An extracellular thermo-alkali-stable laccase from Bacillus tequilensis SN4, with a potential to biobleach softwood pulp.
Degradation of residual lignin in kraft pulp by chemical bleaching is implicated in causing environmental pollution. The use of thermo- and alkali-tolerant bacterial laccases is considered to be important biological alternative to chemical processing. Laccases from Bacillus species have shown promise in this respect but their intracellular/spore bound presence make their industrial application economically unfeasible. We report here on a novel extracellular active thermo-alkali-stable laccase (SN4 laccase) which is active at 90 °C and pH 8.0 using 2,6-dimethoxyphenol as substrate from Bacillus tequilensis SN4. SN4 laccase retained 27 % activity for 5 min at 100 °C and more than 80 % activity for 24 h at 70 °C. The enzyme is also stable at a higher pH (9.0-10.0). Enzyme production was optimized by submerged fermentation. Relatively high yields (18,356 nkats ml-1) of SN4 laccase was obtained in a medium containing 650 μM MnSO4, 350 μM FeSO4, and 3.5 % ethanol. A 764-fold increase in laccase activity was observed under optimal conditions. In addition, reduction in kappa number and increase in brightness of softwood pulp by 28 and 7.6 %, respectively, were observed after treatment with SN4 laccase without a mediator. When N-hydroxybenzotriazole was used as a mediator, the kappa number was decreased to 47 % and brightness was increased to 12 %.


Comparison of the SRK II formula and other second generation formulas.
A simple modification of the SRK formula was developed for use with extreme axial length cases (short and long eyes) to maximize prediction accuracy in these groups. For "average" eyes (over 75% of all cases), SRK needed no modifications to maintain maximum predictive accuracy. The new, modified SRK formula (SRK II) was compared with current second generation formulas and the Binkhorst formula. The SRK II formula, while maintaining the simplicity and ease of the SRK, was comparable to and in some cases superior to the other formulas. Overall, 80.0% of 2,068 posterior chamber intraocular lenses from seven different manufacturers demonstrated less than one diopter of prediction error and only 0.5% had three or more diopters of error. In short eyes (less than 22 mm), 74.0% were corrected to within one diopter and less than 2.0% had three or more diopters of error. In long eyes (greater than or equal to 24.5 mm), 78.0% of cases demonstrated less than one diopter of error and less than 1.0% had three or more diopters of error. Although the SRK II formula is incorporated in most new A-scan units, the modifications are so simple that surgeons can take the standard SRK predictions and mentally calculate the modifications for extreme cases.


Impact of nocturia on sleep and quality of life: a brief, selected review for the International Consultation on Incontinence Research Society (ICI-RS) nocturia think tank.
Nocturia, the need to awaken at night to void, is a highly prevalent disorder that negatively affects nocturnal sleep, increases daytime tiredness, and adversely impacts quality of life. In this selective review, we provide the reader an overview of current work in this area. From the perspective of disturbed sleep, two divergent perspectives have emerged from the literature when discussing nocturia. The first is that a patient awakens because of an urge to urinate. The second is that a patient awakens during the night for some reason unrelated to urinary urge (e.g., an awakening from an environmental source or from intrinsic lightening of sleep) and then decides to void while awake. In the few studies that have inquired about nocturia as a cause of awakenings, nocturia often ranks above the traditional psychological or physical factors. Not only is nocturia likely to disrupt sleep, but it may impact waking quality of life as well. A number of generic and nocturia-related questionnaires have been used to quantify the effect of nocturia on quality of life. In this short paper, we introduce the reader to several key studies in these important areas.


Factor structure of the Children's Behavior Questionnaire in children with Williams syndrome.
To examine the factor structure of temperament in 5-10-year-olds with Williams syndrome, an exploratory factor analysis was conducted on the responses of parents of 192 children on the children's behavior questionnaire. Four factors were identified. Two corresponded to factors reported for typically developing children: effortful control and extraversion/surgency and two corresponded to the temperament constructs of withdrawal/inhibition and irritability/frustration and activity, observed in typically developing infants. Parents of 109 of the 192 participants also completed the anxiety disorders interview schedule, parent version. Children with an anxiety disorder other than specific phobia differed significantly from children without an anxiety disorder on all factors except extraversion/surgency. Children with attention deficit hyperactivity disorder (ADHD) differed significantly from children without ADHD on effortful control and extraversion/surgency.


Role of prolactin in the recovered T-cell development of early partially decapitated chicken embryo.
Although different experimental approaches have suggested certain regulation of the mammalian immune system by the neuroendocrine system, the precise factors involved in the process are largely unknown. In previous reports, we demonstrated important changes in the thymic development of chickens deprived of the major neuroendocrine centers by the removal of embryonic prosencephalon at 33-38 hr of incubation (DCx embryos) (Herradón et al., 1991; Moreno et al., 1995). In these embryos, there was a stopping of T-cell maturation that resulted in an accumulation of the most immature T-cell subsets (CD4-CD8- cells and CD4-CD8lo cells) and, accordingly, in decreased numbers of DP (CD4+CD8+) thymocytes and mature CD3+TcRalphabeta+ cells, but not CD3+TcRgammadelta lymphocytes. In the present work, we restore the thymic histology as well as the percentage of distinct T-cell subsets of DCx embryos by supplying recombinant chicken prolactin, grafting of embryonic pituitary gland, or making cephalic chick-quail chimeras. The recovery was not, however, whole and the percentage of CD3+TcRalphabeta+ thymocytes did not reach the normal values observed in 17-day-old control Sham-DCx embryos. The results are discussed on the basis of a key role for prolactin in chicken T-cell maturation. This hormone could regulate the transition of DN (CD4 CD8 ) thymocytes to the DP (CD4+CD8+) cell compartment through its capacity for inducing IL-2 receptor expression on the former.


