[An unusual form of macrodactylia].
The authors report a rare case of macrodactyly of the thumb in a 36 year old woman. The hypertrophy predominates on the epiphyseal tissue with complete ankylosis of the trapezo-metacarpal metacarpo-phalangeal, and interphalangeal joints in an abnormal position. This results in total functional incapacity of the thumb. The cosmetic and psychological impact are important to consider. Treatment consisted of two operative procedures. First a silastic implant for the trapezo-metacarpal joint and an arthrodesis of the metacarpophalangeal joint in a normal position was done. Three months later, the volume of the thumb was reduced by a longitudinal bone resection. The functional and cosmetic result is assessed. The literature is reviewed and the different modes of treatment utilized in such a malformation are presented. A relation between macrodactyly and lipomatous macrodystrophy is considered.


Nanotechnology for cancer treatment.
Nanotechnology has the potential to increase the selectivity and potency of chemical, physical, and biological approaches for eliciting cancer cell death while minimizing collateral toxicity to nonmalignant cells. Materials on the nanoscale are increasingly being targeted to cancer cells with great specificity through both active and passive targeting. In this review, we summarize recent literature that has broken new ground in the use of nanotechnology for cancer treatment with an emphasis on targeted drug delivery.


Highly isoselective ring-opening polymerization of rac-O-carboxyanhydrides using a zinc alkoxide initiator.
The stereoselective ring-opening polymerization (ROP) of O-carboxyanhydrides (OCAs) remains a major challenge due to the easy epimerization of monomers. In this work, using a zinc alkoxide initiator, highly efficient ROP of enantiopure 5-methyl-1,3-dioxolane-2,4-dione (LacOCA), 5-benzyl-1,3-dioxolane-2,4-dione (PheOCA), and 5-(4-(benzyloxy)benzyl)-1,3-dioxolane-2,4-dione (Try(Bn)OCA) was achieved without obvious epimerization. Moreover, highly isoselective ROP of rac-LacOCA, rac-PheOCA, and rac-Try(Bn)OCA was successful with the highest isoselectivity of Pm = 0.97 at -70 °C.


Equine seroprevalence rates as an additional indicator for a more accurate risk assessment of the West Nile virus transmission.
The West Nile Virus (WNV) is a zoonotic arbovirus that has recently been causing outbreaks in many countries in southern and Central Europe. In 2012, for the first time, it caused an outbreak in eastern Croatia with total of 7 human clinical cases. With an aim of assisting public health personnel in order to improve survey protocols and vector control, the high risk areas of the WNV transmission were estimated and mapped. The study area included cities of Osijek and Slavonski Brod and 8 municipalities in Vukovarsko-Srijemska County. Risk estimation was based on seroprevalence of WNV infections in horses as an indicator of the virus presence, as well as the presence of possible WNV mosquito vectors with corresponding vector competences. Four mosquito species considered as possible WNV vectors are included in this study: Aedes vexans, Culex modestus, Culex pipiens and Ochlerotatus caspius. Mosquitoes were sampled using dry-ice baited CDC trap, twice a month, between May and October. This study suggests that the two mosquito species present the main risk of WNV transmission in eastern Croatia: the Culex pipiens--because of good vector competence and the Aedes vexans--because of the very high abundances. As a result, these two species should be focus of future mosquito surveillance and a vector control management.


Interactive effect of sevoflurane with isradipine or indomethacin on spontaneous contractile activity of isolated pregnant rat myometrium.
Volatile anesthetics, calcium antagonists and non-steroidal anti-inflammatory drugs inhibit contractile activity of myometrial smooth muscle. The aim of this study was to investigate the interactive effect of sevoflurane with isradipine or indomethacin on spontaneous contractile activity of myometrial strips isolated from pregnant rats. The myometrial strips were excised from rats (250-300 g) at 19-21 days of gestation and mounted in tissue baths for recording of isometric tension. Sevoflurane (0.5 to 3 MAC) inhibited the amplitude and frequency of spontaneous myometrial contractions in a concentration-dependent manner (P<0.05). Sevoflurane responses were repeated in the presence of isradipine (a dihydropyridine-type calcium channel blocker) and indomethacin (a non-selective cyclooxygenase (COX) inhibitor). Pretreatment with isradipine (10(-6) M) or indomethacin (10(-7) M), concentrations that themselves had no effect on spontaneous contractility, significantly increased the inhibitor responses to sevoflurane on amplitude and frequency of myometrial contractions, beginning at 1 MAC (P<0.05). Blockade of calcium channels in myometrial smooth muscle may increase the inhibitor effect of sevoflurane. Further work is needed to determine the cellular mechanism(s) of this interaction.


Cell motility as a chemotherapeutic target.
The major cause of failure in the treatment of patients with solid malignancies is failure to prevent or control the spread of metastases. The metastatic process is a series of interrelated steps that must be accomplished before distant tumour foci can be established. Tumour cell motility is a complex process, which is involved in many of these steps. The mechanisms by which motility is stimulated and physically generated are complex and as yet poorly understood. Viewing the cell as a chemomechanical engine that relies on a tension based system for movement allows us to design chemotherapeutic strategies to inhibit tumour cell motility directly. Chemotherapeutic agents that block stimulation, interfere with cell-ECM interactions and interfere with cytoskeletal mechanics are already being tested. Further studies will be needed to define their efficacy.


Osteogenic lineage restriction by osteoprogenitors cultured on nanometric grooved surfaces: the role of focal adhesion maturation.
The differentiation of progenitor cells is dependent on more than biochemical signalling. Topographical cues in natural bone extracellular matrix guide cellular differentiation through the formation of focal adhesions, contact guidance, cytoskeletal rearrangement and ultimately gene expression. Osteoarthritis and a number of bone disorders present as growing challenges for our society. Hence, there is a need for next generation implantable devices to substitute for, or guide, bone repair in vivo. Cellular responses to nanometric topographical cues need to be better understood in vitro in order to ensure the effective and efficient integration and performance of these orthopedic devices. In this study, the FDA-approved plastic polycaprolactone was embossed with nanometric grooves and the response of primary and immortalized osteoprogenitor cells observed. Nanometric groove dimensions were 240 nm or 540 nm deep and 12.5 μm wide. Cells cultured on test surfaces followed contact guidance along the length of groove edges, elongated along their major axis and showed nuclear distortion; they formed more focal complexes and lower proportions of mature adhesions relative to planar controls. Down-regulation of the osteoblast marker genes RUNX2 and BMPR2 in primary and immortalized cells was observed on grooved substrates. Down-regulation appeared to directly correlate with focal adhesion maturation, indicating the involvement of ERK 1/2 negative feedback pathways following integrin-mediated FAK activation.


Role of chemokine receptors in thyroid cancer and immunotherapy.
Inflammation is currently regarded as an essential component of malignancies. It is now known that the tumor microenvironment may profoundly influence the biological behavior of cancer cells and ultimately the patient's outcome. Chemokine and their receptor play a major role in determining the immune phenotype of the cells infiltrating the thyroid tumor microenvironment. Experimental evidence shows that both normal and cancer thyroid cells express specific chemokine receptors. The expression of at least some of these receptors exerts several biological effects, which influence the course of the disease. The present review article will take into account the role of the most studied chemokine receptors (CXCR1, CXCR2, CXCR3, CXCR4, CXCR7, DARC, CCR3, CCR6 and CCR7) in the context of thyroid cancer. This review will focus on current knowledge provided by in vitro and in vivo studies specifically performed on thyroid cancer including (i) expression of chemokine receptors in normal and cancer thyroid cells; (ii) role of chemokine receptors in affecting the biological behavior of thyroid tumors including the metastatic process; (iii) current knowledge about immunotherapies through targeting of chemokine receptors in thyroid cancer.


[Demonstration of the effective of acupuncture on the autonomic nervous system by examination of the microcirculation].
This study served to compare the effect of needling at true acupuncture points with that of needling at non-acupuncture points. Various parameters were used to quantify the results such as measurement of the peripheral blood circulation in finger tips and the nasal mucous membrane, measurement of the skin temperature at various sites of the body by means of infrared thermography or contact thermometry, testing of skin conductance, or recording of heart frequency and respiration. These are all indicators of the functional state of the autonomic nervous system. This model experiment was performed on healthy volunteers and showed identical, transient, quick reflex responses of the sympathetic nervous system after true acupuncture as well as after needling at non-acupuncture points. These reactions are related to pain and do not allow to draw any conclusions on the specificity of the points that were needled. The aim of this project was not to make a statement about the therapeutic efficacy of acupuncture. It was meant to be a model allowing the study of some basic regulatory mechanisms which are fundamental for most treatments in complementary medicine.


Multivariate modeling of metabolic state vulnerabilities across diverse cancer contexts reveals synthetically lethal associations.
Targeting the distinct metabolic needs of tumor cells has recently emerged as a promising strategy for cancer therapy. The heterogeneous, context-dependent nature of cancer cell metabolism, however, poses challenges in identifying effective therapeutic interventions. Here, we utilize various unsupervised and supervised multivariate modeling approaches to systematically pinpoint recurrent metabolic states within hundreds of cancer cell lines, elucidate their association with tissue lineage and growth environments, and uncover vulnerabilities linked to their metabolic states across diverse genetic and tissue contexts. We validate key findings using data from an independent set of cell lines, pharmacological screens, and via single-cell analysis of patient-derived tumors. Our analysis uncovers new synthetically lethal associations between the tumor metabolic state (e.g., oxidative phosphorylation), driver mutations (e.g., loss of tumor suppressor PTEN), and actionable biological targets (e.g., mitochondrial electron transport chain). Investigating these relationships could inform the development of more precise and context-specific, metabolism-targeted cancer therapies.


Electrospray ionization mass spectrometry analysis of lysophospholipids in human ascitic fluids: comparison of the lysophospholipid contents in malignant vs nonmalignant ascitic fluids.
Lysophospholipids (lyso-PLs), including various glycerol-based and sphingosine-based lysophospholipids, play important roles in many biochemical, physiological, and pathological processes. The classical methods to analyze these lipids involve gas chromatography and/or high-performance liquid chromatography, which are time-consuming, cumbersome, and sometimes inaccurate due to the incomplete separation of closely related lipid species. We now describe the quantitative analysis of lyso-PLs in ascites samples from patients with ovarian cancer using electrospray ionization spectrometry. Three new classes of lyso-PL molecules are detected: alkyl-LPA, alkenyl-LPA, and methylated lysophosphatidylethanolamine. Importantly, the following lysophospholipid species are significantly increased in ascites from patients with ovarian cancer, compared to patients with nonmalignant diseases (e.g., liver failure): LPA (including acyl-, alkyl-, and alkenyl-LPA species), lysophosphatidylinositol, and sphingosylphosphorylcholine. Lysophosphorylcholine contents are also significantly different among ascitic fluids from the two groups of patients. However, the total phosphate content in ascites samples from patients with ovarian cancer is not significantly different compared to that from patients with nonmalignant disease.


