exercise, there are still significant gaps in the literature on the effectiveness of primary care-initiated policies to promote physical activity. In this paper, we systematically review and meta-analyse the evidence on the impact of primary care-initiated interventions to promote exercise on the body mass index and on physical activity energy expenditure levels among people at an increased risk of having potentially disabling non-communicable diseases (but healthy enough to exercise). We find that such interventions reduce body mass index by about 0.21 kg m-2 (95% confidence interval: -0.41 to -0.01) and increase physical activity-related energy expenditure (based mostly on self-recall) by about 1.77 metabolic equivalent of task-hours a week (95% confidence interval: 0.58 to 2.95). This study suggests that primary care-initiated interventions promoting physical activity can be an effective strategy to reduce weight and increase exercise levels in this population group, although the question remains about whether such interventions can be cost-effective.


Family context and incidence of dental caries in preschool children living in areas covered by the Family Health Strategy in Salvador, Bahia State, Brazil.
Psychosocial factors influence family care and can jeopardize child development. This study aimed to analyze the association between maternal common mental disorders and incidence of early dental caries in preschool-age children living in areas covered by the Family Health Strategy in Salvador, Bahia State, Brazil, in a cohort design. A total of 472 children were examined and their mothers were interviewed from 2007 to 2008. Incidence of at least one tooth with caries was 21.19%, while 7.84% of the children showed high risk of caries. The results after adjusting for the child's age and maternal schooling showed that maternal common mental disorders were associated with high caries risk in deciduous teeth (adjusted RR = 2.41, 95%CI: 1.05-5.56, among children with 6 or fewer home appliances in the household; adjusted RR = 3.44, 95%CI: 1.06-11.17, among those that brushed twice or less per day). Maternal mental problems were associated with the development of caries in preschoolers.


Diffractometric measurements of the tonicity volume relations of human red cells in hypotonic systems.
Red cell volumes in media sufficiently hypotonic to produce partial hemolysis have been measured with a high speed hematocrit and by an improved diffraction method. A comparison of the results shows that the upward departures from the linear relation based on the van't Hoff-Mariotte law are not observed when the volumes are measured diffractometrically. Downward departures are observed at low tonicities by both methods. These results provide strong evidence that the upward departures are due to the inclusion of semirigid ghosts in the column of packed red cells which is measured when the volumes are found with the hematocrit.


The mouse Nkx2-3 homeodomain gene is expressed in gut mesenchyme during pre- and postnatal mouse development.
The Nkx homeodomain proteins are members of a growing family of known vertebrate transcription factors that are believed to play a role in cell type specification and/or maintenance of the differentiated phenotype. In this article we report on the identification and developmental expression pattern of the mouse Nkx2-3 gene. The gene is expressed primarily in gut mesoderm, dinstinct regions of the branchial arches, the tongue epithelium, and limited domains in the developing jaws, possibly including tooth anlagen. In contrast to the chicken and Xenopus genes, Nkx2-3 expression in the mouse was not observed in the developing heart or neural tube. Thus, although structurally related to chicken and Xenopus Nkx2-3, the mouse gene exhibits an overlapping but distinct expression pattern that may suggest the existence of additional family members, as yet unidentified, in vertebrate organisms.


Transcriptome analysis of the two unrelated fungal β-lactam producers Acremonium chrysogenum and Penicillium chrysogenum: Velvet-regulated genes are major targets during conventional strain improvement programs.
Cephalosporins and penicillins are the most frequently used β-lactam antibiotics for the treatment of human infections worldwide. The main industrial producers of these antibiotics are Acremonium chrysogenum and Penicillium chrysogenum, two taxonomically unrelated fungi. Both were subjects of long-term strain development programs to reach economically relevant antibiotic titers. It is so far unknown, whether equivalent changes in gene expression lead to elevated antibiotic titers in production strains. Using the sequence of PcbC, a key enzyme of β-lactam antibiotic biosynthesis, from eighteen different pro- and eukaryotic microorganisms, we have constructed a phylogenetic tree to demonstrate the distant relationship of both fungal producers. To address the question whether both fungi have undergone similar genetic adaptions, we have performed a comparative gene expression analysis of wild-type and production strains. We found that strain improvement is associated with the remodeling of the transcriptional landscape in both fungi. In P. chrysogenum, 748 genes showed differential expression, while 1572 genes from A. chrysogenum are differentially expressed in the industrial strain. Common in both fungi is the upregulation of genes belonging to primary and secondary metabolism, notably those involved in precursor supply for β-lactam production. Other genes not essential for β-lactam production are downregulated with a preference for those responsible for transport processes or biosynthesis of other secondary metabolites. Transcriptional regulation was shown to be an important parameter during strain improvement in different organisms. We therefore investigated deletion strains of the major transcriptional regulator velvet from both production strains. We identified 567 P. chrysogenum and 412 A. chrysogenum Velvet target genes. In both deletion strains, approximately 50% of all secondary metabolite cluster genes are differentially regulated, including β-lactam biosynthesis genes. Most importantly, 35-57% of Velvet target genes are among those that showed differential expression in both improved industrial strains. The major finding of our comparative transcriptome analysis is that strain improvement programs in two unrelated fungal β-lactam antibiotic producers alter the expression of target genes of Velvet, a global regulator of secondary metabolism. From these results, we conclude that regulatory alterations are crucial contributing factors for improved β-lactam antibiotic titers during strain improvement in both fungi.


An Expert Diagnosis System for Parkinson Disease Based on Genetic Algorithm-Wavelet Kernel-Extreme Learning Machine.
Parkinson disease is a major public health problem all around the world. This paper proposes an expert disease diagnosis system for Parkinson disease based on genetic algorithm- (GA-) wavelet kernel- (WK-) Extreme Learning Machines (ELM). The classifier used in this paper is single layer neural network (SLNN) and it is trained by the ELM learning method. The Parkinson disease datasets are obtained from the UCI machine learning database. In wavelet kernel-Extreme Learning Machine (WK-ELM) structure, there are three adjustable parameters of wavelet kernel. These parameters and the numbers of hidden neurons play a major role in the performance of ELM. In this study, the optimum values of these parameters and the numbers of hidden neurons of ELM were obtained by using a genetic algorithm (GA). The performance of the proposed GA-WK-ELM method is evaluated using statical methods such as classification accuracy, sensitivity and specificity analysis, and ROC curves. The calculated highest classification accuracy of the proposed GA-WK-ELM method is found as 96.81%.


[A case of traumatic chiasmal syndrome presenting with bitemporal upper quadrantanopsia].
A 22-year-old woman was involved in a motor vehicle accident and suffered a craniofacial injury. The patient was treated conservatively with a diagnosis of cerebral contusion in the frontal base confirmed with MR images. When the patient regained consciousness one week after the accident, she had a complete form of bitemporal upper quadrantanopia. A bone window level CT scan showed a linear fracture in the middle of the frontal base running longitudinally and extending posteriorly down to the sella turcica and clivus. Axial MR images parallel to the optic pathway revealed a T2 bright lesion in the anterior half of the optic chiasm. The patient recovered gradually and returned to her previous life-style six months later without complaining of diplopia, but her visual field defect was left unchanged. Traumatic chiasmal syndrome is rare and usually presents bitemporal hemianopsia. Very rarely, bitemporal quadrantanopsia has been reported. Given the anatomical structure that the neural fibers from the lower nasal part of the retina run posteriorly in the optic nerve and cross the anterior half of the optic chiasm to enter the contralateral optic tract, the lesion in the optic chiasm seen in the MR images seemed to be the causative lesion of bitemporal upper quadrantanopsia in our patient. The optic chiasm appeared to be injured by a laterally stretching force exerted in an antero-posterior direction when the medial basal fracture occurred.


Diuretic effect of furosemide in acute glomerulonephritis.
Twenty-five children with the diagnosis of acute glomerulonephritis were treated with oral or intravenous doses of furosemide. The intravenous administration of 1 mg/kg or greater resulted in an increase in urine volume in all patients. Oral doses of less than 2 mg/kg were not as effective, but there was wide variation in diuretic response to the drug. In 13 patients, plasma concentrations of furosemide were measured. The plasma half-life varied from 2.3 to 4.4 hours after intravenous administration of the drug. The plasma concentration of furosemide did not correlate with diuretic response.