The Association Between Apolipoprotein E Gene Polymorphism and In-Stent Restenosis After Extracranial and Intracranial Artery Stenting.
Neo-atherosclerosis plays a vital role in the incidence of in-stent restenosis (ISR) after extracranial and intracranial artery stenting, and Apolipoprotein (ApoE) gene polymorphism has been reported to be closely related to the occurrence and development of atherosclerosis. The present study aims to investigate the association between ApoE gene polymorphism and ISR after extracranial and intracranial artery stenting. A total of 169 patients with successful stent implantation were included in this study. ApoE genotypes were obtained during the postoperative follow-up. Color Doppler ultrasonography of cervical artery or head and neck CT angiography (CTA) was performed on the 1,3,6 and 12 months and then yearly in the clinical follow-up. Multivariate Cox regression analysis of independent risk factors was performed to evaluate the ISR. Kaplan-Meier curves were generated to compare the restenosis -free rate among the patients with different ApoE genotypes. Of the 169 patients, 43 (43/169, 25.4%) developed ISR after a mean follow-up period of 10.4 months (1-35 months). Multivariate analysis showed that genotype E4/E4 (hazard ratio 3.305, P = 0.031, 95% confidence interval 1.118-9.773) and degree of stenosis >90% (hazard ratio 5.083, P = 0.001, 95% confidence interval 1.938-13.327) were significant determinants of ISR. ApoE gene polymorphism is closely related to the incidence of ISR after extracranial and intracranial artery stenting, and the genotype E4/E4 is an independent risk factor for ISR.


Hepatocyte-specific deletion of peroxisomal protein PEX13 results in disrupted iron homeostasis.
Peroxisomes are organelles, abundant in the liver, involved in a variety of cellular functions, including fatty acid metabolism, plasmalogen synthesis and metabolism of reactive oxygen species. Several inherited disorders are associated with peroxisomal dysfunction; increasingly many are associated with hepatic pathologies. The liver plays a principal role in regulation of iron metabolism. In this study we examined the possibility of a relationship between iron homeostasis and peroxisomal integrity. We examined the effect of deleting Pex13 in mouse liver on systemic iron homeostasis. We also used siRNA-mediated knock-down of PEX13 in a human hepatoma cell line (HepG2/C3A) to elucidate the mechanisms of PEX13-mediated regulation of hepcidin. We demonstrate that transgenic mice lacking hepatocyte Pex13 have defects in systemic iron homeostasis. The ablation of Pex13 expression in hepatocytes leads to a significant reduction in hepatic hepcidin levels. Our results also demonstrate that a deficiency of PEX13 gene expression in HepG2/C3A cells leads to decreased hepcidin expression, which is mediated through an increase in the signalling protein SMAD7, and endoplasmic reticulum (ER) stress. This study identifies a novel role for a protein involved in maintaining peroxisomal integrity and function in iron homeostasis. Loss of Pex13, a protein important for peroxisomal function, in hepatocytes leads to a significant increase in ER stress, which if unresolved, can affect liver function. The results from this study have implications for the management of patients with peroxisomal disorders and the liver-related complications they may develop.


Sub-Ångstrom electric field measurements on a universal detector in a scanning transmission electron microscope.
Scanning transmission electron microscopy (STEM) excels in accessing atomic-scale structure and chemistry. Enhancing our ability to directly image the functionalities of local features in materials has become one of the most important topics in the future development of STEM. Recently, differential phase contrast (DPC) imaging has been utilized to map the internal electric and magnetic fields in materials from nanoscale features such as p-n junctions, skyrmions, and even from individual atoms. Here, we use an ultra-low noise SCMOS detector in as the diffraction plane camera to collect four-dimensional (4D) datasets. The high angular resolution, efficient high-SNR acquisition, and modifiability of the camera allow it to function as a universal detector, where STEM imaging configurations, such as DPC, bright field, annular bright field, and annular dark field can all be reconstructed from a single 4D dataset. By examining a distorted perovskite, DyScO3, which possesses projected lattice spacings as small as 0.83 Å, we demonstrate DPC spatial resolution almost reaching the information limit of a 100 keV electron beam. In addition, the perovskite has ordered O-coordinations with alternating octahedral tilts, which can be quantitatively measured with single degree accuracy by taking advantage of DPC's sensitivity to light atoms. The results, acquired on a standard Ronchigram camera as opposed to a specialized DPC detector, open up new opportunities to understand and design functional materials and devices that involve lattice and charge coupling at nano- and atomic-scales.


Retracted: Evaluation of Teachers' Educational Technology Ability Based on Fuzzy Clustering Generalized Regression Neural Network.
[This retracts the article DOI: 10.1155/2021/1867723.].


Salt effects on the denaturation of DNA. IV. A calorimetric study of the helix-coil conversion of the alternating copolymer poly[d(A-T)].
The enthalpy deltaH, entropy deltaS, and the temperature Tm of the conformational transition of poly[d (A-T)] from the ordered to the randomly oriented state have been determined at pH 6.8 with the help of an adiabatic differential scanning calorimeter in Na2SO4 solutions of increasing ionic strength. Spectrophotometric denaturation experiments supplemented the calorimetric measurements. All thermodynamic parameters were found to vary strongly with salt concentration: both deltaH and Tm increase linearly with the logarithm of the mean molal activity alpha plus or minus of Na2SO4. However, whereas the dependence of Tm on salt activity remains linear over the entire salt concentration range employed deltaH decreases abruptly in the most concentrated Na2SO4 solutions. The entropy of melting changes with salt concentration in a pattern similar to that displayed by deltaH. The data on deltaH as well as data derived from the maximum slopes of the calorimetric heat denaturation curves were used to calculate the cooperative length Lh, the stacking free energy epsilon, and the cooperativity parameter sigma of poly[d(A-T)] as a function of ionic strength. Lh decreases with increasing salt concentration whereas sigma increases. Epsilon assumes more positive values with increasing salt molality. These changes then are in agreement with the generally held belief that an increase in salt concentration leads to an increase in the "loop" content of the copolymer.