Molecular Memories of a Cambrian Fossil.
Evolutionary evidence is important scientific background for appreciating the theory of evolution. We describe a STEAM-based lesson plan that uses paleontological drawings and a modern evolutionary database to explore and understand fossil, morphological, and molecular evidence. Together, with a focus on arthropods and the Cambrian explosion, students experience a heuristic process common in scientific reasoning, guiding them toward practices that synthesize knowledge and invite questioning in the life sciences.


Bactericidal Ability of Well-Controlled Cationic Polymer Brush Surfaces and the Interaction Analysis by Quartz Crystal Microbalance with Dissipation.
In this study, cationic poly(2-(methacryloyloxy)ethyl) trimethylammonium chloride) (PMTAC) brush surfaces were prepared by surface-initiated atom transfer radical polymerization (SI-ATRP), and their properties were systematically investigated to discuss the factors affecting their bactericidal properties and interactions with proteins. Model equations for the analysis of electrophoretic behaviors were considered for accurate parameter estimation to indicate the charge density at the interface. The zeta potential dependency of the PMTAC brushes was successfully analyzed using Smolchowski's equation and the Gouy-Chapman model, which describes the diffusive electric double layer. The analysis of the quartz crystal microbalance with dissipation (QCM-D) indicated that the electrostatic interaction promoted protein adsorption, with a large quantity of a negatively charged protein, bovine serum albumin (BSA), being adsorbed. The bactericidal efficiency of the high-graft-density polymer brush (0.45 chains nm-2) was higher than that of the low-graft-density polymer brush (0.06 chains nm-2). To investigate the mechanism of this phenomenon, we applied the dissipation change (ΔD) of QCM-D analysis. The BSA was likewise adsorbed when the brush structure was changed; however, the negative ΔD indicated that the BSA-adsorbed, high-graft-density PMTAC brush became a rigid state. In the bacteria culture media, the behaviors were the same as BSA adsorption, and the high-graft-density polymer brush was also estimated to be more rigid than the low-graft-density polymer brush. Moreover, for S. aureus adhesion after incubating in TSB, a small slope of ΔD/ΔF plots considered initial adsorption of bacteria on the high-graft-density polymer brush strongly interacted compared to that of the low-graft-density polymer brush. The scattered value of the slope of ΔD/ΔF on the high-graft-density polymer brush was considered to be due to the dead bacteria between the bacteria and the polymer brush interface. These investigations for a well-defined cationic polymer brush will contribute to the design of antibacterial surfaces.


Understanding Early-Life Adaptive Immunity to Guide Interventions for Pediatric Health.
Infants are capable of mounting adaptive immune responses, but their ability to develop long-lasting immunity is limited. Understanding the particularities of the neonatal adaptive immune system is therefore critical to guide the design of immune-based interventions, including vaccines, in early life. In this review, we present a thorough summary of T cell, B cell, and humoral immunity in early life and discuss infant adaptive immune responses to pathogens and vaccines. We focus on the differences between T and B cell responses in early life and adulthood, which hinder the generation of long-lasting adaptive immune responses in infancy. We discuss how knowledge of early life adaptive immunity can be applied when developing vaccine strategies for this unique period of immune development. In particular, we emphasize the use of novel vaccine adjuvants and optimization of infant vaccine schedules. We also propose integrating maternal and infant immunization strategies to ensure optimal neonatal protection through passive maternal antibody transfer while avoiding hindering infant vaccine responses. Our review highlights that the infant adaptive immune system is functionally distinct and uniquely regulated compared to later life and that these particularities should be considered when designing interventions to promote pediatric health.


Height, adiposity and body fat distribution and breast density in young women.
Breast density is one of the strongest risk factors for breast cancer, but determinants of breast density in young women remain largely unknown. Associations of height, adiposity and body fat distribution with percentage dense breast volume (%DBV) and absolute dense breast volume (ADBV) were evaluated in a cross-sectional study of 174 healthy women, 25 to 29 years old. Adiposity and body fat distribution were measured by anthropometry and dual-energy X-ray absorptiometry (DXA), while %DBV and ADBV were measured by magnetic resonance imaging. Associations were evaluated using linear mixed-effects models. All tests of statistical significance are two-sided. Height was significantly positively associated with %DBV but not ADBV; for each standard deviation (SD) increase in height, %DBV increased by 18.7% in adjusted models. In contrast, all measures of adiposity and body fat distribution were significantly inversely associated with %DBV; a SD increase in body mass index (BMI), percentage fat mass, waist circumference and the android:gynoid fat mass ratio (A:G ratio) was each associated significantly with a 44.4 to 47.0% decrease in %DBV after adjustment for childhood BMI and other covariates. Although associations were weaker than for %DBV, all measures of adiposity and body fat distribution also were significantly inversely associated with ADBV before adjustment for childhood BMI. After adjustment for childhood BMI, however, only the DXA measures of percentage fat mass and A:G ratio remained significant; a SD increase in each was associated with a 13.8 to 19.6% decrease in ADBV. In mutually adjusted analysis, the percentage fat mass and the A:G ratio remained significantly inversely associated with %DBV, but only the A:G ratio was significantly associated with ADBV; a SD increase in the A:G ratio was associated with an 18.5% decrease in ADBV. Total adiposity and body fat distribution are independently inversely associated with %DBV, whereas in mutually adjusted analysis only body fat distribution (A:G ratio) remained significantly inversely associated with ADBV in young women. Research is needed to identify biological mechanisms underlying these associations.


Prognostic Factors for Large Symptomatic Gists: a Pragmatic Study of Experiences From a University Hospital Over 10 Years
Background: Gastrointestinal stromal tumors (GISTs), which are mesenchymal neoplasms in the gastrointestinal (GI) tract account for 0.2% of all GI tumors. Several factors have been reported (mostly from studies conducted in Western countries) to be associated with survival in GISTs cases such as tumor site, staging, and tumor size. We conducted a pragmatic study, looking at a 10-year period, aimed at understanding the prognostic factors related to GISTs in a university hospital. The study population consisted of patients with large symptomatic GISTs. Methods: This was a retrospective study conducted at the Department of Surgery in the Khon Kaen University Hospital (Thailand). All patients diagnosed with GISTs that were treated between 2006 and 2015 were consecutively enrolled. The diagnosis of GISTs was made by examining the pathological section and immunohistochemistry results. The outcome of this study was the rate of survival after surgical treatment. Prognostic factors were determined using Cox regression analysis. Results: There were 124 GISTs patients treated at the university hospital during the 10-year period of the study. The median age of all patients was 54 years (range 24-83 years). Of those, 119 (95.9%) were symptomatic. Rectosigmoid GISTs accounted for 20.2% of all tumors. The median tumor size was 8 cm. A total of 68 patients (54.8%) died. The median survival time for all patients was 7.18 years (1st -3rd quartile range 6.48-7.89). There were three significant factors associated with death including male gender, liver metastasis, and peritoneal metastasis. Conclusion: Male gender, liver metastasis, and peritoneal metastasis were prognostic factors for large symptomatic GISTs.


Relief of chronic pain associated with increase in midline frontal theta power.
There is a need to identify objective cortical electrophysiological correlates for pain relief that could potentially contribute to a better pain management. However, the field of developing brain biomarkers for pain relief is still largely underexplored. The objective of this study was to investigate cortical electrophysiological correlates associated with relief from chronic pain. Those features of pain relief could serve as potential targets for novel therapeutic interventions to treat pain. In 12 patients with chronic pain in the upper or lower extremity undergoing a clinically indicated nerve block procedure, brain activity was recorded by means of electroencephalogram before and 30 minutes after the nerve block procedure. To determine the specific cortical electrophysiological correlates of relief from chronic pain, 12 healthy participants undergoing cold-pressor test to induce experimental acute pain were used as a control group. The data were analyzed to characterize power spectral density patterns of pain relief and identify their source generators at cortical level. Chronic pain relief was associated with significant delta, theta, and alpha power increase at the frontal area. However, only midfrontal theta power increase showed significant positive correlation with magnitude of reduction in pain intensity. The sources of theta power rebound were located in the left dorsolateral prefrontal cortex (DLPFC) and midline frontal cortex. Furthermore, theta power increase in the midline frontal cortex was significantly higher with chronic vs acute pain relief. These findings may provide basis for targeting chronic pain relief via modulation of the midline frontal theta oscillations.


Etiology of bloody diarrhea in Bolivian children: implications for empiric therapy. Bolivian Dysentery Study Group.
In Bolivia, few data are available to guide empiric therapy for bloody diarrhea. A study was conducted between December 1994 and April 1995 to identify organisms causing bloody diarrhea in Bolivian children. Rectal swabs from children <5 years old with bloody diarrhea were examined for Salmonella, Shigella, and Campylobacter organisms; fecal specimens were examined for Entamoeba histolytica. A bacterial pathogen was identified in specimens from 55 patients (41%). Shigella organisms were found in 39 specimens (29%); 37 isolates (95%) were resistant to ampicillin, 35 (90%) to trimethoprim-sulfamethoxazole, and 24 (62%) to chloramphenicol, but all were susceptible to nalidixic acid. Only 1 of 133 stool specimens contained E. histolytica trophozoites. Multidrug-resistant Shigella species are a frequent cause of bloody diarrhea in Bolivian children; E. histolytica is uncommon. Clinical predictors described in this study may help identify patients most likely to have Shigella infection. Laboratory surveillance is essential to monitor antimicrobial resistance and guide empiric treatment.