A new immobilized cell system with protection against toxic solvents.
A new immobilized cell system providing protection against toxic solvents was investigated so that normal fermentations could be carried out in a medium containing toxic solvents. The system consists of immobilized growing cells in Ca-alginate gel beads to which vegetable oils, which are inexpensive absorbents of solvents, had been added. The ethanol fermentation of Saccharomyces cerevisiae ATCC 26603 was used as a model fermentation to study the protection afforded by the system against solvent toxicities. The fermentation was inhibited by solvents such as 2-octanol, benzene, toluene, and phenol. Ethanol production of one batch was not finished even after 35 h using immobilized growing yeast cells in conventional Ca-alginate gel beads in an ethanol production medium (5% glucose) containing 0.1% 2-octanol, which is used as a solvent for liquid-liquid extraction and is one of the most toxic solvents in our experiments. With the new immobilized growing cell system using vegetable oils, however, four repeated batch fermentations were completed in 35 h. Castor oil provided even more protection than soy bean, olive, and tung oils, and it was possible to complete six repeated batches in 35 h. The immobilized cell system with vegetable oils also provided protection against other toxic solvents such as benzene and toluene. A possible mechanism for the protective function of the new immobilized cell system is discussed.


[Improving medical students' interactive competence].
We report a new curriculum for improving medical students' interactive competence. The curriculum is based on the method of "psychotherapeutic plan analysis" by F. Caspar in combination with elements of systemic supervision and problem-based learning. For evaluation, participants (fifth year medical students, n = 50) were asked to fill in a questionnaire adapted to the contents of the course. Comparison was made possible by a control group (n = 72) teached in a traditional manner. Evaluation showed significant improvement of the students' self awareness, perception of their patients and sensibility for patients' needs. The students expanded their capability to reflect own actions and to work in teams. Initially expressed anxiety concerning contact with patients was reduced significantly during the course. In three and twelve months follow-ups, students still considered their personal achievement to be significantly high. Participants of the curriculum rated their courses higher with regard to didactic issues, improvement of interactive competences and personal relevance, while control courses were seen to be more relevant to prepare for exams.


Introduction. Speciation in plants and animals: pattern and process.
Although approximately 150 years have passed since the publication of On the origin of species by means of natural selection, the definition of what species are and the ways in which species originate remain contentious issues in evolutionary biology. The biological species concept, which defines species as groups of interbreeding natural populations that are reproductively isolated from other such groups, continues to draw support. However, there is a growing realization that many animal and plant species can hybridize with their close relatives and exchange genes without losing their identity. On occasion, such hybridization can lead to the origin of new species. A key to understanding what species are and the ways in which they originate rests to a large extent on a detailed knowledge of the nature and genetics of factors that limit gene flow between species and the conditions under which such isolation originates. The collection of papers in this issue addresses these topics and deals as well with some specific issues of hybrid speciation and the causes of species radiations. The papers included arise from a 1-day symposium on speciation held during the Sixth Biennial Meeting of the Systematics Association at Edinburgh in August 2007. In this introduction, we provide some background to these papers and highlight some key points made. The papers make clear that highly significant advances to our understanding of animal and plant speciation are currently being made across the range of this topic.


An optimization-based study of equivalent circuit models for representing recordings at the neuron-electrode interface.
Extracellular neuroelectronic interfacing is an emerging field with important applications in the fields of neural prosthetics, biological computation, and biosensors. Traditionally, neuron-electrode interfaces have been modeled as linear point or area contact equivalent circuits but it is now being increasingly realized that such models cannot explain the shapes and magnitudes of the observed extracellular signals. Here, results were compared and contrasted from an unprecedented optimization-based study of the point contact models for an extracellular "on-cell" neuron-patch electrode and a planar neuron-microelectrode interface. Concurrent electrophysiological recordings from a single neuron simultaneously interfaced to three distinct electrodes (intracellular, "on-cell" patch, and planar microelectrode) allowed novel insights into the mechanism of signal transduction at the neuron-electrode interface. After a systematic isolation of the nonlinear neuronal contribution to the extracellular signal, a consistent underestimation of the simulated suprathreshold extracellular signals compared to the experimentally recorded signals was observed. This conclusively demonstrated that the dynamics of the interfacial medium contribute nonlinearly to the process of signal transduction at the neuron-electrode interface. Further, an examination of the optimized model parameters for the experimental extracellular recordings from sub- and suprathreshold stimulations of the neuron-electrode junctions revealed that ionic transport at the "on-cell" neuron-patch electrode is dominated by diffusion whereas at the neuron-microelectrode interface the electric double layer (EDL) effects dominate. Based on this study, the limitations of the equivalent circuit models in their failure to account for the nonlinear EDL and ionic electrodiffusion effects occurring during signal transduction at the neuron-electrode interfaces are discussed.


[Morphofunctional characteristics of serotonin-like neurons in the hypothalamus of rats in ontogeny].
An attempt has been made to reveal 5-HT immunopositive (IP) neurones in the hypothalamus of intact foetuses (18th day of gestation) and neonatal (9-day) rats under normal conditions and after their treatment with drugs involved into 5-HT metabolism or into regulation of its uptake by serotoninergic neurones. 5-HTIP cells were not observed in intact animals as well as after L-tryptophan treatment, whereas two large colonies of these neurones were found in the anterio-lateral hypothalamus and dorsomedial nucleus after subsequent injections of monoamine oxidase inhibitor, pargyline, and amino acid precursor of 5-HT synthesis, L-tryptophan. Significantly less intensive reaction was observed after injections of another precursor of 5-HT synthesis, 5-hydroxytryptophan, or pargyline only. Immunostaining evoked by pargyline or L-tryptophan can be prevented by preliminary injections of fluoxetine, a specific inhibitor of 5-HT uptake by serotoninergic neurones. These data suggest that the immunostaining of hypothalamic neurones is due to their capacity to take up specifically 5-HT from the environment rather than to its intraneuronal synthesis from L-tryptophan. However, 5-HT synthesis from 5-hydroxytryptophan in the same cells may also take place. The uptake of extracellular 5-HT by catecholaminergic neurones is absent, since nomifensine, a specific inhibitor of this uptake, does not affect immunostaining.


Increased serum levels of Galectin-9 in patients with chronic lymphocytic leukemia.
Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in adults. Despite improvements in treatment, CLL is still considered an incurable disease. The aim of the present study was to evaluate galectin-1, -3 and -9 (Gal-1, -3 and -9) and Gal-3 binding protein (Gal-3BP) as prognostic and predictive factors in patients with CLL. Serum concentrations of Gal-1, -3 and -9 and Gal-3BP were measured in 48 patients with CLL and 30 control patients, using multiplex bead arrays. In patients with CLL, galectin concentrations were assessed prior to, during and following treatment. In patients with CLL who were untreated, galectin concentrations were measured twice with a 6-month interval. The serum level of Gal-9 was significantly increased (P<0.0001) in patients with CLL compared with the control group, and was associated with the clinical stage according to Binet classification, as well as poor cytogenetic and serum CLL prognostic factors. In addition, patients with CLL, who exhibited treatment failure, exhibited higher concentrations of Gal-9 (P=0.06) and Gal-3BP (P=0.009) at the end of the treatment when compared with patients under complete remission or stabilization of the disease. The serum level of Gal-3 was significantly decreased (P=0.012) in patients with CLL compared with the control group. These results suggest that Gal-9 is a potential prognostic factor in patients with CLL. The predictive value of Gal-9 requires further study in larger cohorts of patients.


Stability and change in externalising behaviours.
This paper provides an overview of a series of issues relating to continuity and discontinuity in externalising disorders including conduct disorder, attention deficit disorder and substance use disorders in childhood and adolescence. These issues include: (a) the assessment of stability and change; (b) the origins of behavioural stability; (c) the origins of behavioural change; and (d) the preventive and clinical implications of research into behavioural stability and change. It is concluded that future research into this area should involve: (a) further research into the genetic factors underlying externalising disorders; (b) continued research into the developmental progressions; (c) refinement and revision of measurement methodologies; and (d) greater use of designed experimentation to examine the extent to which externalising behaviours are amenable to change through both public health and clinical interventions.


Neurocysticercosis case with tuberculoma-like epithelioid granuloma strongly suspected by serology and confirmed by mitochondrial DNA.
An Indian woman with multiple and nodular cerebral lesions presenting epithelioid granulomas was diagnosed as suspected malignant tumours and the biopsy was carried at local hospital in Japan. The specimen was pathologically diagnosed as tuberculoma. However, due to her nationality, the authors suspected it to be neurocysticercosis (NCC) and carried out serology and applied mitochondrial DNA analysis of Taenia solium. These diagnostic tools revealed it as NCC radiologically and pathologically mimicking central nervous tuberculomas. Molecular confirmation of NCC cases is strongly recommended when we can get the biopsy specimens.