Evidence for distinct pathways in rabbit renal brush-border membrane vesicles for the transport of unsubstituted and alpha-hydroxysubstituted aliphatic monocarboxylic acids.
We evaluated the effects of unsubstituted and hydroxymonocarboxylic acids on the kinetics of Na+-dependent L-lactate uptake in brush-border membrane vesicles prepared from the whole cortex of rabbit kidney. Acetate, propionate, and butyrate reversibly inhibited Na+-dependent L-lactate influx with [I]0.5 values of 5.5, 0.50, and 0.25 mM, respectively. Dixon plots (1/V versus acetate, propionate, and butyrate) were curved concavely downward, indicating partial inhibition. The Hill coefficients were approximately 1.0, suggesting that these anions interact at a single site on the Na+-L-lactate cotransporter. Acetate and the two other unsubstituted short-chain fatty acids tested decreased Na+-dependent L-lactate influx by increasing Km and decreasing Vmax, indicating mixed-type inhibition. In contrast, Na+-dependent L-lactate uptake was competitively inhibited by alpha-hydroxybutyrate and D-lactate. Finally, evidence is presented to show that D-lactate and alpha-hydroxybutyrate are mutually exclusive inhibitors of Na+-dependent L-lactate influx. Results from this and recent studies are interpreted as indicating that distinct transport systems serve for unsubstituted and alpha-hydroxymonocarboxylic acids in renal brush-border membrane vesicles.


Growth of sulfate-reducing bacteria with solid-phase electron acceptors.
Hannebachite (CaSO3 x 0.5H2O), gypsum (CaSO4 x 2H2O), anglesite (PbSO4), and barite (BaSO4) were tested as electron acceptors for sulfate-reducing bacteria with lactate as the electron donor. Hannebachite and gypsum are commonly associated with flue gas desulfurization products, and anglesite is a weathering product found in lead mines. Barite was included as the most insoluble sulfate. Growth of sulfate-reducing bacteria was monitored by protein and sulfide (dissolved H2S and HS-) measurements. Biogenic sulfide formation occurred with all four solid phases, and protein data confirmed that bacteria grew under these electron acceptor conditions. Sulfide formation from gypsum was almost comparable in rate and quantity to that produced from soluble sulfate salt (Na2SO4); hannebachite reduction to sulfide was not as fast. Anglesite as the electron acceptor was also reduced to sulfide in the solution phase and galena (PbS) was detected in solids retrieved from spent cultures. Barite as the electron acceptor supported the least amount of growth and H2S formation. The results demonstrate that low-solubility crystalline phases can be biologically reactive under reducing conditions. Furthermore, the results demonstrate that galena precipitation through sulfide production by sulfate-reducing bacteria serves as a lead enrichment mechanism, thereby also alleviating the potential toxicity of lead. In view of the role of acidophilic thiobacilli in the oxidation of sulfides, the present work accentuates the role of anaerobic and aerobic microbes in the biogeochemical cycling of solid-phase sulfates and sulfides.


[Lipids of plasmamembranes and of mitochondria in rat liver after intoxication with paraoxon (author's transl)].
0.426 mg/kg Paraoxon was applicated to female Sprague-Dawley rats. 4, 10 and 24 h after poisoning, cholesterol, glyceride and phospholipid content was measured in liver plasma membranes and mitochondria. After 4 h, cholesterol content of plasma membranes was significantly lower. Phospholipid content of plasma membranes was significantly higher than control values at all times of investigation, contents of neutral lipids and glycerides were also higher, but not significantly. In mitochondria, no significant difference of cholesterol content could be detected. Glyceride content was lower after 4 and 10 h, but phospholipid content higher at all experimental times. Differences found in cholesterol and phospholipid content of plasma membranes are discussed also in view of higher serum GOT, GPT and CPK activities known from other investigations. The differences in cholesterol and phospholipid content, their degree and their timing, which agrees with the timing of enzyme leakage, suggest that lipid composition of the plasma membrane may be one of the parameters which determine membrane permeability after organophosphate poisoning.


Cardioprotective effect of cinnamaldehyde pretreatment on ischemia/ reperfusion injury via inhibiting NLRP3 inflammasome activation and gasdermin D mediated cardiomyocyte pyroptosis.
Cinnamaldehyde (CD) is one of the most important active compounds derived from Cinnamomum cassia and showed multiple biological activities. Accumulating evidence has shown that the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome significantly contributes to sterile inflammatory response and gasdermin D (GSDMD)-mediated pyroptosis in myocardial ischemia/reperfusion injury (MI/RI). Whether CD has any influence on NLRP3 inflammasome activation and pyroptosis during myocardial I/R injury remains unknown. In the present study, we investigated the cardioprotective effect of CD via establishing the MI/RI rats' model by ligating the left anterior descending coronary artery for 30 min ischemia followed by 120 min reperfusion. Sprague-Dawley rats were intragastrically administered with CD (45 and 90 mg/kg/d) or vehicle for 7 successive days before ligation of the coronary artery to evoke MI/RI. The results found that CD significantly improved cardiac diastolic function, decreased cardiac infarct size and myocardial injury enzymes, inhibited cardiomyocyte apoptosis, attenuated cardiac structure abnormality, and mitigated oxidative stress and inflammatory response. We also found that MI/RI activated the NLRP3 inflammasome as evidenced by the upregulation levels of NLRP3, pro-caspase-1, caspase-1, and ASC proteins and mRNA. Importantly, MI/RI could trigger cardiomyocyte pyroptosis by increased DNA fragmentation, membrane pore formation, and mitochondrial swelling as well as increased levels of pyroptosis-related proteins and mRNA, including GSDMD, IL-18, and IL-1β. As expected, all these deleterious alterations were reversed by CD pretreatment. Our findings demonstrated that CD showed an outstanding cardioprotective effect via inhibiting NLRP3 inflammasome activation and GSDMD-mediated cardiomyocyte pyroptosis, which has a promising application value and development prospect against myocardial I/R injury in the future.