Liver allograft rejection in rats depleted of CD8+ cells.
The mechanism(s) of rejection or tolerance induction is a competitive, complex process that presumably involves interactions between multiple subpopulations of T lymphocytes. We investigated the roles of CD8+ cytolytic and CD4+ helper T cells in rat strains that tolerate liver allografts and that differ at both the major histocompatibility complex (MHC) (RT1) and minor histocompatibility genes. Orthotopic liver transplantation (OLT) with arterial reconstruction was performed with Brown Norway (BN) (RT1n) donors and Lewis (RT1(1)) recipients, some of which were untreated, others treated with anti-CD8 antibody, and still others treated with anti-CD4 antibody. Liver graft rejection was monitored for 28 days on the basis of two criteria: (1) serum levels of AST enzyme at 3-day intervals and (2) liver biopsies at weekly intervals and at the time of sacrifice at the end of the study period. In the untreated control group, an elevation of AST was found to peak at day 6 after grafting, and it remained elevated until day 28 (AST 542 +/- 72 U/l). Histologically, signs of severe rejection were first observed on day 9; these changed to moderate rejection about day 21 and to mild rejection by day 28, when the animals were sacrificed. Recipients pre-treated with anti-CD8 demonstrated a significant elevation of AST within 6 days that, unlike in the control recipients, continued to rise sharply through the observation period (AST 1127 +/- 181 U/l, P = 0.009 vs control group). Liver biopsies showed mild rejection at day 9 and moderate rejection at days 21 through 28. Recipients pretreated with anti-CD4 showed a time course of enzyme elevation and severity of rejection that was not significantly different from that observed in the control group. However, anti-CD4 treatment resulted in only 75% depletion of CD4+ cells in peripheral blood as compared to complete elimination of CD8+ cells following anti-CD8 treatment. Functional studies of spleen and liver-infiltrating lymphocytes obtained after 28 days showed low proliferative response in mixed lymphocyte culture with both BN and PVG stimulator spleen and lymph node cells. These results suggest that in this donor/recipient combination, removal of CD8+ cells increases the severity of rejection as demonstrated by a progressive rise in AST and histology. Moreover, OLT in this combination results in a profound, nonspecific inhibition of proliferative T-cell responses to MHC alloantigens.


Late-onset Sepsis in Preterm Infants Can Be Detected Preclinically by Fecal Volatile Organic Compound Analysis: A Prospective, Multicenter Cohort Study.
The intestinal microbiota has increasingly been considered to play a role in the etiology of late-onset sepsis (LOS). We hypothesize that early alterations in fecal volatile organic compounds (VOCs), reflecting intestinal microbiota composition and function, allow for discrimination between infants developing LOS and controls in a preclinical stage. In 9 neonatal intensive care units in the Netherlands and Belgium, fecal samples of preterm infants born at a gestational age ≤30 weeks were collected daily, up to the postnatal age of 28 days. Fecal VOC were measured by high-field asymmetric waveform ion mobility spectrometry (FAIMS). VOC profiles of LOS infants, up to 3 days prior to clinical LOS onset, were compared with profiles from matched controls. In total, 843 preterm born infants (gestational age ≤30 weeks) were included. From 127 LOS cases and 127 matched controls, fecal samples were analyzed by means of FAIMS. Fecal VOCs allowed for preclinical discrimination between LOS and control infants. Focusing on individual pathogens, fecal VOCs differed significantly between LOS cases and controls at all predefined time points. Highest accuracy rates were obtained for sepsis caused by Escherichia coli, followed by sepsis caused by Staphylococcus aureus and Staphylococcus epidermidis. Fecal VOC analysis allowed for preclinical discrimination between infants developing LOS and matched controls. Early detection of LOS may provide clinicians a window of opportunity for timely initiation of individualized therapeutic strategies aimed at prevention of sepsis, possibly improving LOS-related morbidity and mortality.


A conditional predictive p-value to compare a multinomial with an overdispersed multinomial in the analysis of T-cell populations.
Immunological experiments that record primary molecular sequences of T-cell receptors produce moderate to high-dimensional categorical data, some of which may be subject to extra-multinomial variation caused by technical constraints of cell-based assays. Motivated by such experiments in melanoma research, we develop a statistical procedure for testing the equality of two discrete populations, where one population delivers multinomial data and the other is subject to a specific form of overdispersion. The procedure computes a conditional-predictive p-value by splitting the data set into two, obtaining a predictive distribution for one piece given the other, and using the observed predictive ordinate to generate a p-value. The procedure has a simple interpretation, requires fewer modeling assumptions than would be required of a fully Bayesian analysis, and has reasonable operating characteristics as evidenced empirically and by asymptotic analysis.


Thermally Controlled Construction of Fe-Nx Active Sites on the Edge of a Graphene Nanoribbon for an Electrocatalytic Oxygen Reduction Reaction.
Pyrolytically prepared iron and nitrogen codoped carbon (Fe/N/C) catalysts are promising nonprecious metal electrocatalysts for the oxygen reduction reaction (ORR) in fuel cell applications. Fabrication of the Fe/N/C catalysts with Fe-Nx active sites having precise structures is now required. We developed a strategy for thermally controlled construction of the Fe-Nx structure in Fe/N/C catalysts by applying a bottom-up synthetic methodology based on a N-doped graphene nanoribbon (N-GNR). The preorganized aromatic rings within the precursors assist graphitization during generation of the N-GNR structure with iron-coordinating sites. The Fe/N/C catalyst prepared from the N-GNR precursor, iron ion, and the carbon support Vulcan XC-72R provides a high onset potential of 0.88 V (vs reversible hydrogen electrode (RHE)) and promotes efficient four-electron ORR. X-ray absorption fine structure (XAFS) and X-ray photoelectron spectroscopy (XPS) studies reveal that the N-GNR precursor induces the formation of iron-coordinating nitrogen species during pyrolysis. The details of the graphitization process of the precursor were further investigated by analyzing the precursors pyrolyzed at various temperatures using MgO particles as a sacrificial template, with the results indicating that the graphitized structure was obtained at 700 °C. The preorganized N-GNR precursors and its pyrolysis conditions for graphitization are found to be important factors for generation of the Fe-Nx active sites along with the N-GNR structure in high-performance Fe/N/C catalysts for the ORR.


[Preparation of molecularly imprinted polypyrrole/Fe3O4 composite material and its application in recognition of tryptophan enantiomers].
Ferrosoferric oxide (Fe(3)O(4)) magnetic material was first synthesized, and then the in-situ chemical polymerization of pyrrole was carried out on the surface of Fe(3)O(4) by using pyrole and L-tryptophan (L-Trp) as the functional monomer and templates, respectively. As a result, molecularly imprinted polypyrrole/Fe(3)O(4) composite material was obtained. This composite material was separated from the solution because of its magnetic property. Polypyrrole in the composite was overoxidized in 1 mol/L NaOH solution by applying a potential of 1.0 V, and thus L-Trp templates were de-deoped from the composite. Scanning electron microscopy (SEM), X-ray diffraction (XRD) and electrochemical methods were employed to characterize the composite. The solution containing L- or D-Trp was pumped through a porous ceramic tube packed with the composite, separately. High performance liquid chromatography (HPLC) was adopted for the detection of L- or D-Trp in the eluate, and the results indicated that the enrichment ability of the composite for L-Trp was almost 2 times that of D-Trp. Therefore, the electro-magnetic composite material has potential applications as chromatographic stationary phase for chiral recognition.


Modification of a hydrophobic layer by a point mutation in syntaxin 1A regulates the rate of synaptic vesicle fusion.
Both constitutive secretion and Ca(2+)-regulated exocytosis require the assembly of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complexes. At present, little is known about how the SNARE complexes mediating these two distinct pathways differ in structure. Using the Drosophila neuromuscular synapse as a model, we show that a mutation modifying a hydrophobic layer in syntaxin 1A regulates the rate of vesicle fusion. Syntaxin 1A molecules share a highly conserved threonine in the C-terminal +7 layer near the transmembrane domain. Mutation of this threonine to isoleucine results in a structural change that more closely resembles those found in syntaxins ascribed to the constitutive secretory pathway. Flies carrying the I254 mutant protein have increased levels of SNARE complexes and dramatically enhanced rate of both constitutive and evoked vesicle fusion. In contrast, overexpression of the T254 wild-type protein in neurons reduces vesicle fusion only in the I254 mutant background. These results are consistent with molecular dynamics simulations of the SNARE core complex, suggesting that T254 serves as an internal brake to dampen SNARE zippering and impede vesicle fusion, whereas I254 favors fusion by enhancing intermolecular interaction within the SNARE core complex.


Species review of the genus Boreophilia Benick from North America (Coleoptera, Staphylinidae, Aleocharinae, Athetini): Systematics, habitat, and distribution.
Fourteen species of the genus Boreophilia Benick are now recognized in North America. Boreophiliainsecuta (Eppelsheim), reported by Lohse (1990) from North America, is a misidentification of a new species, which is described here as B.neoinsecuta Klimaszewski, sp. n., and the true B.insecuta (Epp.) does not occur in North America. An additional new species is found in Alaska, and described as B.beringi Klimaszewski & Brunke, sp. n. The following three species are synonymized (second name being valid): Boreophiliaherschelensis Klimaszewski & Godin, 2012, with Boreophiliavega (Fenyes, 1920); Boreophiliamanitobensis Lohse, 1990, with B.caseyi Lohse, 1990; and B.angusticornis (Bernahuer, 1907) with B.subplana (J Sahlberg, 1880), based on study of genital structures and external morphology. Athetagelida J Sahlberg, 1887, and Athetamunsteri Bernhauer, 1902, considered as Boreophilia in recent publications, are transferred to the genus Atheta Thomson, subgenus Dimetrota. Boreostibapiligera (J Sahlberg) is transferred to Boreophilia based on morphology and the results of our phylogenetic analysis. Boreophilianearctica is recorded from Alberta and B.nomensis is recorded from British Columbia for the first time. Each valid species is illustrated by color image of habitus, and black and white images of genitalia and tergite and sternite VIII. A new key to all Nearctic species of the genus is provided. DNA barcode data were available for nine of the 14 species, which we downloaded, analyzed, and used as additional evidence for the taxonomic conclusions reached herein.