Cinnamon bark extract improves glucose metabolism and lipid profile in the fructose-fed rat.
The present study was designed to investigate whether cinnamon bark extract (CBEt) mitigates the adverse effects of fructose loading on glucose metabolism and lipid profile in rats. Adult male albino rats of body weight 150-170 g were divided into five groups and fed with either control or high fructose diet (HFD). CBEt was administered to HFD-fed rats orally at two doses (a low and a high dose) while the control diet-fed rats were treated with a high dose of CBEt. The treatment protocol was carried out for 60 days after which the oral glucose tolerance test was carried out. Biochemical parameters related to glucose metabolism and lipid profile were assayed. The levels of glucose, insulin and protein-bound sugars were higher and activities of enzymes of glucose metabolism were altered in HFD-fed rats, as compared to control animals. The levels were brought back to near-normal when administered with CBEt at high dose. CBEt also prevented the hyperlipidaemia observed in fructose-fed rats and improved glucose tolerance. CBEt did not show any significant effect in fructose-fed rats when administered at low dose. These findings indicate the improvement of glucose metabolism in-vivo by CBEt in fructose-fed rats.


GENETIC DRIFT AND FOUNDER EFFECT IN NATIVE VERSUS INTRODUCED POPULATIONS OF AN INVADING PLANT, LYTHRUM SALICARIA (LYTHRACEAE).
There are few convincing examples of genetic drift at loci under selection in natural populations. The plant sexual polymorphism tristyly provides an opportunity to investigate genetic drift because stochastic processes interacting with frequency-dependent selection give rise to a diagnostic pattern of morph-frequency variation. A previous study of 102 Ontario populations of the introduced tristylous wetland herb Lythrum salicaria provided evidence for the role of stochastic processes during colonization. However, whether stochastic effects are greater in these recently introduced populations compared to native Eurasian populations remains unclear. The propensity of this species to invade disturbed habitats suggests that episodes of colonization and periods of small population size must also occur in the native range. A survey of 102 populations in southwestern France indicated reduced stochastic effects in native populations. Populations exhibited significantly lower morph loss than in Ontario (5% vs. 23%) and significantly higher values of morph evenness. The greater incidence of trimorphism in French populations was not associated with larger population sizes; populations were significantly smaller than those in Ontario (means: 266 vs. 487). Morph evenness was positively correlated with population size among French but not Ontario populations, providing further evidence of nonequilibrium conditions in introduced compared to native populations. The incidence of trimorphism was unexpectedly high in small native populations (N ≤ 25; 22 of 27 populations trimorphic). Computer simulations indicated that levels of gene flow on the order of m ≥ 0.05 can account for the maintenance of tristyly in small populations. The high connectivity of populations within the agricultural landscape typical of southwestern France may facilitate levels of gene flow sufficient to maintain trimorphism in small populations.


Long-term neurodevelopmental outcome in conservatively treated congenital hyperinsulinism.
Congenital hyperinsulinism (CH) is treated surgically in many centers (near-total and partial pancreatectomy for diffuse and focal disease respectively). Most patients treated with near-total pancreatectomy developed diabetes during childhood/puberty. CH patients are at increased risk of neurodevelopmental disorders, some being severe, which are reported to occur in 14-44% of patients from highly heterogenous cohorts. Over the last few decades, we have treated children with CH conservatively without surgery. The aim of this study was to assess the neurodevelopmental outcome of these patients. The study included 21 Ashkenazi CH medically treated patients: 11 homozygotes (diffuse disease) and 9 heterozygotes with mutations on the paternal allele (presumed focal disease). The mean age was 13.7 years (range 8-23). Neurodevelopmental outcomes were assessed by telephone interviews of parents, using a standard questionnaire. Closest age siblings of CH patients served as controls. Ten CH patients had perinatal seizures of short duration. Four had post-neonatal seizures, which remitted entirely. During early childhood, four patients (19%) had hypotonia, eight (38%) had fine motor problems, seven (33%) had gross motor problems (clumsiness), and one had mild cerebral palsy. Three patients (14%) had speech problems. Eight patients required developmental therapy, compared to one in the control group. Most of these problems were resolved by age 4-5 years. At school age, all were enrolled in regular education, some excelled in their studies, 6 out of 21 patients (29%) had learning problems (2 out of 21 controls). None had overt diabetes. Good neurodevelopmental outcome was observed in our conservatively treated CH patients, with no diabetes as reported in patients undergoing pancreatectomy.


Out-of-hospital cardiac arrest: determinant factors for immediate survival after cardiopulmonary resuscitation.
to analyze determinant factors for the immediate survival of persons who receive cardiopulmonary resuscitation from the advanced support units of the Mobile Emergency Medical Services (SAMU) of Belo Horizonte. this is a retrospective, epidemiological study which analyzed 1,165 assistance forms, from the period 2008 - 2010. The collected data followed the Utstein style, being submitted to descriptive and analytical statistics with tests with levels of significance of 5%. the majority were male, the median age was 64 years, and the ambulance response time, nine minutes. Immediate survival was observed in 239 persons. An association was ascertained of this outcome with "cardiac arrest witnessed by persons trained in basic life support" (OR=3.49; p<0.05; CI 95%), "cardiac arrest witnessed by Mobile Emergency Medical Services teams" (OR=2.99; p<0.05; CI95%), "only the carry out of basic life support" (OR=0.142; p<0.05; CI95%), and "initial cardiac rhythm of asystole" (OR=0.33; p<0.05; CI 95%). early access to cardiopulmonary resuscitation was related to a favorable outcome, and the non-undertaking of advanced support, and asystole, were associated with worse outcomes. Basic and advanced life support techniques can alter survival in the event of cardiac arrest.


Colonoscopy attachments for the detection of precancerous lesions during colonoscopy: A review of the literature.
Although colonoscopy has been proven effective in reducing the incidence of colorectal cancer through the detection and removal of precancerous lesions, it remains an imperfect examination, as it can fail in detecting up to almost one fourth of existing adenomas. Among reasons accounting for such failures, is the inability to meticulously visualize the colonic mucosa located either proximal to haustral folds or anatomic curves, including the hepatic and splenic flexures. In order to overcome these limitations, various colonoscope attachments aiming to improve mucosal visualization have been developed. All of them - transparent cap, Endocuff, Endocuff Vision and Endorings - are simply mounted onto the distal tip of the scope. In this review article, we introduce the rationale of their development, present their mode of action and discuss in detail the effect of their implementation in the detection of lesions during colonoscopy.


Fertility in Advanced Societies: A Review of Research: La fécondité dans les sociétés avancées: un examen des recherches.
This paper provides a review of fertility research in advanced societies, societies in which birth control is the default option. The central aim is to provide a comprehensive review that summarizes how contemporary research has explained ongoing and expected fertility changes across time and space (i.e., cross- and within-country heterogeneity). A secondary aim is to provide an analytical synthesis of the core determinants of fertility, grouping them within the analytical level in which they operate. Determinants are positioned at the individual and/or couple level (micro-level), social relationships and social networks (meso-level); and, by cultural and institutional settings (macro-level). The focus is both on the quantum and on the tempo of fertility, with a particular focus on the postponement of childbearing. The review incorporates both theoretical and empirical contributions, with attention placed on empirically tested research and whether results support or falsify existing theoretical expectations. Attention is also devoted to causality and endogeneity issues. The paper concludes with an outline of the current challenges and opportunities for future research.


Is boundary extension emotionally selective?
When they have to memorize a picture, people usually build a memory trace including more extensive boundaries than the original picture, a phenomenon known as boundary extension or BE. This article looks at whether the emotion category expressed (i.e., happiness, pleasure, irritation, or anger) by actors in short films could have an influence on the BE effect. The results showed that positively valenced emotions (happiness, pleasure) led to an extension effect, while the negatively valenced ones (anger, irritation) did not produce any significant memory distortion. The arousal dimension of emotions had no significant effect on BE. The current results were discussed in the light of previous studies on the links between BE and emotions.


The Clinical Efficacy of Minimally Invasive Clamp-Assisted Reduction and Open Reduction with Wire Cerclage for Unstable Subtrochanteric Fractures.
The purpose of this study was to compare the clinical effectiveness of minimally invasive clamp-assisted reduction and open reduction with wire cerclage and intramedullary nails for unstable subtrochanteric fractures. Between January 2016 and October 2019, 68 patients who had unstable subtrochanteric fractures experienced intramedullary nail surgery in this retrospective study. There were 41 cases in the minimally invasive clamp or closed reduction group (group A) and 27 cases in the open reduction with wire cerclage group (group B). There were 3 cases of complications in group A and 2 cases of complications in group B. Remarkable distinction was observed between the two groups in the operation time (p < 0.05), quality of reduction (p < 0.05), and union time (p < 0.05). For the successful surgical treatment of unstable femoral subtrochanteric fractures, an anatomical reduction is crucial. Reduction and wire cerclage are cut to give medial support for the anatomical reduction, which has a positive effect on fracture healing.