Accurate quantification of high-purity uranium in coatings by small solid angle method.
Aiming at quantifying high-purity uranium (235U/236U/238U) in coatings, a series of experiments were carried out by a dedicated small solid angle device. The physical design of the device and the small solid angle method were here in described, focus in particular on the analysis of detection efficiency, the effect of the isotope impurity in the coatings and the correction for the non-uniform distribution of the uranium samples. The results show that the weight of 235U in the coatings is 5.2-5.6 mg, while 4.7-5.0 mg for 238U and 2.2 mg for 236U in the corresponding coatings, with relative experimental uncertainties of 1.0%--1.2%.


Heat and moisture exchange capacity of the upper respiratory tract and the effect of tracheotomy breathing on endotracheal climate.
The aim of this study was to assess the heat and moisture exchange (HME) capacity of the upper respiratory tract and the effect of tracheotomy breathing on endotracheal climate in patients with head and neck cancer. We plotted the subglottic temperature and humidity measurements in 10 patients with head and neck cancer with a temporary precautionary tracheotomy during successive 10-minute periods of nose, mouth, and tracheotomy breathing in a randomized sequence. End-inspiratory temperatures of nose, mouth, and tracheotomy breathing were 31.1, 31.3, and 28.3°C, respectively. End-inspiratory humidity measurements of nose, mouth, and tracheotomy breathing were 29.3, 28.6, and 21.1 mgH₂O/L, respectively. There was a trend toward lower end-inspiratory humidity in patients with radiotherapy or with large surgery-induced oropharyngeal mucosal defects, whereas temperatures were similar. This study gives objective information about the HME capacity of the upper respiratory tract in patients with head and neck cancer with precautionary tracheotomy, and thus provides target values for HMEs for laryngectomized and tracheotomized patients.


Racial variation in umbilical cord blood sex steroid hormones and the insulin-like growth factor axis in African-American and white female neonates.
To evaluate whether there is racial variation in venous umbilical cord blood concentrations of sex steroid hormones and the insulin-like growth factor (IGF) axis between female African-American and white neonates. Maternal and birth characteristics and venous umbilical cord blood samples were collected from 77 African-American and 41 white full-term uncomplicated births at two urban hospitals in 2004 and 2005. Cord blood was measured for testosterone, dehydroespiandrosterone-sulfate, estradiol, and sex steroid hormone-binding globulin (SHBG) by immunoassay. IGF-1, IGF-2, and IGF-binding protein-3 (IGFBP-3) were measured by ELISA. Crude and multivariable-adjusted geometric mean concentrations were computed for the hormones. African-American neonates weighed less at birth (3,228 g vs. 3,424 g, p < 0.004) than whites. Birth weight was positively correlated with IGF-1, IGFBP-3, and the molar ratio of IGF-1 to IGFBP-3, but inversely correlated with the molar ratio of IGF-2 to IGFBP-3. Adjusted models showed higher testosterone (1.82 ng/ml vs. 1.47 ng/ml, p = 0.006) and the molar ratio of testosterone to SHBG (0.42 vs. 0.30, p = 0.03) in African-American compared to white female neonates. IGF-1, IGF-2, and IGFBP-3 were lower in African-American compared to white female neonates, but only the difference for IGF-2 remained significant (496.5 ng/ml vs. 539.2 ng/ml, p = 0.04). We provide evidence of racial variation in cord blood testosterone and testosterone to SHBG in African-American compared to white female neonates, and higher IGF-2 in white compared to African-American female neonates. Findings suggest plausible explanations for a prenatal influence on subsequent breast cancer risk and mortality. Further work is needed to confirm these observations.


A cross-sectional analysis of reported corporate environmental sustainability practices.
The concept of sustainability evolved throughout the 1970s and 1980s, but was formally described by the 27 principles of the Rio Declaration on Environment and Development in 1992. Despite the passage of nearly 20years, to date there are no uniform set of federal rules, regulations, or guidelines specifically governing the environmental aspects of sustainability practices or related requirements in the United States. In this benchmark analysis, we have collected information on the sustainability programs of the five largest US companies in each of the 26 industrial sectors [based on the Forbes Global 2000 through 2009 (n=130)]. For each company, we reviewed the most recent corporate sustainability, citizenship, or responsibility report, limiting our scope to environmental components, if available. Ten criteria were identified and analyzed, including leadership, reporting, external review, certification, and individual components of environmental sustainability programs. With respect to the prevalence of sustainability components between various business sectors, we found that the Drugs and Biotechnology (87%), Household and Personal Products (87%) and Oil and Gas Operations (87%) industries had the most comprehensive environmental sustainability programs. Using the nine components of environmental sustainability as a benchmark, we identified four key components as the characteristics of the most comprehensive environmental sustainability programs. These were (1) empowering leadership with a commitment to sustainability (80%), (2) standardized reporting (87%), (3) third-party evaluation of the sustainability programs (73%), and (4) obtaining ISO 14001 certification (73%). We found that many firms shaped their own definition of sustainability and developed their associated sustainability programs based on their sector, stakeholder interests, products or services, and business model. We noted an emerging area that we have called product sustainability - one in which toxicologists and environmental scientists can play a vital role helping to ensure that a manufactured item will indeed be considered acceptable for distribution now, as well as in the coming years. Numerous examples or case studies are presented.