Platelet-to-Lymphocyte Ratio Predicts the Presence of Diabetic Neurogenic Bladder.
Diabetic neurogenic bladder (DNB) has been widely recognized in recent years. It is common in patients with long-term diabetes and may also lead to many severe complications. Although there has been widespread evidence that inflammation is involved in the development of some diabetic complications, there is little evidence that this can also occur in the bladder. In recent years, platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) have been viewed as potential novel markers of inflammatory responses. This study was designed to evaluate the relationship between the presence of DNB and the PLR and NLR. A total of 371 cases of T2DM patients were included in this retrospective study. Patients were divided into two groups, with 115 diabetic subjects diagnosed with diabetic neurogenic bladder and 256 control subjects without DNB. The independent predictors of DNB were analyzed using logistic regression. Compared with patients without DNB, the mean PLR and NLR were significantly higher in those with DNB (p < 0.001). Based on the logistic regression, PLR was found to be an independent risk factor for DNB (odds ratio [OR]: 1.408, 95% confidence interval [CI]: 1.248-1.617). From the receiver operating characteristic (ROC) curve, using PLR as indicative of DNB was expected to be 101.1949, and it generated a sensitivity and specificity value of 89.6% and 23.4%, respectively. The area under the curve (AUC) was also found to be 0.899 (95% CI: 0.865-0.932). In our study, PLR and NLR were significantly higher for patients with DNB. The PLR was found to be a risk factor in the presence of DNB after correcting for possible confounding factors. Considering the severe complications associated with DNB, patients with elevated PLR should be seriously cared for in clinics.


High performance thin-film composite forward osmosis membrane.
Recent studies show that osmotically driven membrane processes may be a viable technology for desalination, water and wastewater treatment, and power generation. However, the absence of a membrane designed for such processes is a significant obstacle hindering further advancements of this technology. This work presents the development of a high performance thin-film composite membrane for forward osmosis applications. The membrane consists of a selective polyamide active layer formed by interfacial polymerization on top of a polysulfone support layer fabricated by phase separation onto a thin (40 mum) polyester nonwoven fabric. By careful selection of the polysulfone casting solution (i.e., polymer concentration and solvent composition) and tailoring the casting process, we produced a support layer with a mix of finger-like and sponge-like morphologies that give significantly enhanced membrane performance. The structure and performance of the new thin-film composite forward osmosis membrane are compared with those of commercial membranes. Using a 1.5 M NaCl draw solution and a pure water feed, the fabricated membranes produced water fluxes exceeding 18 L m(2-)h(-1), while consistently maintaining observed salt rejection greater than 97%. The high water flux of the fabricated thin-film composite forward osmosis membranes was directly related to the thickness, porosity, tortuosity, and pore structure of the polysulfone support layer. Furthermore, membrane performance did not degrade after prolonged exposure to an ammonium bicarbonate draw solution.


Inclusive mosaic: promoting diversity in nursing through youth mentorship.
In this paper we describe the Inclusive Mosaic project, a community-university partnership in an outer-city community in a large Canadian metropolis aimed at promoting diversity in nursing. The project brought together nursing student mentors with middle school and high school youth from diverse backgrounds in a mentoring program aimed at increasing participants' interest in, and confidence in pursuing, higher education and a career in nursing or other health profession. The concepts of emancipatory education, self-efficacy, and possible selves provided the theoretical foundation. Project processes, activities, and outcomes are described, and a post-hoc evaluation encompassing the project's strengths, challenges, limitations, and successes is presented. Recommendations to inform future research and education are also provided.


[The treatment of cytomegalovirus retinitis in human immunodeficiency virus infection].
Most of the patients with immunodeficiency virus infection (75%-85%) are coinfected with cytomegalovirus. It is estimated that cytomegalovirus disease develops in 45% of them, mainly those presenting low CD4 cell counts (< 100/mm3). Retinitis is the most common manifestation of reactivated cytomegalovirus disease (85%), followed by other extra ocular sites (central nervous system, lungs, gastrointestinal system, adrenal glands, etc.). The particularly high incidence of cytomegalovirus retinitis, the difficulties concerning its therapeutical approach and the relatively unsatisfactory results, justify this review, according to the new treatment options presented in recent literature.


Sex-dependent effects of early life inflammatory pain on sucrose intake and sucrose-associated hippocampal Arc expression in adult rats.
We hypothesize that dorsal hippocampal (dHC) neurons, which are critical for episodic memory, form a memory of a meal and inhibit the initiation of the next meal and the amount ingested during that meal. In support, we showed previously that (1) consuming a sucrose meal induces expression of the synaptic plasticity marker activity-regulated cytoskeleton-associated protein (Arc) in dHC neurons and (2) reversible inactivation of these neurons immediately following a sucrose meal accelerates the onset of the next meal and increases the size of that meal. These data suggest that hippocampal-dependent memory inhibits intake; therefore, the following experiments were conducted to determine whether hippocampal-dependent memory impairments are associated with increased intake. We reported recently that one episode of early life inflammatory pain impairs dHC-dependent memory in adult rats. The present study determined whether neonatal inflammatory pain also increases sucrose intake and attenuates sucrose-associated Arc expression. Male and female Sprague-Dawley rats were given an intraplantar injection of the inflammatory agent carrageenan (1%) on the day of birth and sucrose intake and sucrose-associated dHC Arc expression were measured in adulthood. Neonatal inflammatory pain increased sucrose intake in adult female and male rats, decreased sucrose-associated dHC Arc expression in female rats, and tended to have a similar effect on Arc expression in male rats. Neonatal inflammatory pain significantly decreased the interval between two sucrose meals in female but not in male rats. Morphine administration at the time of insult attenuated the effects of injury on sucrose intake. Collectively, these findings indicate that one brief episode of inflammatory pain on the day of birth has a long long-lasting, sex-dependent impact on intake of a palatable food in adulthood.


Gonococci causing disseminated gonococcal infection are resistant to the bactericidal action of normal human sera.
The susceptibility of strains of Neisseria gonorrhoeae to the bactericidal action of normal human sera was determined for isolates from patients with disseminated gonococcal infection and uncomplicated gonorrhea. Serum susceptibility was correlated with penicillin susceptibility and auxotype. 38 of 39 strains (97%) of N. gonorrhoeae from Seattle patients with disseminated gonococcal infection were resistant to the complement-dependent bactericidal action of normal human sera. 36 of these were inhibited by less than or equal to mug/ml of penicillin G and required arginine, hypoxanthine, and uracil for growth on chemically defined medium (Arg-Hyx-Ura- auxotype). 12 of 43 isolates from patients with uncomplicated gonorrhea were also of the Arg-Hyx-Ura-auxotype, inhibited by less than or equal to 0.030 mug/ml of penicillin G, and serum resistant. Of the 31 remaining strains of other auxotypes isolated from patients with uncomplicated gonorrhea, 18 (58.1%) were sensitive to normal human sera in titers ranging from 2 to 2,048. The bactericidal action of normal human sera may prevent the dissemination of serum-sensitive gonococci. However, since only a small proportion of individuals infected by serum-resistant strains develop disseminated gonococcal infection, serum resistance appears to be a necessary but not a sufficient virulence factor for dissemination. Host factors such as menstruation and pharyngeal gonococcal infection may favor the dissemination of serum-resistant strains. Since serum-resistant Arg-Hyx-Ura strains are far more frequently isolated from patients with disseminated gonococcal infection than serum-resistant strains of other auxotypes, Arg-Hyx-Ura-strains may possess other virulence factors in addition to serum resistance.


[Effects of physical training on endocrine functions].
Muscular exercise has an impact on endocrine functions. A single bout of exercise (for example, running for 30 minutes) activates certain endocrine systems required to maintain body homeostasis. Moreover, the effects of exercise persist after the end of exercise, continuing during the recovery period. Training, i.e. regularly repeated exercise, can affect endocrine functions by modifying hormonal responses to exercise and/or by modifying endocrine functions in resting conditions. In other words, endocrine functions adapt to repeated muscular exercise. The understanding of such modifications should allow avoiding unwarranted hormonal substitution in sportsmen and sportswomen.


Secondary hormonal manipulation of prostate cancer.
Prostate cancer is the second leading cause of cancer mortality among men in Western countries. The initial treatment of advanced prostate cancer is suppression of testicular androgen production by medical or surgical castration, but nearly all men with metastases develop disease progression. Patients with hormone-resistant prostate cancer (HRPC) have a median survival of approximately 18 months, and no therapy has yet demonstrated a definitive survival advantage. However, in the past several years, a number of promising new treatment strategies have emerged. One of the most important new treatment strategies involves secondary hormonal manipulation after the failure of primary androgen deprivation. This approach is predicated on the recognition that HRPC is a heterogeneous disease, and some patients may respond to alternative hormonal interventions despite the presence of castrate levels of testosterone.


Varieties of stable vortical solitons in Ginzburg-Landau media with radially inhomogeneous losses.
Using a combination of the variation approximation and direct simulations, we consider the model of the light transmission in nonlinearly amplified bulk media, taking into account the localization of the gain, i.e., the linear loss shaped as a parabolic function of the transverse radius, with a minimum at the center. The balance of the transverse diffraction, self-focusing, gain, and the inhomogeneous loss provides for the hitherto elusive stabilization of vortex solitons, in a large zone of the parameter space. Adjacent to it, stability domains are found for several novel kinds of localized vortices, including spinning elliptically shaped ones, eccentric elliptic vortices which feature double rotation, spinning crescents, and breathing vortices.


Electronic medical records, nurse staffing, and nurse-sensitive patient outcomes: evidence from California hospitals, 1998-2007.
To estimate the effects of electronic medical records (EMR) implementation on medical-surgical acute unit costs, length of stay, nurse staffing levels, nursing skill mix, nurse cost per hour, and nurse-sensitive patient outcomes. Data on EMR implementation came from the 1998-2007 HIMSS Analytics Databases. Data on nurse staffing and patient outcomes came from the 1998-2007 Annual Financial Disclosure Reports and Patient Discharge Databases of the California Office of Statewide Health Planning and Development (OSHPD). Longitudinal analysis of an unbalanced panel of 326 short-term, general acute care hospitals in California. Marginal effects estimated using fixed effects (within-hospital) OLS regression. EMR implementation was associated with 6-10 percent higher cost per discharge in medical-surgical acute units. EMR stage 2 increased registered nurse hours per patient day by 15-26 percent and reduced licensed vocational nurse cost per hour by 2-4 percent. EMR stage 3 was associated with 3-4 percent lower rates of in-hospital mortality for conditions. Our results suggest that advanced EMR applications may increase hospital costs and nurse staffing levels, as well as increase complications and decrease mortality for some conditions. Contrary to expectation, we found no support for the proposition that EMR reduced length of stay or decreased the demand for nurses.