The problem of rigor in qualitative research.
There are few explicit discussions in nursing literature of how qualitative research can be made as rigorous as it is relevant to the perspective and goals of nursing. Four factors complicate the debate about the scientific merits of qualitative research: the varieties of qualitative methods, the lack of clear boundaries between quantitative and qualitative research, the tendency to evaluate qualitative research against conventional scientific criteria of rigor, and the artistic features of qualitative inquiry. A framework for understanding the similarities and differences in research approaches and a summary of strategies to achieve rigor in qualitative research are presented.


Fabrication of extended-dissolution divalproex tablets: a green solvent-free granulation technique.
Objective: Divalproex sodium (DVS) is a challenging drug owing to its hygroscopicity, bitter taste, and short in vivo half-life. This study aims to produce stable taste masked DVS once daily tablets using solvent free hot melt granulation (HMG) process.Methods: A lab scale high shear mixer granulator employing six meltable lipid binders (compritol®888 ATO, beeswax, gelucire®50/13, precirol® ATO5, stearyl alcohol, and geleol®) was used for the preparation of tablets. Quality control tests were performed on granules and tablets, and Box-Behnken's design was adopted to investigate the effect of binder concentration, impeller speed, and granulation time on the drug dissolution. Shelf and accelerated stability evaluation, taste assessment, and in vivo pharmacokinetic study were conducted on the selected batches.Results: Results revealed that DVS tablets were successfully prepared, and that the in vitro dissolution of the drug was inversely proportional to the binder concentration. Beeswax and compritol® tablets showed similar dissolution profiles to the marketed product Depakote® 500 ER tablets (F1 < 15 and F2 > 50). The selected batches showed lower moisture content (<2%) and successfully masked the bitter taste compared to uncoated tablets based on a hydrophilic matrix. The in vivo pharmacokinetic study delineated relative bioavailability values for Beeswax and Compritol® tablets of 95.6% and 118%, respectively, compared to the marketed product.Conclusion: The solvent free HMG process can be employed to formulate 24 h extended dissolution DVS tablets with masked bitter taste and high stability, and comparable or higher bioavailability than the marketed product.


Eight drugs in one day chemotherapy for brain tumors: experience in 107 children and rationale for preradiation chemotherapy.
The development of a new multidrug chemotherapy regimen for primary brain tumors was based upon the cellular heterogeneity within individual tumors, the Goldie-Coldman and Price-Goldie-Hill hypotheses, and known agonistic effects of certain drug combinations and sequences. Eight drugs (vincristine [VCR], hydroxyurea, procarbazine, CCNU, cisplatin, cytosine arabinoside [Ara-C] high-dose methylprednisolone, and either cyclophosphamide or dacarbazine) were administered within 12 hours in an attempt to minimize myelosuppression. Courses were repeated at 2- to 4-week intervals. The regimen was devised to include lipid and water soluble drugs, polar and nonpolar agents, phase-specific and cell-cycle independent agents, and antineoplastics with different mechanisms of action. More than 330 courses of the regimen were administered to 107 children with brain tumors whose tumor had recurred or had been incompletely resected at diagnosis. Tumor response according to protocol-specified criteria and independent review was evaluable in 78% of the patients. After just two cycles of chemotherapy and within a 4- to 6-week interval, 50% had an objective tumor response including 15.5% who had a complete response (CR). Nephrotoxicity and high-frequency hearing losses were noted after three to five courses of therapy in approximately half of the patients. Transfusions with red cells or platelets and use of antibiotics for fever and neutropenia were required in 10% to 25% of patients. The regimen appears satisfactory for preradiation chemotherapy in newly diagnosed patients with residual tumor after surgery, but it must be compared with standard therapeutic approaches in prospective controlled trials before its relative value can be established.


The in situ infrared microspectroscopy of bacterial colonies on agar plates.
The specular reflectance infrared spectra of thirty species of bacteria were obtained in situ, without their removal from the agar growth media, using the infrared microscope. Compared to transmittance spectra obtained from dehydrated films, the transformed reflectance spectra show significant band shifts which are greater for gram positive bacteria. The most notable shift occurs in the v[a](PO2-) band which shifts 8 cm(-1) higher upon removal of water. In addition, some measure of the differentiation potential of our in situ reflectance spectra was gathered by using principal components regression as a method of discrimination. We assigned a +1 for a gram positive property and a -1 to a gram negative property for each different bacteria species. The prediction results from a cross validation show that all the gram positive bacteria retain positive values for Gram stain predictions while all the gram negative species retain their negative values, suggesting a simple marker for differentiation. Overall, using reflectance spectra from colonies directly on the agar requires no sample preparation and provides slightly better differentiating spectral information than the transmittance spectra of dehydrated films.


Multihormonal response to dexamethasone. A study in atopic dermatitis and normal controls.
Although minor disturbances of the circadian serum cortisol rhythm and diminished excretion of steroid metabolites have been reported in patients with atopic dermatitis, test assays regarding subtle neuroendocrine alterations have not been employed so far. We therefore studied the serum concentrations of cortisol, prolactin and adrenocorticotropin under baseline conditions, after 1 mg dexamethasone and after a defined methylprednisolone treatment in 15 patients with atopic dermatitis, in comparison with 10 healthy controls. The assessment of the hormones revealed no remarkable differences between either group at any of the blood sampling time points. However, in 3 patients and 2 control subjects, though exhibiting no concomitant disease, we could find no suppression of endogenous cortisol to below 5 micrograms/dl after oral intake of 1 mg dexamethasone. These cortisol non-suppressors showed lower dexamethasone serum concentrations in the morning after its administration, as compared with the suppressors. Acute (1 mg dexamethasone) or prolonged (40 mg methylprednisolone over 6 days) intake of glucocorticoids suppressed prolactin levels in both groups, demonstrating that the effect of glucocorticoids on the hormone system is not restricted to the hypothalamic-pituitary-adrenal axis. Our results indicate an intact feedback response of this hormonal axis to 1 mg dexamethasone and the ability of long-term as well as acute glucocorticoid administration to influence the prolactin secretion in patients with atopic dermatitis.


Polygenic scores for smoking and educational attainment have independent influences on academic success and adjustment in adolescence and educational attainment in adulthood.
Educational success is associated with greater quality of life and depends, in part, on heritable cognitive and non-cognitive traits. We used polygenic scores (PGS) for smoking and educational attainment to examine different genetic influences on facets of academic adjustment in adolescence and educational attainment in adulthood. PGSs were calculated for participants of the Minnesota Twin Family Study (N = 3225) and included as predictors of grades, academic motivation, and discipline problems at ages 11, 14, and 17 years-old, cigarettes per day from ages 14 to 24 years old, and educational attainment in adulthood (mean age 29.4 years). Smoking and educational attainment PGSs had significant incremental associations with each academic variable and cigarettes per day. About half of the adjusted effects of the smoking and education PGSs on educational attainment in adulthood were mediated by the academic variables in adolescence. Cigarettes per day from ages 14 to 24 years old did not account for the effect of the smoking PGS on educational attainment, suggesting the smoking PGS indexes genetic influences related to general behavioral disinhibition. In sum, distinct genetic influences measured by the smoking and educational attainment PGSs contribute to academic adjustment in adolescence and educational attainment in adulthood.


Falls in a Young Active Amputee Population: A Frequent Cause of Rehospitalization?
Falls occur in up to 50% of amputees within a single year of their operation and up to 40% of these falls result in injury. However, there is a lack of data evaluating falls in a young, active amputee population despite an estimated 58% of persons living with an amputation being under the age of 65. The authors evaluated an amputee population (n = 393) with a mean age of 25.53 years. Overall incidence, prevalence, fall characteristics, and risk factors were calculated for falls resulting in rehospitalization. An incidence of 1.92 per 1,000 person years with a prevalence of 2.04% was found with 87.5% occurring within the first 6 months following definitive amputation. Of the patients rehospitalized, 75% required at least 1 surgical procedure. Infectious complications had the most significant morbidity requiring a mean of 5 operative procedures. Those that delayed evaluation (mean = 13 days) vs. those that presented 0 to 1 day from a fall were significantly more at risk of an infectious complication (p = 0.03). This study is the first to report such a relationship, and emphasizes the need for at-risk patients to seek early medical attention as this may minimize the risk of infection and obviate the need for surgical intervention.