Membrane repair of human skeletal muscle cells requires Annexin-A5.
Defect in membrane repair contributes to the development of limb girdle muscular dystrophy type 2B (LGMD2B) and Miyoshi myopathy. In healthy skeletal muscle, unraveling membrane repair mechanisms requires to establish an exhaustive list of the components of the resealing machinery. Here we show that human myotubes rendered deficient for Annexin-A5 (AnxA5) suffer from a severe defect in membrane resealing. This defect is rescued by the addition of recombinant AnxA5 while an AnxA5 mutant, which is unable to form 2D protein arrays, has no effect. Using correlative light and electron microscopy, we show that AnxA5 binds to the edges of the torn membrane, as early as a few seconds after sarcolemma injury, where it probably self-assembles into 2D arrays. In addition, we observed that membrane resealing is associated with the presence of a cluster of lipid vesicles at the wounded site. AnxA5 is present at the surface of these vesicles and may thus participate in plugging the cell membrane disruption. Finally, we show that AnxA5 behaves similarly in myotubes from a muscle cell line established from a patient suffering from LGMD2B, a myopathy due to dysferlin mutations, which indicates that trafficking of AnxA5 during sarcolemma damage is independent of the presence of dysferlin.


Granulocyte-colony-stimulating factor (G-CSF) signaling in spinal microglia drives visceral sensitization following colitis.
Pain is a main symptom of inflammatory diseases and often persists beyond clinical remission. Although we have a good understanding of the mechanisms of sensitization at the periphery during inflammation, little is known about the mediators that drive central sensitization. Recent reports have identified hematopoietic colony-stimulating factors as important regulators of tumor- and nerve injury-associated pain. Using a mouse model of colitis, we identify the proinflammatory cytokine granulocyte-colony-stimulating factor (G-CSF or Csf-3) as a key mediator of visceral sensitization. We report that G-CSF is specifically up-regulated in the thoracolumbar spinal cord of colitis-affected mice. Our results show that resident spinal microglia express the G-CSF receptor and that G-CSF signaling mediates microglial activation following colitis. Furthermore, healthy mice subjected to intrathecal injection of G-CSF exhibit pronounced visceral hypersensitivity, an effect that is abolished by microglial depletion. Mechanistically, we demonstrate that G-CSF injection increases Cathepsin S activity in spinal cord tissues. When cocultured with microglia BV-2 cells exposed to G-CSF, dorsal root ganglion (DRG) nociceptors become hyperexcitable. Blocking CX3CR1 or nitric oxide production during G-CSF treatment reduces excitability and G-CSF-induced visceral pain in vivo. Finally, administration of G-CSF-neutralizing antibody can prevent the establishment of persistent visceral pain postcolitis. Overall, our work uncovers a DRG neuron-microglia interaction that responds to G-CSF by engaging Cathepsin S-CX3CR1-inducible NOS signaling. This interaction represents a central step in visceral sensitization following colonic inflammation, thereby identifying spinal G-CSF as a target for treating chronic abdominal pain.


Time trends in distal colorectal cancer subsite location related to age and how it affects choice of screening modality.
A time trend analysis of colorectal cancer (CRC) incidence in the distal colorectum as a proportion of total CRC is presented for the period 1977-1994 as a function of age, to determine the age at which Americans might best be served by screening fiberoptic sigmoidoscopy. CRC incidence rates were obtained for each anatomic subsite from SEER Public Use Files for 1977, 1986, and 1994. The colorectum was divided anatomically for these analyses at the junction of the descending colon and sigmoid colon. Incidence in the distal colorectum was divided by total CRC incidence to determine the proportion of CRC in that age/race/gender/year cohort located in the distal colorectum. The proportion of distal CRC among African Americans was without a clear trend as they grew older in each of the years of observation and in both genders. However, in whites, with increasing age, the proportion of distal disease declined progressively in both genders, with the greatest decline in 1994. Distal CRC became less prevalent than proximal at about age 72 years in white women and at age 82 in white men in 1994. As the white population becomes older, and for African Americans of all ages, more total colon screening modalities are needed, although at the onset of recommended screening, among 50- to 60-year-olds, fiberoptic sigmoidoscopy would appear efficacious.


Structural and dynamical characterization of piroxicam by 1H- and 13C-NMR relaxation studies.
Carbon spin-lattice relaxation rates of an anti-inflammatory drug, piroxicam, have been measured. These results have been used in determining the reorientational rates of the proton carbon vectors. An analysis of internal motions within the pyridinyl moiety of piroxicam was carried out. Selective proton-carbon nuclear Overhauser effect (NOE) measurements were made in order to determine the solution structure of piroxicam. The effect of indirect NOE arising from exchangeable protons has been analyzed and considered.


Clinical evaluation of spatial accuracy of a fusion imaging technique combining previously acquired computed tomography and real-time ultrasound for imaging of liver metastases.
This study was designed to evaluate the spatial accuracy of matching volumetric computed tomography (CT) data of hepatic metastases with real-time ultrasound (US) using a fusion imaging system (VNav) according to different clinical settings. Twenty-four patients with one hepatic tumor identified on enhanced CT and US were prospectively enrolled. A set of three landmarks markers was chosen on CT and US for image registration. US and CT images were then superimposed using the fusion imaging display mode. The difference in spatial location between the tumor visible on the CT and the US on the overlay images (reviewer #1, comment #2) was measured in the lateral, anterior-posterior, and vertical axis. The maximum difference (Dmax) was evaluated for different predictive factors. CT performed 1-30 days before registration versus immediately before. Use of general anesthesia for CT and US versus no anesthesia. Anatomic landmarks versus landmarks that include at least one nonanatomic structure, such as a cyst or a calcification Overall, Dmax was 11.53 ± 8.38 mm. Dmax was 6.55 ± 7.31 mm with CT performed immediately before VNav versus 17.4 ± 5.18 with CT performed 1-30 days before (p < 0.0001). Dmax was 7.05 ± 6.95 under general anesthesia and 16.81 ± 6.77 without anesthesia (p < 0.0015). Landmarks including at least one nonanatomic structure increase Dmax of 5.2 mm (p < 0.0001). The lowest Dmax (1.9 ± 1.4 mm) was obtained when CT and VNav were performed under general anesthesia, one immediately after the other. VNav is accurate when adequate clinical setup is carefully selected. Only under these conditions (reviewer #2), liver tumors not identified on US can be accurately targeted for biopsy or radiofrequency ablation using fusion imaging.