Recovery of Escherichia coli from chlorinated secondary sewage.
Escherichia coli ATCC 27622 injured during chlorination of secondary sewage failed to produce colonies on membrane filters incubated on m-FC medium or to grow and produce gas in lactose broth. Thus, standard methods for the enumeration of total and fecal coliforms in water and wastes should not be applied to chlorinated effluents.


Processing and secretion in the neurohypophysis. Stability of isolated secretory vesicles and role of internal pH.
A possible role of low pH in secretory vesicles for processing and secretion in the neurohypophysis was investigated. Subcellular fractionation of guinea-pig neural lobes revealed that a proton present in the membranes from this tissue could not be ascribed to secretory vesicles. However, a proton pump was found in coated microvesicles. Secretory vesicles isolated from rats and guinea pigs were stable under conditions known to lyse secretory vesicles from the adrenal medulla owing to the generation of a proton gradient. These results suggest that the internal pH of secretory vesicles from the neurohypophysis is closer to neutral than is the pH in chromaffin secretory vesicles. Processing of a neurophysin-glycopeptide intermediate from the biosynthesis of vasopressin in intact secretory vesicles incubated in vitro was activated by the addition of NH4Cl, known to increase the intravesicular pH. This activation of neurohormone processing was also apparent in isolated nerve endings incubated in the presence of NH4Cl, suggesting that NH4Cl can also be used to increase the intravesicular pH in intact nerve endings. However, NH4Cl did not affect the secretion of neurohormones, indicating that a low intravesicular pH is not important for exocytosis in the neurohypophysis. Our results indicate that a low pH generated during processing by mechanisms other than ATP-dependent proton transport may inhibit the processing enzymes, thereby preventing extensive breakdown of neurohormone precursors.


Very low affinity B cells form germinal centers, become memory B cells, and participate in secondary immune responses when higher affinity competition is reduced.
To understand the relationship between the affinity of the B cell antigen receptor (BCR) and the immune response to antigen, two lines of immunoglobulin H chain transgenic (Tg) mice were created. H50Gmu(a) and T1(V23)mu(a) mice express mu H chain transgenes that associate with the lambda1 L chains to bind the (4-hydroxy-3-nitrophenyl)acetyl hapten with association constants (K(a)s) of only 1.2 x 10(5) M(-1) and 3 x 10(4) M(-1), respectively. Both lines mounted substantial antibody-forming cell (AFC) and germinal center (GC) responses. H50Gmu(a) Tg mice also generated memory B cells. T1(V23)mu(a) B cells formed AFC and GCs, but were largely replaced in late GCs by antigen-specific cells that express endogenous BCRs. Thus, B lymphocytes carrying BCRs with affinities previously thought to be irrelevant in specific immune responses are in fact capable of complete T cell-dependent immune responses when relieved of substantial competition from other B cells. The failure to observe such B cells normally in late primary responses and in memory B cell populations is the result of competition, rather than an intrinsic inability of low affinity B cells.


Relationship between venous congestion and intraflap venous anatomy in DIEP flaps using contrast-enhanced magnetic resonance angiography.
Deep inferior epigastric artery perforator (DIEP) flap harvest is associated with a significant rate of venous congestion; however, the reason for this has not yet been fully explained. Contrast-enhanced magnetic resonance angiography enables detailed evaluation of both the arterial and venous anatomies. A retrospective review of DIEP flaps that underwent preoperative contrast-enhanced magnetic resonance angiography was performed. Outcomes were compared with preoperative radiologic reporting of contrast-enhanced magnetic resonance angiographic imaging, and anatomical data from the scans were also analyzed. Review of 54 DIEP flaps with venous system reporting was performed. Seven DIEP flaps suffered venous congestion, all of which were raised on perforators without direct connections between the venae comitantes and the main arborization of the superficial inferior epigastric vein. In the 47 DIEP flaps without venous congestion, 46 were raised on at least one perforator with a direct venous connection between the perforator venae comitantes and the main arborizations of the superficial inferior epigastric vein. There was an extremely significant association between the absence of a direct connection with the perforator venae comitantes on magnetic resonance angiography and the occurrence of venous congestion (p < 0.0001). Sixty-eight percent of all perforators had direct venous connections, which were significantly more likely to be located in the medial row. DIEP flaps elevated on perforators with venae comitantes with direct venous connections to the main arborization of the superficial inferior epigastric vein are significantly associated with a very low incidence of flap venous congestion. Contrast-enhanced magnetic resonance angiography allows detailed appraisal of the venous anatomy, which may minimize the risk of DIEP flap venous insufficiency and the need for salvage procedures.


Some electrical and pharmacological properties of gap junctions between adult ventricular myocytes.
Ventricular myocytes were isolated from adult rat hearts using the technique of Wittenberg and Robinson (Cell Tissue Res. 216: 231-251, 1981). These cells exhibited morphology, input resistance, time constant, and excitability expected for cells in intact cardiac tissue. Pairs of these cells were electronically coupled, and junctional conductance was unaffected by transjunctional potential or hyperpolarization of both cells. Brief exposure of cell pairs to medium equilibrated with 100% CO2 or containing 0.1 mM octanol quickly and reversibly decreased junctional conductance. We conclude that gap junctions between pairs of ventricular myocytes possess physiological properties like those of junctions in many other tissues. This preparation will be useful in evaluating drug action on junctional communication in heart.


[Response variability in pharmacotherapy].
The response obtained to drug administration can be modified by several factors which, from a synthetic point of view, can be classified into four basic groups: physical, chemical, biological and therapeutical. The first two can be verified and controlled by means of in-vitro test and, they must be known and solved before de final formulation is obtained. The other two factors, biological and therapeutical ones, introduce variables whose analysis concerns to the prescriptor. After this introduction, the variability in drug response is analyzed and discussed paying special attention to the pharmacokinetic and pharmacodynamic variability, analyzing the sources of such variability: environmental factors, factors depending of age, physical and genetical constitution, pathological states or drug interactions.


Selective Isomerization via Transient Thermodynamic Control: Dynamic Epimerization of trans to cis Diols.
Traditional approaches to stereoselective synthesis require high levels of enantio- and diastereocontrol in every step that forms a new stereocenter. Here, we report an alternative approach, in which the stereochemistry of organic substrates is selectively edited without further structural modification, a strategy with the potential to allow new classes of late-stage stereochemical manipulation and provide access to rare or valuable stereochemical configurations. In this work, we describe a selective epimerization of cyclic diols enabled by hydrogen atom transfer photocatalysis and boronic acid mediated transient thermodynamic control, selectively generating less stable cis products from the otherwise favored trans isomers. A range of substitution patterns and ring sizes are amenable to selective isomerization, including stereochemically complex polyols such as estriol, as well as syn to anti epimerization of acyclic vicinal diols. Moreover, this strategy has enabled the divergent epimerization of saccharide anomers, providing access to distinct sugar isomers from α- or β-configured glycosides.


Cortical map reorganization enabled by nucleus basalis activity.
Little is known about the mechanisms that allow the cortex to selectively improve the neural representations of behaviorally important stimuli while ignoring irrelevant stimuli. Diffuse neuromodulatory systems may facilitate cortical plasticity by acting as teachers to mark important stimuli. This study demonstrates that episodic electrical stimulation of the nucleus basalis, paired with an auditory stimulus, results in a massive progressive reorganization of the primary auditory cortex in the adult rat. Receptive field sizes can be narrowed, broadened, or left unaltered depending on specific parameters of the acoustic stimulus paired with nucleus basalis activation. This differential plasticity parallels the receptive field remodeling that results from different types of behavioral training. This result suggests that input characteristics may be able to drive appropriate alterations of receptive fields independently of explicit knowledge of the task. These findings also suggest that the basal forebrain plays an active instructional role in representational plasticity.


Cost-effectiveness analysis: can we reduce variability in costing methods?
The need for consistency and standardization of methods for economic appraisals has been recognized for some time and has led to the development of several sets of guidelines for economic evaluations and for costs. Despite this, considerable diversity is still apparent in applied studies. Some of these diversities might be defensible, and some might not. The objectives of this study are to explore sources of variations in the methods used in applied studies and to discuss the nature of these variations and the possibility of reducing some of them. We first use a systematic approach to identify the major sources of variation in costing methods used in applied economic evaluations. We then compare the methods used with the recommendations made in available guidelines. Four possible sources of variation are identified. The first is where guidelines do not agree in their recommendations; therefore, it is not surprising that applied studies use different methods. The second is where guidelines agree in principle but provide little detail on how to comply with their recommendations; and the third is where a particular methodological issue is not discussed in guidelines. The fourth reason is simply lack of compliance with accepted guidelines. Variability in costing methods used in applied studies raises questions about the validity of their results and makes it difficult to compare the results of different studies. We discuss the implications for the transferability and generalizability of results and suggest ways to minimize the variability in the methods so that the results of costing studies and economic evaluations can be of more value to policy-makers.


Characterization of beta-adrenergic receptors in duck cerebral cortex.
beta-adrenoceptor binding sites were characterized in duck cerebral cortex by an in vitro binding technique, using [3H]dihydroalprenolol ([3H]DHA) as a receptor-specific radioligand. The specific binding of [3H]DHA to duck cerebral cortical membranes was found to be rapid, stable, saturable, reversible, and of high affinity. Saturation analysis resulted in a linear Scatchard plot suggesting binding to a single class of receptor binding sites with high affinity (Kd = 1.18 nM) and high capacity (Bmax = 162 fmol/mg protein). Competition studies showed the following relative rank order of potency of various compounds to inhibit the [3H]DHA binding: antagonists--ICI 118,551 > S(-)-propranolol >> betaxolol, yohimbine, WB-4101, prazosin, mianserine; agonists--isoprenaline approximately equal to fenoterol > salbutamol >> clonidine, phenylephrine. The obtained data suggest that in duck cerebral cortex beta-adrenergic receptors (like those described in brains of chick and pigeon) are of the beta 2 subtype. This is in contrast to what has been reported for the mammalian brain, where--among beta-adrenoceptors--the beta 1 subtype is predominant.