Spiroindimicins A-D: new bisindole alkaloids from a deep-sea-derived actinomycete.
A PCR-based screening approach led to the identification of a deep-sea-derived Streptomyces sp. SCSIO 03032 capable of producing new bisindole alkaloids spiroindimicins A-D (1-4). Structural elucidation of these compounds revealed the presence of unusual [5,6] or [5,5] spiro-ring containing skeletons. Spiroindimicins B-D (2-4) with a [5,5] spiro-ring exhibited moderate cytotoxicities against several cancer cell lines.


Safety and efficacy of calcipotriene plus betamethasone dipropionate topical suspension in the treatment of extensive scalp psoriasis in adolescents ages 12 to 17 years.
The objective of this study was to assess the safety and efficacy of the fixed combination calcipotriene 0.005% plus betamethasone dipropionate 0.064% topical suspension in adolescents with extensive scalp psoriasis. In this phase II, open-label, 8-week study, adolescents with psoriasis (ages 12-17 years) with 20% or more of the scalp area affected (at least moderate severity according to Investigator's Global Assessment [IGA]) were assigned to once-daily treatment with calcipotriene plus betamethasone dipropionate topical suspension. The primary endpoint was safety, focusing on calcium metabolism and hypothalamic-pituitary-adrenal axis function. Secondary efficacy endpoints were the proportion of patient's achieving treatment success (clear or almost clear disease according to the IGA and clear or very mild disease according to the Patient's Global Assessment [PaGA]) and percentage change in investigator-assessed Total Sign Score (TSS). Pruritus was also assessed. Overall, 31 patients received treatment. Sixteen patients (52%) experienced a total of 20 adverse events; 19 were considered unrelated to study treatment, 14 were mild, and none were serious or lesional or perilesional on the scalp. One patient showed signs of mild adrenal suppression at week 4; the patient discontinued treatment and had normal test results at follow-up 4 weeks later. No cases of hypercalcemia were reported. By treatment end, treatment success was reported for 17 patients (55%) according to the IGA and 18 (58%) according to the PGA. Mean TSS improved from 6.9 at baseline to 2.9 at treatment end (59% improvement). By week 8, 28 patients (90%) experienced mild or no itching, versus 20 (65%) at baseline. Once-daily calcipotriene plus betamethasone dipropionate topical suspension was well tolerated and efficacious for the treatment of scalp psoriasis in adolescents.


[The role of SM22 alpha in cytoskeleton organization and vascular remodeling].
Phenotypic modulation of vascular smooth muscle cells (VSMCs) plays a key role in vascular remodeling diseases, such as atherosclerosis, hypertension and restenosis. Recent researches have focused on the expression regulation of VSMC-specific marker genes and cytoskeleton organization in association with phenotypic modulation of VSMCs. Smooth muscle 22 alpha (SM22 alpha) is a novel differentiated VSMC marker, which is characterized by its smooth muscle tissue-specific and VSMC phenotype-specific expression pattern, and serves as an actin-association protein to participate in VSMC cytoskeleton organization and vascular remodeling. This article reviews recent advances in the characterization of SM22 alpha structure and its mechanism in VSMC cytoskeleton organization and vascular remodeling.


Stability of buried carbon in deep-ploughed forest and cropland soils - implications for carbon stocks.
Accumulation of soil organic carbon (SOC) may play a key role in climate change mitigation and adaptation. In particular, subsoil provides a great potential for additional SOC storage due to the assumed higher stability of subsoil SOC. The fastest way in which SOC reaches the subsoil is via burial, e.g. via erosion or deep ploughing. We assessed the effect of active SOC burial through deep ploughing on long-term SOC stocks and stability in forest and cropland subsoil. After 25-48 years, deep-ploughed subsoil contained significantly more SOC than reference subsoils, in both forest soil (+48%) and cropland (+67%). However, total SOC stocks down to 100 cm in deep-ploughed soil were greater than in reference soil only in cropland, and not in forests. This was explained by slower SOC accumulation in topsoil of deep-ploughed forest soils. Buried SOC was on average 32% more stable than reference SOC, as revealed by long-term incubation. Moreover, buried subsoil SOC had higher apparent radiocarbon ages indicating that it is largely isolated from exchange with atmospheric CO2. We concluded that deep ploughing increased subsoil SOC storage and that the higher subsoil SOC stability is not only a result of selective preservation of more stable SOC fractions.


Autologous transplant programs in community hospitals: role of centralized stem cell processing laboratories.
Transplantation of bone marrow and peripheral blood stem cells was initially limited to large, research-oriented institutions. General acceptance of autologous transplantation has grown rapidly in recent years and there is now interest in the establishment of autologous transplant programs in community hospitals. However, the lack of facilities to process and cryopreserve stem cells can be a major obstacle to small transplant programs. In response to this problem, we suggest that a centralized stem cell processing facility can offer the required services to several hospitals within a metropolitan area. The establishment of processing facilities within currently existing blood banks and blood centers is a logical extension of their current roles in hematotherapy. In this paper, we describe the operation of one such centralized processing facility.


Research on Domain-Specific Knowledge Graph Based on the RoBERTa-wwm-ext Pretraining Model.
The purpose of this study is to solve the effective way of domain-specific knowledge graph construction from information to knowledge. We propose the deep learning algorithm to extract entities and relationship from open-source intelligence by the RoBERTa-wwm-ext pretraining model and a knowledge fusion framework based on the longest common attribute entity alignment technology and bring in different text similarity algorithms and classification algorithms for verification. The experimental research showed that the named entity recognition model using the RoBERTa-wwm-ext pretrained model achieves the best results in terms of recall rate and F1 value, first, and the F value of RoBERTa-wwm-ext + BiLSTM + CRF reached up to 83.07%. Second, the RoBERTa-wwm-ext relationship extraction model has achieved the best results; compared with the relation extraction model based on recurrent neural network, it is improved by about 20%∼30%. Finally, the entity alignment algorithm based on the attribute similarity of the longest common subsequence has achieved the best results on the whole. The findings of this study provide an effective way to complete knowledge graph construction in domain-specific texts. The research serves as a first step for future research, for example, domain-specific intelligent Q&A.


Light-limited growth rate modulates nitrate inhibition of dinitrogen fixation in the marine unicellular cyanobacterium Crocosphaera watsonii.
Biological N2 fixation is the dominant supply of new nitrogen (N) to the oceans, but is often inhibited in the presence of fixed N sources such as nitrate (NO3-). Anthropogenic fixed N inputs to the ocean are increasing, but their effect on marine N2 fixation is uncertain. Thus, global estimates of new oceanic N depend on a fundamental understanding of factors that modulate N source preferences by N2-fixing cyanobacteria. We examined the unicellular diazotroph Crocosphaera watsonii (strain WH0003) to determine how the light-limited growth rate influences the inhibitory effects of fixed N on N2 fixation. When growth (µ) was limited by low light (µ = 0.23 d-1), short-term experiments indicated that 0.4 µM NH4+ reduced N2-fixation by ∼90% relative to controls without added NH4+. In fast-growing, high-light-acclimated cultures (µ = 0.68 d-1), 2.0 µM NH4+ was needed to achieve the same effect. In long-term exposures to NO3-, inhibition of N2 fixation also varied with growth rate. In high-light-acclimated, fast-growing cultures, NO3- did not inhibit N2-fixation rates in comparison with cultures growing on N2 alone. Instead NO3- supported even faster growth, indicating that the cellular assimilation rate of N2 alone (i.e. dinitrogen reduction) could not support the light-specific maximum growth rate of Crocosphaera. When growth was severely light-limited, NO3- did not support faster growth rates but instead inhibited N2-fixation rates by 55% relative to controls. These data rest on the basic tenet that light energy is the driver of photoautotrophic growth while various nutrient substrates serve as supports. Our findings provide a novel conceptual framework to examine interactions between N source preferences and predict degrees of inhibition of N2 fixation by fixed N sources based on the growth rate as controlled by light.