Interaction of Citrus Juices with Cyclosporine: Systematic Review and Meta-Analysis.
Cyclosporine is an immunosuppressant with narrow therapeutic window, metabolized mainly by cytochrome P450 3A4 (CYP3A4) and minimally by cytochrome P450 3A5 (CYP3A5). Citrus juices such as grapefruit juice (GFJ), orange, lemon, pomelo and lime were known to interact with cyclosporine in several randomized controlled trials. The present review is a systematic compilation and quantitative synthesis on the changes of cyclosporine pharmacokinetics with concomitant citrus juice administration. Electronic databases were searched for randomized controlled trials evaluating the effect of any citrus juice on the pharmacokinetics of cyclosporine comparing with water or placebo in healthy volunteers using appropriate search strategies. Percent mean difference with standard error was used to assess the magnitude of difference in the following outcome measures: area under curve from time of drug administration to 24 h (AUC0-24), area under curve from time of drug administration to infinity (AUC0-∞), maximum concentration (C max), time to achieve C max (T max), elimination half-life (T 1/2), clearance (CL), volume of distribution and frequency for adverse drug reactions following administration of cyclosporine. RevMan 5.3 software was used to assess heterogeneity (by I2 statistics), use random-effects model and generate pooled results and Forest plot. A total of 57 studies were obtained with the search strategy, of which seven were found eligible to be included in the present review. The pooled percent mean difference [95 % CI] for GFJ in comparison to controls for AUC0-24, AUC0-∞, C max and T max of cyclosporine was observed to be 53 [43, 64], 53 [45, 62], 24 [12, 36] and 19 [12, 26], respectively. Similarly, pomelo juice was found to significantly increase both AUC0-∞ and C max with the pooled percent mean difference [95 % CI] as 23 [13, 32] and 25 [1, 50], respectively but decrease T 1/2 {-8 [-15, -1]} of cyclosporine. Orange juice did not alter any of the pharmacokinetic parameter of cyclosporine significantly. Citrus juices especially GFJ and pomelo juice were found to significantly increase the plasma exposure of cyclosporine while orange juice did not exhibit any significant interaction with cyclosporine.


Case report of a littoral cell angioma of the spleen and accessory spleens: A benign vascular tumour.
Littoral- cell angioma (LCA) is a rare benign vascular tumour of the spleen. There have been less then 80 cases reported in the literature. Recent reports have described it to be a malignant lesion with congenital and immunologic associations. We report a case of LCA of the spleen. A 52 -year-old male patient was admitted to hospital with a three month duration of intermittent upper abdominal pain and nausea. Imaging studies, including computer tomography (CT) and magnetic resonance imaging (MRI), showed multiple lesions in the spleen as well as in the accessory spleens. An open splenectomy was performed and his post-operative recovery was uneventful. Littoral cell angioma of the spleen is a benign vascular tumour that has been infrequently reported in the English literature. While it does have malignant potential, the vast majority are benign. Diagnosis depends on the expression of endothelial markers like CD31 and histiocytic markers like CD68.Malignant potential is enhanced by the presence of splenomegaly as well. This rare condition is made even more rare by the presence of the tumour in the two accessory spleens as well.


Sleep disturbances in subjects with autism spectrum disorder: A parental perspective.
To investigate the prevalence of sleep disturbances (SDs), their related comorbidities, interventions and the impact on the family for individuals with current SDs and those who had SDs in the past. Members of the Italian national association of parents of persons with autism (ANGSA) completed an anonymous online survey collecting demographic data, the presence of comorbidities and specific information on sleep arrangement and sleep disorders using a modified version of the of the Sleep Disturbance Scale for Children (SDSC). The final sample consisted of 143 participants, 90 patients presented current SDs (C_SDs) and 53 reported previous SDs (P_SDs). In the C_SDs group, the most prevalent sleep disorders were related to insomnia and, especially, difficulty falling asleep; a high number of individuals presented with restless sleep. Also, the parents in the P_SDs group retrospectively reported a high prevalence of insomnia with difficulty falling asleep, night awakenings and restless sleep. Parents reported that sleep hygiene practice were effective in less than one third of cases in both groups and the most used compound was immediate-release melatonin, followed by antihistamines and then benzodiazepines, antipsychotics, and antidepressants, with approximately 60-70% reported efficacy. Parents of both groups reported that insomnia negatively affected their children behavior and caused stress, mood changes or physical fatigue in their daily life. Our study shows that insomnia is most prevalent in individuals with autism with several consequences on children and family behavior and quality of life. As reported by parents, melatonin might be helpful for sleep disturbances in these children and the causes of restless sleep need further investigations.


TLR-mediated activation of type I IFN during antiviral immune responses: fighting the battle to win the war.
Toll-like receptors (TLRs) are crucially important in the sensing of viral infections and viral nucleic acids. TLR triggering leads to the induction of specific intracellular signaling cascades that result in the activation of two major families of transcription factors; the IFN-regulatory factors (IRFs) and nuclear factor-kappa B (NF-kappaB). IRFs and NF-kappaB work together to trigger the production of type I interferons (IFNalpha/beta) or inflammatory cytokines leading to the maturation of dendritic cells and the establishment of antiviral immunity. This review will focus on the most recent findings relating to the regulation of IRF activity by TLRs, highlighting the increasing complexity of TLR-mediated signaling pathways.