Improving plant functional groups for dynamic models of biodiversity: at the crossroads between functional and community ecology.
The pace of on-going climate change calls for reliable plant biodiversity scenarios. Traditional dynamic vegetation models use plant functional types that are summarized to such an extent that they become meaningless for biodiversity scenarios. Hybrid dynamic vegetation models of intermediate complexity (hybrid-DVMs) have recently been developed to address this issue. These models, at the crossroads between phenomenological and process-based models, are able to involve an intermediate number of well-chosen plant functional groups (PFGs). The challenge is to build meaningful PFGs that are representative of plant biodiversity, and consistent with the parameters and processes of hybrid-DVMs. Here, we propose and test a framework based on few selected traits to define a limited number of PFGs, which are both representative of the diversity (functional and taxonomic) of the flora in the Ecrins National Park, and adapted to hybrid-DVMs. This new classification scheme, together with recent advances in vegetation modeling, constitutes a step forward for mechanistic biodiversity modeling.


The prevalence and impact of major life stressors among pathological gamblers.
Major traumatic events were discovered in the histories of 23% of pathological gamblers seeking hospital treatment. These high-trauma patients were compared with groups of gambler patients who had experienced insignificant, low, or moderate amounts of life trauma. High-trauma patients tended, as measured by standard psychometrics, to be more depressed, anxious, and avoidant in personality style; they were also more likely to be abusing alcohol or other drugs. In their discussion the authors focus on the concept of learned dysthymia, a chronic state of negative affect related to cumulative life trauma and seemingly instrumental in potentiating addictive euphoria.


Metallic Micro-Nano Network-Based Soft Transparent Electrodes: Materials, Processes, and Applications.
Soft transparent electrodes (TEs) have received tremendous interest from academia and industry due to the rapid development of lightweight, transparent soft electronics. Metallic micro-nano networks (MMNNs) are a class of promising soft TEs that exhibit excellent optical and electrical properties, including low sheet resistance and high optical transmittance, as well as superior mechanical properties such as softness, robustness, and desirable stability. They are genuinely interesting alternatives to conventional conductive metal oxides, which are expensive to fabricate and have limited flexibility on soft surfaces. This review summarizes state-of-the-art research developments in MMNN-based soft TEs in terms of performance specifications, fabrication methods, and application areas. The review describes the implementation of MMNN-based soft TEs in optoelectronics, bioelectronics, tactile sensors, energy storage devices, and other applications. Finally, it presents a perspective on the technical difficulties and potential future possibilities for MMNN-based TE development.


Self-reported daily walking time in COPD: relationship with relevant clinical and functional characteristics.
Quantifying physical activity in chronic obstructive pulmonary disease (COPD) is important as physical inactivity is related to poor health outcomes. This study analyzed the relationship between patients' self-reported daily walking time and relevant characteristics related to COPD severity. Pooled analysis was performed on data from four observational studies on which daily walking time was gathered from a personal interview. Patients were classified as physically inactive if walking time was <30 min/day. Walking times were described and compared according to several markers of disease severity. The mean daily walking time of 5,969 patients was 66 (standard deviation [SD] 47) min/day; 893 (15%) patients were inactive. A linear dose-response relationship was observed between walking time and the modified Medical Research Council (mMRC) dyspnea score, admissions, COPD assessment test (CAT), body mass index, airway obstruction, dyspnea, exacerbation (BODEx) index, and Charlson index (P<0.001). Daily walking times were lower in patients classified as Global Initiative for Chronic Obstructive Lung Disease (GOLD) B and D (P<0.001). Often, inactive patients had mMRC or Charlson index >3, post-bronchodilator forced expiratory volume in the first second <30% predicted, at least one hospitalization for COPD, classified as GOLD B or D, BODEx >4, and CAT score >30. Lower self-reported walking times are related to worse markers of disease severity in COPD.


Family planning and sexual behavior in the era of HIV/AIDS: the case of Nakuru District, Kenya.
Recently, the prevalence of contraceptive use has increased in Kenya. The twin risks of unwanted pregnancy and HIV/AIDS infection remain central concerns of reproductive health programs. However, we do not know how sexually active men and women perceive these risks, nor the strategies they consider appropriate to cope with these risks, nor the difficulties they face in trying to adopt appropriate sexual behaviors to minimize them. This study seeks to provide insights into perceptions, coping strategies, and constraints in the changing behavior of sexually active people in Nakuru District, Kenya. Twelve focus-group discussions were conducted, the results of which show that people in the study area consider the two risks to be serious problems, but that they neither use condoms within marriage nor refuse their partners sex even if they perceive a risk of acquiring HIV. These findings call for serious efforts toward fostering behavioral change in this area.


Fatigue in relatives of palliative patients.
The relatives' burdens in palliative care are considerable and may cause fatigue. The overall aim of this study was to gain a greater understanding of fatigue in relatives of patients cared for in palliative care settings. This study has a descriptive, comparative, and cross-sectional design. The sample consisted of relatives of all patients cared for in palliative care settings in Uppsala County during a specific day. Relatives completed a questionnaire consisting of the Multidimensional Fatique Inventory (MFI-20) and questions from the Karolinska Sleepiness Scale (KSS) and Karolinska Sleep questionnaire (KSQ). Relatives (n = 56) scored high on every dimension on the MFI-20 scale. Two significant negative correlations were found to exist between age and fatigue, with younger relatives reporting more mental fatigue (p < .01) and more reduced activity (p < .01) than older relatives. Relatives of patients in institutional care had higher values concerning mental fatigue (p < .01) and reduced motivation (p < .05). Relatives of mostly bedridden patients were significantly more tired but did not have significantly less motivation than relatives of mostly ambulatory patients. The findings imply that fatigue is highly prevalent in relatives of patients in palliative care. The sample in this study scored higher in comparison with norm values and also in comparison with relatives of patients with end-stage renal disease. Their scores were similar to those of cancer patients undergoing radiotherapy.


Factor XIII contrasts the effects of metalloproteinases in human dermal fibroblast cultured cells.
Matrix metalloproteinases (MMPs) are overexpressed in venous leg ulcers, determining a breakdown of the main extracellular matrix (ECM) components owing mainly to collagenase activities, and so playing a crucial role in ulcer pathogenesis. The authors studied the effects of coagulation factor XIII (FXIII), which cross-links collagen and other ECM components, in human fibroblast cultured cells in the presence and in the absence of matrix metalloproteinases from Clostridium histolyticum collagenase. Clostridium collagenase at concentrations of 2.0, 1.0, and 0.5 mg/mL was added to normal human dermal fibroblasts cultured in the presence of 0.0, 1.0, and 5.0 U/mL of FXIII concentrate (Fibrogammin P, Aventis Behring). Cell counting and metabolically active fibroblast evaluation in the cultures were monitored for 72 hours, by means of trypan-blue dye and MTT test, respectively. The MTT test showed that at the highest collagenase concentration (2.0 mg/mL), the cell number decreased more than 95% in 72 hours of treatment and no significant differences were observed regardless of the FXIII concentrations utilized. At lower collagenase concentration (1.0 mg/mL), in absence or in presence of FXIII (1.0 U/mL), the cell number decreased by about 80% in 72 hours. In contrast, in the presence of higher FXIII levels (5.0 U/mL), cells suffered globally significantly less collagenase effects (p = 0.011) and the gain was appreciable at each time tested. Finally, at 0.5 mg/mL of collagenase concentration, in the absence of FXIII, the cell number decreased by about 60% in 72 hours, whereas in presence of FXIII 1.0 U/mL and 5.0 U/mL, cells decreased significantly less, by about 35% and 20%, respectively (p < 0.025 and p < 0.01, respectively). These data were also confirmed by direct cell counting utilizing the trypan-blue test. Factor XIII contrasts effectively the detrimental action of Clostridium collagenases in human fibroblast cultured cells. These results support several in vivo reports about the effectiveness of its topical application in order to enhance the venous ulcer healing processes.


Mechanism of a reproducible accordion phenomenon: insights by optical coherence tomography visualization.
Pseudostenosis or 'accordion phenomenon' is a transient angiographic multifocal filling defect observed mostly during percutaneous coronary intervention, mainly in tortuous vessels. We describe a case of a reproducible accordion effect in the right coronary artery accompanied by only a mild clinical syndrome. Optical coherence tomography evaluation of this strange and fortunately completely reversible phenomenon is discussed.


How do polyunsaturated fatty acids lower plasma cholesterol levels?
For 30 years it has been known that linoleic acid can lower elevated cholesterol levels. Large increases in linoleic acid have been widely recommended as a way of reducing the risk of cardiovascular disease. Such recommendations have resulted in major dietary shifts in some countries, including the USA. Yet the precise characteristics of the linoleic acid molecule which confer on it cholesterol-lowering properties are unknown. gamma-Linolenic acid, the first essential fatty acid metabolite of linoleic acid, has been found to have cholesterol-lowering actions ca. 170 times greater than the parent molecule, suggesting that linoleic acid must be converted to gamma-linolenic acid to exert its desirable effects on cholesterol metabolism. Aging, sex, diabetes mellitus, alcohol, catecholamines and trans fatty acids and saturated fats can all modulate the delta-6-desaturase enzyme which converts linoleic acid to gamma-linolenic acid. This provides a possible unifying explanation for the actions of these known risk factors for cardiovascular disease.


Usefulness of computed tomographic coronary angiography in patients with acute chest pain with and without high-risk features.
The accuracy of 64-slice computed tomographic coronary angiography (CTA) and its ability to direct revascularization in patients with acute chest pain syndrome (ACPS) was investigated. A total of 107 patients with ACPS presenting to the emergency department and referred to cardiology were prospectively enrolled and underwent CTA. From the clinical features, the patients were categorized as having high-risk acute coronary syndrome features or no high-risk features. At the treating physician's discretion, the patients underwent risk stratification with either invasive coronary angiography (ICA) or technetium-99m single photon emission computed tomography. All tests were interpreted by experts unaware of the clinical information. All 52 patients with high-risk acute coronary syndrome features underwent ICA. Of the 55 patients with no high-risk features, 36 underwent single photon emission computed tomography and 19 underwent ICA. The patients were followed up until a decision regarding revascularization was made. Compared with ICA, the operating characteristics of CTA (per-patient analysis) were excellent, with a sensitivity of 98% (95% confidence interval [CI] 87% to 100%), specificity of 100% (95% CI 85% to 100%), positive predictive value of 100% (95% CI 90% to 100%), and negative predictive value of 97% (95% CI 80% to 100%). The agreement between CTA and routine testing (single photon emission computed tomography or ICA) was very good (kappa = 0.94). CTA correctly identified 40 patients (100%) who underwent revascularization and 61 (91.0%) who were treated medically (kappa = 0.88, 95% CI 0.79 to 0.97). In conclusion, CTA might represent a single modality that could be used to triage a wide spectrum of patients with ACPS and could have the potential to rule out coronary disease and identify those who might require revascularization.