Neuropsychological testing for the assessment of manganese neurotoxicity: a review and a proposal.
Manganese exposure can cause neurobehavioral and neurological signs and symptoms. A review of the literature was carried out in order to identify the most sensitive and effective methods to assess these outcomes. Studies on manganese exposure performed with neuropsychological tests were reviewed using Medline. Test methods, obtained outcomes, and dose-response relationships were considered. Based on the review and additional considerations, a testing battery for adult and children was identified. A total number of 31 studies were reviewed and divided in 18 occupational, 7 environmental, and 6 on children. A large variety of tests exploring motor and cognitive functions and mood were applied. Neurobehavioral effects were dose-dependent in several studies and determined by much lower exposure levels compared to 1 mg Mn/m(3) in total dust which is considered to be the minimum concentration able to induce the classical clinical features of "manganism." Although through a wide variety of tests, the observed outcomes support the knowledge that manganese exposure can cause neurobehavioral effects. Motor functions are mainly affected in adults, and cognitive functions and behavior are more affected in children. Literature on manganese neurobehavioral effect is quite consistent, however, further improvement may be achieved by using better structured and more comparable evaluation methods. Based on the analysis of the existing experiences a test battery including tests of motor functions, response speed, cognitive functions, intellectual abilities, mood, and symptom questionnaires is suggested. We recommend that the tests indicated should always be included in future studies as a core battery.


Identification of new antigen candidates for the early diagnosis of Mycobacterium avium subsp. paratuberculosis infection in goats.
Currently Mycobacterium avium subsp. paratuberculosis (MAP) infection is diagnosed through indirect tests based on the immune response induced by the infection. The antigens commonly used in IFN-γ release assays (IGRA) are purified protein derivative tuberculins (PPD). However, PPDs, lack both specificity (Sp) and sensitivity (Se) in the early phase of infection. This study investigated the potential of 16 MAP recombinant proteins and five lipids to elicit the release of IFN-γ in goats from herds with or without a history of paratuberculosis. Ten recombinant proteins were selected as potential candidates for the detection of MAP infection in young goats. They were found to detect 25 to 75% of infected shedder (IS) and infected non-shedder (INS) kids younger than 10months of age. In comparison, PPD was shown to detect only 10% of INS and no IS kids. For seven antigens, Se (21-33%) and Sp (≥90%) of IGRA were shown to be comparable with PPD at 20months old. Only three antigens were suitable candidates to detect IS adult goats, although Se was lower than that obtained with PPD. In paratuberculosis-free herds, IGRA results were negative in 97% of indoor goats and 86% of outdoor goats using the 10 antigens. However, 22 to 44% of one-year-old outdoor goats were positive suggesting that they may be infected. In conclusion, this study showed that ten MAP recombinant proteins are potential candidates for early detection of MAP infected goats. Combining these antigens could form a possible set of MAP antigens to optimize the Se of caprine IGRA.


Hemodynamic and Light-Scattering Changes of Rat Spinal Cord and Primary Somatosensory Cortex in Response to Innocuous and Noxious Stimuli.
Neuroimaging technologies with an exceptional spatial resolution and noninvasiveness have become a powerful tool for assessing neural activity in both animals and humans. However, the effectiveness of neuroimaging for pain remains unclear partly because the neurovascular coupling during pain processing is not completely characterized. Our current work aims to unravel patterns of neurovascular parameters in pain processing. A novel fiber-optic method was used to acquire absolute values of regional oxy- (HbO) and deoxy-hemoglobin concentrations, oxygen saturation rates (SO₂), and the light-scattering coefficients from the spinal cord and primary somatosensory cortex (SI) in 10 rats. Brief mechanical and electrical stimuli (ranging from innocuous to noxious intensities) as well as a long-lasting noxious stimulus (formalin injection) were applied to the hindlimb under pentobarbital anesthesia. Interhemispheric comparisons in the spinal cord and SI were used to confirm functional activation during sensory processing. We found that all neurovascular parameters showed stimulation-induced changes; however, patterns of changes varied with regions and stimuli. Particularly, transient increases in HbO and SO₂ were more reliably attributed to brief stimuli, whereas a sustained decrease in SO₂ was more reliably attributed to formalin. Only the ipsilateral SI showed delayed responses to brief stimuli. In conclusion, innocuous and noxious stimuli induced significant neurovascular responses at critical centers (e.g., the spinal cord and SI) along the somatosensory pathway; however, there was no single response pattern (as measured by amplitude, duration, lateralization, decrease or increase) that was able to consistently differentiate noxious stimuli. Our results strongly suggested that the neurovascular response patterns differ between brief and long-lasting noxious stimuli, and can also differ between the spinal cord and SI. Therefore, a use of multiple-parameter strategy tailored by stimulus modality (brief or long-lasting) as well as region-dependent characteristics may be more effective in detecting pain using neuroimaging technologies.


On the hypes and falls in neuroprotection: targeting the NMDA receptor.
Activation of the NMDA (N-methyl-D-aspartate) responsive subclass of glutamate receptors is an important mechanism of excitatory synaptic transmission. Moreover, NMDA receptors are widely involved in many forms of synaptic plasticity such as long-term potentiation (LTP) and long-term depression (LTD), which are thought to underlie complex tasks, including learning and memory. Dysfunction of these ligand-gated cation channels has been identified as an underlying molecular mechanism in neurological disorders ranging from acute stroke to chronic neurodegeneration in amyotrophic lateral sclerosis. Excessive glutamate levels have been detected following brain trauma and cerebral ischemia, resulting in an unregulated stimulation of NMDA receptors. These conditions are thought to elicit a cascade of excitation-mediated neuronal damage where massive increases in intracellular calcium concentrations finally trigger neuronal damage and apoptosis. Consistent with the hypothesis of NMDA receptors as essential mediators of excitotoxicity, the different functional domains of these ion channels have been identified as potential targets for neuroprotective agents. Following an initial hype on potential NMDA receptor therapeutics, the authors currently see a period of skepticism that, in reverse, appears to neglect the therapeutic potential of this receptor class. This review attempts a reappraisal of this important class of neurotransmitter receptors, with a focus on NMDA receptor heterogeneity, ligand binding domains, and candidate diseases for a potential neuroprotective therapy.


Multiple DNA elements determine basal and thyroid hormone regulated expression of the human glycoprotein alpha subunit gene in pituitary cells.
Basal and thyroid hormone-regulated expression of constructs containing varying lengths of 5' flanking sequence of the human glycoprotein hormone alpha subunit gene ligated to the reporter gene encoding chloramphenicol acetyl transferase (CAT) were examined in transfected pituitary GH3 cells. CAT gene expression was quantified by measurement of CAT enzyme activity. In addition, an RNase protection assay was used to confirm changes in CAT mRNA levels and to verify regulation of transcription from the authentic alpha gene start site. The pattern of basal alpha promoter activity indicated the presence of inhibitory DNA elements between -98 and -172 and upstream of -846 relative to the transcriptional start site, as well as a stimulatory element between -346 and -846. Each of the transfected constructs exhibited tri-iodothyronine inhibition of alpha promoter activity, suggesting the presence of an inhibitory thyroid hormone response element within 98 bp of the alpha gene transcriptional start site.


[Radical cystectomy for invasive bladder carcinoma in patients 75 years old or older].
Between 1995 and 2004, 43 patients underwent radical cystectomy and urinary diversion for the treatment of invasive bladder cancer at our institution. Of these patients, seven who were 75 years old or older, were considered elderly. Survival and treatment outcome of these patients were compared to younger counterparts stratified into three groups by age at diagnosis (12 patients younger than 64, 12 patients 65 to 69 years, and 12 patients 70 to 74 years). Preoperative morbidity was encountered in 57% of the elderly patients, and 42% of the elderly patients had two or more complications. There was one operative death (14%) among the elderly patients but no such deaths in the 3 younger groups. The postoperative complication rate for patients age 75 years or older was 86%, compared to 75% for patients younger than 64, 75% for those age 65 to 69 and 83% for those age 70-74. The prevalence did not differ significantly between the older and youger patients. There were no cancer deaths among the elderly patients, but 8 of the 36 younger patients died of cancer. The cancer-specific 5-year survival rate was 100% at 34 months in the elderly population. These findings suggest that radical cystectomy and urinary diversion is a relatively safe procedure and a curative operation is worth attempting in elderly patients with invasive bladder cancer, if they are in generally good health.


Salvaging fractured porcelain crowns with a direct composite repair technique.
Fractures of porcelain crowns, particularly on anterior teeth, require a rapid resolution. While repair can be achieved with relative ease using a composite resin material, detailed investigation of the cause of the fracture is mandatory to avoid repetition, and to safeguard longevity of both the affected restoration and abutment tooth. Treatment of fractured prostheses should not be implemented unless thorough evaluation is performed to determine potential damage to abutment and surrounding teeth. The ensuing discussion highlights etiology, clinical presentations, and guidelines for repairing fractured restorations.