Involvement of Borrelia burgdorferi in cranial nerve affection.
From January 1984 to August 1985 54 patients presented with cranial nerve lesions at the neurological department of the University hospital Innsbruck. Median age was 42 years, range 5-81 years. Female male ratio was 49/15. In 17 patients cranial neuritis was consistent with meningopolyneuritis Bannwarth (MPN) in 37 cases mere facial palsy was present. Cranial neuritis in MPN-patients affected N. facilis in 10, N. opticus and N. oculo-motorius in one case each. Five patients had polyneuritis cranialis with affection of the cranial nerves II, V, VI, VII, VIII, and IX (Table 1). IgG-antibodies to B. burgdorferi were found in the sera of all MPN patients and in 15 of cases with mere facial palsy. Patients with antibodies to B. burgdorferi were treated with intravenous penicillin and latamoxef dinatrium. The remaining 22 patients were treated with vitamin B compound and corticosteroids. The time for full recovery was 4 weeks on the average in each treatment group.


Using spectrophotometry to determine in vitro turnover rates of peptides in plasma.
A new method for determination of first-order elimination constants for dipeptides is presented. The peptides are hydrolysed by plasma enzymes into amino acids, and ortho-phthaldialdehyde (OPA) is used to react with free primary amino groups. The concentration of free amino groups can, thus, be followed using simple spectrophotometry. A mathematical model for the concentration of free primary amino groups with time is presented through which the elimination constant, and thus the half life, can be determined by curve fitting. The method is applied to inhibitors of angiotensin-converting enzyme derived from the primary structure of milk proteins. The results show that these dipeptides have in vitro half lives ranging from 4.3-64 min, when incubated with 50% rat plasma. This explains why these casokinins in vivo only cause a very moderate and short-lasting inhibition. The model for calculation of elimination constant is limited to dipeptides that do not contain a C-terminal proline. The derivatization method can be applied to longer peptides as a crude indicator of peptide hydrolysis, but does not allow calculation of their elimination constants per se.


Epidemiologic typing of methicillin-resistant Staphylococcus aureus in neonate intensive care units using pulsed-field gel electrophoresis.
To elucidate the mode of dissemination of methicillin-resistant Staphylococcus aureus (MRSA) in neonate intensive care units (NICUs), a total of 223 isolates from 3 separate hospitals were investigated between 1994 and 1996 by a DNA fingerprinting technique with pulsed-field gel electrophoresis (PFGE). Exoprotein profiles of some strains were also examined using SDS-polyacrylamide gel-electrophoresis (SDS-PAGE) and the assessment of enzyme/toxin production such as coagulase, enterotoxin and TSST-1. Judging from the strain typing data from PFGE results and the epidemiological data, 2 different types of PFGE patterns (A and B) and their subtypes (A', A'' and B') were identified. The A type including A' and A'' (comprising approximately 95% of the isolates) was markedly dominant. Only 5% of the isolates belonged to type B and subtype B'. On the other hand, MRSA isolated from adult patients admitted to the same hospital showed many different PFGE patterns. The results strongly suggested that some strain(s) with specific PFGE pattern(s) is prevalent in NICUs. Furthermore, isolates which expressed the same PFGE pattern did not always express the same SDS-PAGE pattern. There were some isolates with different abilities to produce coagulase, enterotoxin C and toxic-shock syndrome toxin (TSST)-1, and the abilities had no relation with a particular type of PFGE pattern. Therefore, a combination of PFGE analysis and biochemical analyses of coagulase, enterotoxin C and TSST-1 may provide us with more detailed information for the epidemiological study of MRSA in NICUs.


Hyoid and laryngeal chondrosarcomas have different clinicopathologic features.
Hyoid chondrosarcomas (CSs) are uncommon cervical tumours with different features compared to laryngeal CSs. Herein we report a hyoid CS in a 36-year-old male and review the literature. Only eight cases of hyoid CS have been reported to date. We have found important differences between hyoid and laryngeal CSs in terms of the age at presentation, gender, clinical symptoms, time before diagnosis, histologic findings and tumour size.


Multiple cranial nerve palsies complicating retrobulbar eye block.
This report details a case of accidental brainstem anaesthesia complicating retrobulbar block for cataract surgery in an 83-year-old man. Prompt diagnosis and treatment resulted in a successful outcome. The many possible presentations of brainstem anaesthesia are described and causative mechanisms are discussed.


A Phase I Study of Abiraterone Acetate Combined with BEZ235, a Dual PI3K/mTOR Inhibitor, in Metastatic Castration Resistant Prostate Cancer.
The combination of standard dose abiraterone acetate and BEZ235, a pan-class I PI3K and mTORC1/2 inhibitor, was poorly tolerated in men with progressive mCRPC.Although the clinical development of BEZ235 has been discontinued in prostate cancer, agents that more selectively target PI3K-AKT-mTOR signaling may have a more favorable therapeutic index and should continue to be explored. Androgen receptor (AR) and phosphatidylinositol-3 kinase (PI3K) signaling are two commonly perturbed pathways in prostate cancer. Preclinical data have shown that the two pathways compensate for each other when one is inhibited, and combined inhibition of AR and PI3K signaling may be a viable strategy to prevent or overcome castration resistance. This phase I study evaluated the safety and tolerability of abiraterone acetate and prednisone combined with BEZ235, a dual PI3K and mTORC1/2 inhibitor, in men with progressive metastatic castration resistant prostate cancer (mCRPC) who have not received prior chemotherapy. Six patients (n = 6) were treated at the starting dose level of abiraterone acetate 1,000 mg with prednisone 5 mg twice daily and BEZ235 200 mg twice daily in a 3 + 3 dose escalation design. The study was terminated early because three of the six patients (50%) experienced dose-limiting toxicities: grade 3 mucositis, grade 3 hypotension, and grade 4 dyspnea and pneumonitis. All six patients had previously progressed on abiraterone/prednisone. The median treatment duration was 27 days (range: 3-130 days). No prostate-specific antigen (PSA) decline or objective response were observed. The combination of standard-dose abiraterone/prednisone with BEZ235 200 mg twice daily was poorly tolerated in patients with mCRPC. The on-target and off-target effects of dual PI3K and mTORC inhibition likely contributed to the unacceptable toxicity profile. The Oncologist 2017;22:503-e43.