Visualisation of edge effects in side-gated graphene nanodevices.
Using local scanning electrical techniques we study edge effects in side-gated Hall bar nanodevices made of epitaxial graphene. We demonstrate that lithographically defined edges of the graphene channel exhibit hole conduction within the narrow band of ~60-125 nm width, whereas the bulk of the material is electron doped. The effect is the most pronounced when the influence of atmospheric contamination is minimal. We also show that the electronic properties at the edges can be precisely tuned from hole to electron conduction by using moderate strength electrical fields created by side-gates. However, the central part of the channel remains relatively unaffected by the side-gates and retains the bulk properties of graphene.


A multicenter retrospective comparison of trauma in toy breeds versus giant breeds: A Veterinary Committee on Trauma registry study.
To retrospectively evaluate and stratify the differences in signalment, mechanisms, and severity of injury between toy and giant breed dogs. Retrospective, observational cohort study. Multicenter, university veterinary teaching hospital, and private referral hospitals contributing to Veterinary Committee on Trauma (VetCOT) patient registry. Two thousand seven hundred and five (2589 toy and 116 giant breed) dogs presented for trauma with complete data entries recruited into the Veterinary Committee on Trauma registry from September 1, 2013 through December 31, 2017. None. Injury etiology in toy breeds was predominantly blunt trauma (1532/2587 [59.2%]), commonly falling from a height or motor vehicle accident, whereas in giant breeds penetrating trauma was more common (71/116 [61.2%]). Eighty-seven percent (2231/2558) of toy breeds and 94.7% (108/114) giant breeds survived to discharge. When stratified by severity of injury (animal trauma triage [ATT] ≥ 5), mortality increased. Severely injured toy breeds had a 45.6% (200/438) survival rate, and severely injured giant breeds had a 62.5% (5/8) survival rate. Patient size did not impact survival in a logistic regression model; however, ATT score (odd ratio, 0.55; 95% CI, 0.52-0.58; P < 0.001), modified Glasgow Coma Scale (mGCS; odds ratio, 1.2; 95% CI, 1.11-1.32; P < 0.001), and base excess (odds ratio, 1.15; 95% CI, 1.09-1.22; P < 0.001) were predictive of nonsurvival. Surgical intervention was required in 743 of 2587 (29%) toy breeds and 65 of 116 (56%) giant breeds. Surgery was associated with an increased survival rate (odds ratio, 4.43; 95% CI, 2.45-8.83; P < 0.0001). Evaluation of a large, multicenter dataset showed that ATT score along with base excess, plasma lactate, and mGCS were predictors of mortality independent of patient size. Severely injured dogs, as defined by an ATT score ≥ 5, were less likely to survive, and toy breed dogs had a higher mortality rate than giant breeds in the subcategory.


Pantethine treatment is effective in recovering the disease phenotype induced by ketogenic diet in a pantothenate kinase-associated neurodegeneration mouse model.
Pantothenate kinase-associated neurodegeneration, caused by mutations in the PANK2 gene, is an autosomal recessive disorder characterized by dystonia, dysarthria, rigidity, pigmentary retinal degeneration and brain iron accumulation. PANK2 encodes the mitochondrial enzyme pantothenate kinase type 2, responsible for the phosphorylation of pantothenate or vitamin B5 in the biosynthesis of co-enzyme A. A Pank2 knockout (Pank2(-/-)) mouse model did not recapitulate the human disease but showed azoospermia and mitochondrial dysfunctions. We challenged this mouse model with a low glucose and high lipid content diet (ketogenic diet) to stimulate lipid use by mitochondrial beta-oxidation. In the presence of a shortage of co-enzyme A, this diet could evoke a general impairment of bioenergetic metabolism. Only Pank2(-/-) mice fed with a ketogenic diet developed a pantothenate kinase-associated neurodegeneration-like syndrome characterized by severe motor dysfunction, neurodegeneration and severely altered mitochondria in the central and peripheral nervous systems. These mice also showed structural alteration of muscle morphology, which was comparable with that observed in a patient with pantothenate kinase-associated neurodegeneration. We here demonstrate that pantethine administration can prevent the onset of the neuromuscular phenotype in mice suggesting the possibility of experimental treatment in patients with pantothenate kinase-associated neurodegeneration.


Does the Time of Day Play a Role in the Acute Effect of p-Synephrine on Fat Oxidation Rate during Exercise in Women? A Randomized, Crossover and Double-Blind Study.
p-Synephrine is deemed a safe and effective substance to increase fat utilization during exercise of low-to-moderate intensity in men but not in women. Additionally, the existence of a diurnal variation in substrate utilization has been documented during exercise with enhanced fat oxidation in the evening compared with early morning. However, it remains unknown whether there is an interaction between the effect of p-synephrine and the time of the day on fat oxidation during exercise. This study aimed to evaluate the effect of the acute ingestion of 3 milligram of p-synephrine per kilogram of body mass (mg/kg) on fat oxidation during exercise of increasing intensity when the exercise is performed in the morning vs. the evening. Using a randomized, double-blind, placebo-controlled experimental design, 16 healthy and active women performed four identical exercise trials after the ingestion of 3 mg/kg of p-synephrine and 3 mg/kg of a placebo (cellulose) both in the morning (8-10 am) and in the evening (5-7 pm). In the exercise trials, the substances were ingested 60 min before an incremental test on a cycle ergometer with 3 min stages at workloads from 30 to 80% of maximal oxygen uptake (VO2max). Substrate oxidation rates were measured by indirect calorimetry. In each trial, the maximum rate of fat oxidation (MFO) and the intensity that elicited MFO (Fatmax) were measured. A two-way analysis of variance (time-of-the day × substance) was used to detect differences among the trials. With the placebo, MFO was 0.25 ± 0.11 g/min in the morning and 0.24 ± 0.07 g/min in the evening. With p-synephrine, MFO was 0.26 ± 0.09 g/min in the morning and 0.21 ± 0.07 g/min in the evening. There was no main effect of substance (p = 0.349), time of day (p = 0.186) and the substance × time of day (p = 0.365) on MFO. Additionally, Fatmax was reached at a similar exercise intensity with the placebo (41.33 ± 8.34% VO2max in the morning and 44.38 ± 7.37% VO2max in the evening) and with p-synephrine (43.33 ± 7.24% VO2max in the morning and 45.00 ± 7.43% VO2max in the evening), irrespective of the time of day with no main effect of substance (p = 0.633), time of day (p = 0.191), or interaction (p = 0.580). In summary, the acute intake of 3 mg/kg of p-synephrine before exercise did not increase MFO and Fatmax, independently of the time of day, in female athletes. This indicates that the time of day is not a factor explaining the lack of effectiveness of this substance to enhance fat oxidation during aerobic exercise in women.


An animal study on the effect of topically administered ambroxol for dry eye.
To evaluate the effect of 0.2% ambroxol eye drop on tear secretion and corneal healing on a rabbit dry eye model, and to delineate potential underlying mechanisms. A mixed mechanism dry eye model was created using 12 healthy New Zealand rabbits by excision of the main lacrimal glands, Harderian gland and nictitating membrane. Establishment of the model was confirmed by the decrease of Schirmer I and increase of corneal fluorescein staining scores. Two weeks after model creation, the rabbits were randomly and evenly divided into NaCl, 0.1% sodium hyaluronate and 0.2% ambroxol groups. Each group was administered the respective eye drops 4 times a day for four weeks. The Schirmer I test and corneal fluorescein staining were performed at two and four weeks. After four weeks of treatment, the animals were sacrificed and the conjunctiva and eyelid specimens collected. Inflammatory factors IL-8, TNF-α, and goblet cell specific mucin MUC5AC were measured by ELISA while the lid meibomian gland was evaluated by oil red O staining. Compared with the baseline, 2 weeks after the surgery, Schirmer I test value decreased significantly (20.35 ± 5.18 mm/5 min vs 13.95 ± 4.64 mm/5 min, p < 0.01), and the fluorescein staining score increased significantly (0.5 ± 0.6 vs 5.5 ± 1.4, p < 0.01). After four weeks of treatment, compared with the NaCl and sodium hyaluronate groups, tear secretion in ambroxol group increased significantly (p < 0.01), while the corneal fluorescence staining score decreased significantly (p < 0.01). In the conjunctival tissue, significant decrease was seen in TNF-α (p < 0.01) and IL-8 [p (unilateral) < 0.05] concentrations in ambroxol group, and significant increase in MUC5AC concentration (p < 0.01) in ambroxol group as well. The lipid content in the lid meibomian glands appeared increased after the administration of ambroxol. The present rabbit dry eye model study demonstrated potentials of topically administered 0.2% ambroxol in stimulating tear and mucin secretion, inhibiting ocular surface inflammation, promoting corneal healing, and possibly augmenting meibomian gland lipid production.


[Social representation of the community therapist in the Brazilian Unified Health System].
The approval of the National Policy of Integrative and Complementary Practices fosters the provision of Community Therapy in the Brazilian Unified Health System (SUS). This initiative seeks to develop the necessary competencies to attend to the psychosocial demands in the professionals and the community leadership and to build support networks in order to extend the efficacy of Primary Health Care. This study aims to describe the social representation on the community therapist prepared by health care professionals employed at SUS. Semi-structured interviews were conducted with 27 professionals who were trained in Community Therapy in 2009 by the State Health Department of Santa Catarina in partnership with the Ministry of Health. Data analysis was carried out by descending hierarchical classification. The results revealed that there is a social representation among the professionals regarding what it signifies to be a community therapist, seen as someone who humanizes interpersonal relations in the health care sector. However, Primary Health Care professionals still subscribe to a less horizontalized group practice model than professionals working at the secondary level of care, represented in this study by the Psychosocial Care Centers (CAPS).


[Cytological characteristics of the human periodontal fibroblasts].
This review examines current concepts of functional morphology and molecular biology of periodontal fibroblasts. These cells appear to be the major cellular elements of human periodontium that realize its functions. Recent evidence on fibroblast structure, regeneration, synthetic and secretory activity, adhesion to various matrix components, migration, response to hormones, cytokines, growth factors and microbial products as well as on their interaction with other cellular elements of periodontium, is reviewed. On the basis of the newest findings on cellular and molecular biology, the concept of the central role of fibroblasts in the local network of cytokine regulation that controls the integrated function of periodontal cells, is formulated.