Heavy metal contamination and metallothionein mRNA in blood and feathers of Black-tailed gulls (Larus crassirostris) from South Korea.
The objectives of this study were to determine levels of heavy metal in the feathers and blood of Black-tailed gulls (Larus crassirostris), to evaluate metallothionein (MT) mRNA level in Black-tailed gulls on three independent islets, and to examine the correlation between heavy metal concentrations and MT mRNA expression. Eleven heavy metals (Al, Cd, Mn, Pb, Cr, Fe, Cu, Zn, Se, Hg, and As) were investigated in blood and feathers of 65 chicks from breeding colonies (Seomando, Hongdo, and Dokdo islet) of South Korea in 2010. Heavy metals were assayed by PerkinElmer NexION 300 inductively coupled plasma mass spectrometry. The mean concentrations of non-essential heavy metals were found to blood containing Cd (0.002 ~ 0.02 ppm), Pb (0.06 ~ 0.18) ppm, Hg (0.03 ~ 0.05) ppm, and As (0.26 ~ 0.48 ppm), and feather containing Cd (0.05 ~ 0.30 ppm), Pb (2.47 ~ 10.80 ppm), Hg (1.18 ~ 1.57 ppm), and As (0.15 ~ 0.44 ppm). Chicks on Seomando islet showed the highest levels of metals (Cd, Pb, Mn, Cr, Cu, and Se in blood; Al, As, Mn, Cr, Fe, Cu, and Se in feathers) among the colonies. Concentrations of Pb and Hg in feathers were the highest on Hongdo, and the levels of Cd and Zn in feathers were the highest on Dokdo islet. MT mRNA in the blood of Black-tailed gulls was relatively higher in gulls from Seomando than in gulls from Hongdo and Dokdo islet. MT mRNA level is thus positively correlated to heavy metal concentrations in Black-tailed gulls.


CIDNP study of the aromatic side chain interactions in myotoxin alpha.
CIDNP and COSY measurements were applied to study aromatic side chain interactions and conformations in myotoxin alpha, a Crotalus venom toxin which acts as blocker of the Ca2+ influx in the sarcoplasmic reticulum calcium pump. New evidence for the existence of a hydrophobic aromatic cluster at the amino terminus was obtained. This cluster consists of Tyr1, His5, His10, and (possibly) F12. The CIDNP data clearly establish that the usual order of the tyrosine 2, 6 and 3, 5 proton signals of Tyr1 is inverted, because of the large diamagnetic shielding effects of one ring on the other. The lines of the 2, 6 ring protons of Tyr1 and proton 4 in each of His5 and His10 are significantly broadened, an outcome of the side-chain hydrophobic interaction. The aromatic cluster could possibly present a hydrophobic sticky patch for binding of toxin by Ca2+ ATPase.


Predictive value of ANCA in atypical primary brain localization of Wegener's granulomatosis.
Wegener's Granulomatosis is a necrotizing vasculitis generally involving upper and lower respiratory tract and kidneys. The central nervous system is involved in less than 10% of the patients during the course of the disease and primary involvement is even rarer. We present and discuss the case of a patient with primitive cerebral localization of Wegener's Granulomatosis in which the diagnosis and the beginning of correct therapy were delayed, in spite of a rising c-ANCA titer, due to a misinterpretation of a bioptic specimen. This delay caused renal damage and pulmonary cavitations which needed a long time to recover. This case report suggests that the central nervous system can be the site of a primary localization of Wegener's Granulomatosis even without any other organ involvement. The diagnosis must be made as soon as possible in order to prevent spread to other sites since the disease is usually very aggressive and severe.


PANDA: a pipeline toolbox for analyzing brain diffusion images.
Diffusion magnetic resonance imaging (dMRI) is widely used in both scientific research and clinical practice in in-vivo studies of the human brain. While a number of post-processing packages have been developed, fully automated processing of dMRI datasets remains challenging. Here, we developed a MATLAB toolbox named "Pipeline for Analyzing braiN Diffusion imAges" (PANDA) for fully automated processing of brain diffusion images. The processing modules of a few established packages, including FMRIB Software Library (FSL), Pipeline System for Octave and Matlab (PSOM), Diffusion Toolkit and MRIcron, were employed in PANDA. Using any number of raw dMRI datasets from different subjects, in either DICOM or NIfTI format, PANDA can automatically perform a series of steps to process DICOM/NIfTI to diffusion metrics [e.g., fractional anisotropy (FA) and mean diffusivity (MD)] that are ready for statistical analysis at the voxel-level, the atlas-level and the Tract-Based Spatial Statistics (TBSS)-level and can finish the construction of anatomical brain networks for all subjects. In particular, PANDA can process different subjects in parallel, using multiple cores either in a single computer or in a distributed computing environment, thus greatly reducing the time cost when dealing with a large number of datasets. In addition, PANDA has a friendly graphical user interface (GUI), allowing the user to be interactive and to adjust the input/output settings, as well as the processing parameters. As an open-source package, PANDA is freely available at http://www.nitrc.org/projects/panda/. This novel toolbox is expected to substantially simplify the image processing of dMRI datasets and facilitate human structural connectome studies.


Identification of a specific receptor for interstitial collagenase on osteoblastic cells.
We have previously shown that the rat osteoblastic cell line UMR 106-01 responds to parathyroid hormone treatment by secreting interstitial collagenase. Secreted collagenase reaches a maximal concentration 12-24 h after parathyroid hormone stimulation, but then declines to undetectable levels by 96 h. Neither spontaneous nor cell-mediated extracellular degradation could account for this disappearance, since the enzyme maintained stability in both fresh and conditioned media. Instead, a cell-mediated binding mechanism was suggested by the rapid and saturable removal of exogenous purified rat collagenase at 37 degrees C. Binding studies using 125I-collagenase at 4 degrees C indicated a saturable receptor of a single class and 12,000 receptors per cell (Kd = 5 x 10(-9) M). A time course revealed specific receptor-mediated binding within 10 min and equilibrium by 60 min, while dissociation experiments further demonstrated reversibility. The kinetics of 125I-collagenase binding are characterized by the association (k1 = 4 x 10(6) M-1 min-1) and dissociation (k-1 = 2 x 10(-3) min-1) rate constants. The receptor was shown to be specific for rat collagenase since a host of related and unrelated proteins failed to compete for binding. Internalization studies revealed maximal intracellular accumulation at 30 min and complete degradation by 90 min, suggesting this receptor functions in these osteoblastic cells to eliminate extracellular collagenase.


[Analysis of Time-to-onset of Interstitial Lung Disease after the Administration of Small Molecule Molecularly-targeted Drugs].
The aim of this study was to investigate the time-to-onset of drug-induced interstitial lung disease (DILD) following the administration of small molecule molecularly-targeted drugs via the use of the spontaneous adverse reaction reporting system of the Japanese Adverse Drug Event Report database. DILD datasets for afatinib, alectinib, bortezomib, crizotinib, dasatinib, erlotinib, everolimus, gefitinib, imatinib, lapatinib, nilotinib, osimertinib, sorafenib, sunitinib, temsirolimus, and tofacitinib were used to calculate the median onset times of DILD and the Weibull distribution parameters, and to perform the hierarchical cluster analysis. The median onset times of DILD for afatinib, bortezomib, crizotinib, erlotinib, gefitinib, and nilotinib were within one month. The median onset times of DILD for dasatinib, everolimus, lapatinib, osimertinib, and temsirolimus ranged from 1 to 2 months. The median onset times of the DILD for alectinib, imatinib, and tofacitinib ranged from 2 to 3 months. The median onset times of the DILD for sunitinib and sorafenib ranged from 8 to 9 months. Weibull distributions for these drugs when using the cluster analysis showed that there were 4 clusters. Cluster 1 described a subgroup with early to later onset DILD and early failure type profiles or a random failure type profile. Cluster 2 exhibited early failure type profiles or a random failure type profile with early onset DILD. Cluster 3 exhibited a random failure type profile or wear out failure type profiles with later onset DILD. Cluster 4 exhibited an early failure type profile or a random failure type profile with the latest onset DILD.