Novel agents in development for the treatment of depression.
There are several investigational drugs in development for the treatment of depression. Some of the novel antidepressants in development target monoaminergic neurotransmission in accordance with the "monoamine hypothesis of depression." However, the current conceptualization of antidepressant actions is that it is the downstream effects on protein synthesis and neuroplasticity that account for therapeutic efficacy, rather than the immediate effects on synaptic monoamine levels. Thus, a number of novel agents in development directly target components of this "neuroplasticity hypothesis of depression," including hypothetically overactive glutamatergic neurotransmission and dysfunctional hypothalamic-pituitary-adrenal (HPA) axis functioning.


Helicobacter pylori, gastrointestinal symptoms, and metabolic control in young type 1 diabetes mellitus patients.
The role of Helicobacter pylori infection in metabolic control and gastrointestinal symptoms in type 1 diabetes mellitus (DM1) patients has been debated. The aim of this study was to investigate the prevalence of H pylori, of the more cytotoxic Cag-A-positive strains, and the effects of infection on gastrointestinal symptoms and metabolic control in young DM1 patients. Research Design and Methods. H pylori infection was investigated by using the 13C-urea breath test in 121 DM1 patients (65 males, 56 females; mean age: 15 +/- 6 years) and 147 matched controls. In positive patients, an assay for specific immunoglobulin G against Cag-A was performed. Glycosylated hemoglobin A, daily insulin requirement, and duration of illness were established; a questionnaire concerning the presence of dyspeptic symptoms was administered. No difference in H pylori infection rate between patients and controls was observed. Thirty-four (28.1%) of 121 patients and 43 (29.25%) of 147 controls were infected. Twenty-one patients and 24 controls were positive for Cag-A. Glycosylated hemoglobin A, daily insulin requirement, and duration of illness were not affected by infection nor by Cag-A status. Among gastrointestinal symptoms, only halitosis was related to H pylori infection, but this association disappeared after correction for age. Positive patients with halitosis showed a worse glycemic control than uninfected patients with halitosis. H pylori infection and Cag-A-positive strains do not affect metabolic control in DM1 patients. With regard to gastrointestinal symptoms studied, H pylori infection, when present in participants with halitosis, seems to predict a worse metabolic control than in H pylori-negative patients with halitosis.


Calculation and Interpretation of Substrate Assimilation Rates in Microbial Cells Based on Isotopic Composition Data Obtained by nanoSIMS.
Stable isotope probing (SIP) combined with nano-scale secondary ion mass spectrometry (nanoSIMS) is a powerful approach to quantify assimilation rates of elements such as C and N into individual microbial cells. Here, we use mathematical modeling to investigate how the derived rate estimates depend on the model used to describe substrate assimilation by a cell during a SIP incubation. We show that the most commonly used model, which is based on the simplifying assumptions of linearly increasing biomass of individual cells over time and no cell division, can yield underestimated assimilation rates when compared to rates derived from a model that accounts for cell division. This difference occurs because the isotopic labeling of a dividing cell increases more rapidly over time compared to a non-dividing cell and becomes more pronounced as the labeling increases above a threshold value that depends on the cell cycle stage of the measured cell. Based on the modeling results, we present formulae for estimating assimilation rates in cells and discuss their underlying assumptions, conditions of applicability, and implications for the interpretation of intercellular variability in assimilation rates derived from nanoSIMS data, including the impacts of storage inclusion metabolism. We offer the formulae as a Matlab script to facilitate rapid data evaluation by nanoSIMS users.


Vascular tube formation on matrix metalloproteinase-1-damaged collagen.
Connective tissue damage and angiogenesis are both important features of tumour growth and invasion. Here, we show that endothelial cells maintained on a three-dimensional lattice of intact polymerised collagen formed a monolayer of cells with a cobblestone morphology. When the collagen was exposed to organ culture fluid from human basal cell tumours of the skin (containing a high level of active matrix metalloproteinase-1 (MMP-1)), degradation of the collagen matrix occurred. The major degradation products were the $3 over 4$- and $1 over 4$-sized fragments known to result from the action of MMP-1 on type I collagen. When endothelial cells were maintained on the partially degraded collagen, the cells organised into a network of vascular tubes. Pretreatment of the organ culture fluid with either tissue inhibitor of metalloproteinase-1 (TIMP-1) or neutralising antibody to MMP-1 prevented degradation of the collagen lattice and concomitantly inhibited endothelial cell organisation into the vascular network. Purified (activated) MMP-1 duplicated the effects of skin organ culture fluid, but other enzymes including MMP-9 (gelatinase B), elastase or trypsin failed to produce measurable fragments from intact collagen and also failed to promote vascular tube formation. Together, these studies suggest that damage to the collagenous matrix is itself an important inducer of new vessel formation.


Early syllabic segmentation of fluent speech by infants acquiring French.
Word form segmentation abilities emerge during the first year of life, and it has been proposed that infants initially rely on two types of cues to extract words from fluent speech: Transitional Probabilities (TPs) and rhythmic units. The main goal of the present study was to use the behavioral method of the Headturn Preference Procedure (HPP) to investigate again rhythmic segmentation of syllabic units by French-learning infants at the onset of segmentation abilities (around 8 months) given repeated failure to find syllabic segmentation at such a young age. The second goal was to explore the interaction between the use of TPs and syllabic units for segmentation by French-learning infants. The rationale was that decreasing TP cues around target syllables embedded in bisyllabic words would block bisyllabic word segmentation and facilitate the observation of syllabic segmentation. In Experiments 1 and 2, infants were tested in a condition of moderate TP decrease; no evidence of either syllabic or bisyllabic word segmentation was found. In Experiment 3, infants were tested in a condition of more marked TP decrease, and a novelty syllabic segmentation effect was observed. Therefore, the present study first establishes early syllabic segmentation in French-learning infants, bringing support from a syllable-based language to the proposal that rhythmic units are used at the onset of segmentation abilities. Second, it confirms that French-learning infants are sensitive to TP cues. Third, it demonstrates that they are sensitive to the relative weight of TP and rhythmic cues, explaining why effects of syllabic segmentation are not observed in context of high TPs. These findings are discussed in relation to theories of word segmentation bootstrapping, and the larger debate about statistically- versus prosodically-based accounts of early language acquisition.


Energy metabolism in Capnocytophaga ochracea.
Among the microflora of the gingival sulcus are members of the genus Capnocytophaga which have been implicated as possible etiological agents of juvenile periodontitis and systemic infectious diseases. In this study, the pathway used by C. ochracea strain 25 for generating energy from glucose was investigated. When grown in a complex medium supplemented with glucose and NaHCO(3), the major end products formed were acetate (4.6 mmol), succinate (11.0 mmol), pyruvate (4.3 mmol), and oxalacetate (3.6 mmol), and the molar growth yield was 58. Addition of yeast extract to the growth medium caused (i) an increase in acetate (9.2 mmol) and succinate (14.3 mmol), (ii) a decrease in pyruvate (0 mmol) and oxalacetate (1.1 mmol), and (iii) the molar growth yield increased to 75. Glucose was transported by a phosphoenolpyruvate:phosphotransferase system and then catabolized to phosphoenolpyruvate by enzymes of the Embden-Meyerhof-Parnas pathway. No activities were detected for the key enzymes of the Warburg-Dickens, Entner-Douderoff, or hexose phosphoketolase pathways. During growth in the yeast extract-supplemented medium, approximately 37% of the phosphoenolpyruvate carbon was converted to acetate by pyruvate kinase, a pyruvate-decarboxylating enzyme activity, and acetate kinase; the remaining 63% was converted to succinate via phosphoenolpyruvate carboxykinase, malate dehydrogenase, fumarate hydratase, and fumarate reductase.


Loss of heterozygosity at chromosome segments 8p22 and 8p11.2-21.1 in transitional-cell carcinoma of the urinary bladder.
To identify the putative tumor-suppressor gene (TSG) involved in transitional-cell carcinoma (TCC) of the urinary bladder, we undertook an allelotyping analysis in 48 cases of TCC. Relatively high percentages of allelic loss were found in 2p (5 of 23, 21.7%), 8p (9 of 21, 42.9%), 9p (4 of 20, 20.0%), 12q (6 of 28, 21.4%), 15q (1 of 5, 20%; 4 of 20, 20%), 17p (7 of 26, 26.9%) and 22q (6 of 23, 26.1%). On the basis of these results, fine-deletion mapping was performed on chromosome 8 in 52 cases by PCR of 15 microsatellite markers. Two distinct regions of common deletion were found. A 10 cM telomeric region was located to 8p22, defined by D8S511 and D8S258. A 17 cM centromeric region was located to 8p11.2-21.1, flanked by D8S298 and D8S535. The distance between the telomeric and the centromeric regions of common deletion was 3 cM. Loss of heterozygosity of 8p22 was frequently observed in tumors of high grade or advanced stage.


[Drug addicts' liver].
To assess condition of the liver in drug abusers. Clinicobiochemical, immunological, virological and morphological hepatic tests were made in 144 patients with different forms of drug addiction. Hepatic diseases are rather common in drug addicts. They have some specific clinical features: weak clinical symptoms and laboratory ++indications, high incidence of viral hepatitides markers, repeated infection, initially absent definite evidence on immunological status disturbance, predominant morphologically inactive forms. Symptoms of hepatic disorders were found both in the period of active abuse and in abstinence. Young people with psychopathological behavior should be examined and followed up for detection of drug addiction and concomitant liver diseases.


Collateral growth in the peripheral circulation: a review.
Arterial occlusive diseases are a major cause of morbidity and death in the United States. The enlargement of pre-existing vessels, which bypass the site of arterial occlusion, provide a natural way for the body to compensate for such obstructions. Individuals differ in their capacity to develop collateral vessels. In recent years much attention has been focused upon therapy to promote collateral development, primarily using individual growth factors. Such studies have had mixed results. Persistent controversies exist regarding the initiating stimuli, the processes involved in enlargement, the specific vessels that should be targeted, and the most appropriate terminology. Consequently, it is now recognized that more research is needed to extend our knowledge of the complex process of collateral growth. This basic science review addresses five questions essential in understanding current problems in collateral growth research and the development of therapeutic interventions.