Alterations in serum opsonic activity and complement levels in pneumococcal disease.
Pneumococcal opsonic activity and concentrations of pneumococcal capsular polysaccharide antigen, C3, C4 factor B, C3 and factor B breakdown products were measured in the serum obtained acutely from 12 patients with serious pneumococcal disease. One patient showed markedly reduced pneumococcal opsonic activity, borderline-low C3, and the presence of C3 and factor B breakdown products and died. Although eight additional patients showed depressed levels of C3 or C4 or the presence of C3 or factor B breakdown products, none had reduced pneumococcal opsonic activity. All of the three remaining patients had normal opsonic activity and C3 and C4 levels. Covalescent serum was obtained from eight patients; six had normal C3 and C4 levels, and two had persistent C4 depression. These data show that complement is activated during pneumococcal disease and suggest that extensive complement activation may impair pneumococcal opsonic activity in certain patients and thereby compromise an important host defense mechanism.


Complexes of RecA with LexA and RecX differentiate between active and inactive RecA nucleoprotein filaments.
The bacterial RecA protein has been the dominant model system for understanding homologous genetic recombination. Although a crystal structure of RecA was solved ten years ago, we still do not have a detailed understanding of how the helical filament formed by RecA on DNA catalyzes the recognition of homology and the exchange of strands between two DNA molecules. Recent structural and spectroscopic studies have suggested that subunits in the helical filament formed in the RecA crystal are rotated when compared to the active RecA-ATP-DNA filament. We examine RecA-DNA-ATP filaments complexed with LexA and RecX to shed more light on the active RecA filament. The LexA repressor and RecX, an inhibitor of RecA, both bind within the deep helical groove of the RecA filament. Residues on RecA that interact with LexA cannot be explained by the crystal filament, but can be properly positioned in an existing model for the active filament. We show that the strand exchange activity of RecA, which can be inhibited when RecX is present at very low stoichiometry, is due to RecX forming a block across the deep helical groove of the RecA filament, where strand exchange occurs. It has previously been shown that changes in the nucleotide bound to RecA are associated with large motions of RecA's C-terminal domain. Since RecX binds from the C-terminal domain of one subunit to the nucleotide-binding core of another subunit, a stabilization of RecA's C-terminal domain by RecX can likely explain the inhibition of RecA's ATPase activity by RecX.


Effects of Moderate- and High-Intensity Chronic Exercise on the Adiponectin Levels in Slow-Twitch and Fast-Twitch Muscles in Rats.
Background and objectives: Adipose tissue and skeletal muscle secrete adiponectin, a hormone abundantly secreted by adipocytes, that through the adiponectin receptor, regulate glucose and lipid metabolism. Adiponectin appears to protect skeletal muscles from inflammatory damage induced by oxidative stress. It has been suggested that decreased adiponectin levels could be associated with pathologic conditions, including obesity and diabetes. Furthermore, some studies suggest that exercise could have a beneficial effect by increasing adiponectin levels, but this observation remains controversial. It is also unknown if physical exercise modifies adiponectin expression in skeletal muscles. The aim of this study was to investigate the effect of chronic exercise on serum adiponectin and adiponectin expression in slow-twitch (soleus) and fast-twitch (plantaris) muscles in healthy rats. Materials and methods: Two-month-old male Wistar rats were randomly divided into three groups with n = 6 in each group: control (C), moderate-intensity training (MIT), and high-intensity training (HIT). The rats were conditioned to run on a treadmill for the 8-week period. Forty-eight hours after the last session, blood samples were collected for adiponectin measurements and total RNA was isolated from plantaris and soleus muscles to measure by RT-qPCR adiponectin receptor 1 and adiponectin mRNA expression level. Results: MIT and HIT groups had reduced adiponectin protein levels in serum and the plantaris muscle, but not changes in adiponectin protein were observed in the soleus muscle. No significant differences in Adiponectin receptor 1 (AdipoR1) gene expression were observed following intense or moderate exercise in either muscle group studied. Conclusions: Our study shows that decreasing levels of circulating adiponectin is a result of physical exercise and should not be generalized as a predictive marker of disease.


Chaotic physical security strategy based on manifold learning-assisted GANs for SDM-OFDM-PONs.
In this paper, we propose a high-security spatial division multiplexing orthogonal frequency division multiplexing passive optical network (SDM-OFDM-PON) encryption scheme based on manifold learning-assisted generative adversarial networks (MFGANs). The chaotic sequences generated by MFGANs are applied to produce the masking vectors to encrypt the constellation and frequency. With the help of manifold learning, the proposed scheme can learn the complex structures from various chaotic models and makes use of more parameters than a single traditional model to achieve the large key space of 1 × 10183. A 70 Gb/s encrypted OFDM signal transmission over 2 km 7-core fiber was experimentally demonstrated. In addition, due to the capacity of parallel computing of graphics processing units (GPUs), the encryption time by the proposed scheme is around 1.38% of the conventional encryption scheme. It is therefore shown that the proposed encryption scheme can ensure both efficiency and security in SDM-OFDM-PON systems.


Nurse describes caring for Manchester bomb victims.
A senior surgical ward sister has spoken of the emotional night shift caring for those injured in the Manchester Arena attack.


[Control of growth hormone synthesis, paradigm of tissue specificity and of hormonal gene expression regulation].
The study of the transcriptional control of the growth hormone gene illustrates the complementary role of three types of regulatory proteins. These proteins bind to the gene upstream of the transcription initiation site to stimulate or inhibit transcription. A first type of proteins includes ubiquitous factors. A second type includes receptors for hormones that act in the nucleus. A third type is represented by the pituitary factor Pit-1, the prototype of a novel class of proteins that are also involved in controlling embryonic development and cell proliferation. Indeed, Pit-1 determines not only the tissue specificity of expression of the growth hormone gene, but also its control by somatocrinin, as well as the ontogeny of the anterior pituitary and the maintenance of the differentiated phenotype.


Hearing Preservation in Patients Who Undergo Labyrinthectomy and Translabyrinthine Procedures: A Case Report and Systematic Review.
Preservation of endolymphatic fluids, maintenance of a fluid-filled vestibule, and preservation of the cochlear nerve and its vasculature are believed to be necessary to retaining hearing after an inner-ear operation. However, some studies have reported no hearing loss despite the violation of the vestibule, questioning the importance of maintaining a fluid-filled vestibule in preserving hearing. To report on the preservation of hearing after a complete labyrinthectomy for Meniere disease and after disruption of the vestibule. This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. A search of PubMed, Scopus, Ovid, and Cochrane Library databases was conducted to identify English-language articles on hearing preservation after labyrinthectomy, published from 1947 through December 11, 2019. The search strategy used a combination of boolean operators and included the following Medical Subject Heading terms and keywords: hearing preservation, labyrinth surgery, labyrinthectomy, vestibule violation, vestibule disruption, translabyrinthine approach, schwannoma removal, and semicircular canal ablation. Studies that included disruption of the vestibule and hearing preservation were included. This systematic review identified 10 studies with 10 patients who underwent surgical removal of cholesteatoma or vestibular schwannoma and displayed postoperative hearing preservation. This study also reported on 1 patient with Meniere disease who retained hearing after undergoing a complete labyrinthectomy. Among these 11 patients, the mean (range) age was 45.1 (27-55) years, and 8 patients (73%) were women. Multiple theories exist that explain the mechanism behind hearing preservation, such as sealing of the ductus reuniens or closure of the remaining vestibule. This systematic review describes a set of patients who did not experience hearing loss after a labyrinthectomy or surgical violation of the vestibule, which seems to contradict prevailing principles for retaining hearing after inner-ear surgical procedures. This finding suggests that hearing preservation is possible after labyrinthine destruction despite the absence of a fluid-filled vestibule and that other mechanisms, such as occlusion of the ductus reuniens with granulation tissue or bone dust, may be sufficient to achieve that outcome.


Electronic Energy Transfer in a Subphthalocyanine-Zn Porphyrin Dimer Studied by Linear and Nonlinear Ultrafast Spectroscopy.
The efficient harvesting and transport of visible light by electronic energy transfer (EET) are critical to solar energy conversion in both nature and molecular electronics. In this work, we study EET in a synthetic dyad comprising a visible absorbing subphthalocyanine (SubPc) donor and a Zn tetraphenyl porphyrin (ZnTPP) acceptor. Energy transfer is probed by steady-state spectroscopy, ultrafast transient absorption, and two-dimensional electronic spectroscopy. Steady-state and time-resolved experiments point to only weak electronic coupling between the components of the dimer. The weak coupling supports energy transfer from the SubPc to the zinc porphyrin in 7 ps, which itself subsequently undergoes intersystem crossing to populate the triplet state. The rate of the forward energy transfer is discussed in terms of the structure of the dimer, which is calculated by density functional theory. There is evidence of back energy transfer from the ZnTPP on the hundreds of picoseconds time scale. Sub-picosecond spectral diffusion was also observed and characterized, but it does not influence the picosecond energy transfer.