Selective adsorption and separation of chromium (VI) on the magnetic iron-nickel oxide from waste nickel liquid.
The selective adsorption of Cr (VI) from the wastewater of Cr (VI)-Ni (II) by magnetically iron-nickel oxide was investigated in this study. Synthetic iron-nickel oxide magnetic particles in the co-sedimentation method were used as adsorbent to remove hexavalent chromium ions. The characteristic of adsorption was evaluated by Langmuir, Freundlich isotherm and Dubinin-Kaganer-Radushkevich (DKR) equations in the simulation wastewater of Cr (VI)-Ni (II) bi-system. The energy spectra and FT-IR analysis were used to test adsorbent before and after adsorption. The obtained results suggest that the uptake of chromium (VI) effect is obvious from phosphate anions and that from others is unobvious. The maximum adsorption capacity of hexavalent chromium is about 30 mg/g at pH 5.00+/-0.02, and it was reduced by increasing the total dissolved substance (TDS) of system. Adsorption energies E are about 10.310-21.321 kJ/mol which were obtained from DKR equation in difference TDS conditions. The regeneration shows that the iron-nickel oxide has good reuse performance and the hexavalent chromium was recycled. The major adsorption mechanism proposed was the ions exchange; however the surface coordination was a main role in the condition of TDS less than 200mg/L.


Influence of the chemical composition on gamma ray attenuation by fatty acids.
The dependence of gamma ray attenuation on the chemical composition of fatty acids is investigated in the energy range from 10(-3) to 10(5) MeV. The mass attenuation coefficients (muF) and effective atomic numbers (Zeff) have been calculated for 27 different fatty acids. They show appreciable variation with the chemical composition of fatty acids in the region of gamma ray energies from 10(-3) to 10(5) MeV.


Estradiol valerate/dienogest.
Estradiol valerate 2mg/dienogest 2mg is an oral estrogen/ progestogen formulation that has been approved throughout the European Union for the treatment of climacteric symptoms in postmenopausal women. Dienogest is a progestogen that combines the properties of both progesterone and 19-nortestosterone derivatives. It has moderate affinity for the progesterone receptor, significant antiproliferative and antiandrogenic activity, and produces secretory transformation of the endometrium. Estradiol valerate is an esterified form of natural 17beta-estradiol, the most potent endogenous human ovarian estrogen, and is hydrolysed to estradiol soon after oral administration. Results from a randomised, double-blind, multicentre trial showed that oral estradiol valerate 2mg/dienogest 2mg and estradiol valerate 2mg/dienogest 3mg once daily for 1 year were each as effective as estradiol 2mg/estriol 1mg/norethisterone acetate 1mg in the treatment of climacteric symptoms in 581 postmenopausal women; reductions from baseline in Kupperman Index scores were 78.5, 74.5 and 75.0%, respectively. The number of days without any type of bleeding was lowest in patients treated with estradiol valerate 2mg/dienogest 2mg (8.7 days), and highest in the estradiol valerate 2mg/ dienogest 3mg group (12.1 days). During the twelfth month of treatment with estradiol valerate 2mg/dienogest 2mg, the percentage of patients who reported bleeding was 14.5%. Endometrial biopsy results were similar in patients treated with estradiol valerate 2mg/dienogest 2mg, estradiol valerate 2mg/dienogest 3mg or estradiol 2mg/estriol 1mg/norethisterone acetate 1mg once daily for 1 year; 90.8, 87.4 and 87.5% of samples, respectively, contained atrophic material. Proliferative material was found in 4.2, 2.5 and 4.4% of the biopsies, respectively; there was no incidence of hyperplasia in any of the treatment groups. A noncomparative multicentre study in 1501 postmenopausal women demonstrated that adverse events associated with estradiol valerate 2mg/dienogest 2mg once daily for 48 weeks included breakthrough bleeding, mastalgia, headache, abdominal pain, hypertension, thrush, migraine, weight gain, increase in endometrial thickness and metrorrhagia.


[Electric stimulation acupuncture in peripheral neuropathic pain syndromes. Clinical pilot study on analgesic effectiveness].
The aim of this pilot study was to investigate the potential value of acupuncture in the treatment of peripheral neuropathic pain. Explorative analysis should provide data for further randomised controlled trials. In an uncontrolled clinical trial electroacupuncture was given to 17 patients with chronic neuropathic pain of peripheral origin which was resistant to preceding pain therapy. Patients were treated twice weekly for 4 weeks. Assessment of outcome measurements comprised: Intensity of continuous pain (visual analogue scale, VAS), intensity of pain attacks (VAS), duration of pain attacks, number of pain attacks and changes in mood (VAS). All measures were evaluated by diary (1 week before treatment to 2 weeks after treatment and 1 week at follow up three months after treatment). Changes of global complaints and patients' beliefs in treatment (credibility assessment) were also assessed. At re-evaluation two weeks after treatment, mean continuous pain was reduced by 32.9% and intensity of pain attacks was reduced by 59%. Mean number of daily pain attacks decreased from 4.2 (SD +/- 4.6, 0.14-13.3) before treatment to 2.2 (SD +/- 3.8, 0-7.5) two weeks after treatment. Duration of pain attacks and mood showed no substantial changes. Three months after treatment, continuous pain was reduced by 15.9% and intensity of pain attacks was reduced by 44% compared to baseline. No serious adverse events were observed On the basis of this small pilot study, trial treatment by electroacupuncture seems to be justified in these patients given a lack of success of standard treatments. The apparent beneficial analgesic effects of electroacupuncture appear to warrant further investigation.


[From anamnesis to the art of interpretation, or: What is a "genuine" psychoanalyst? Wolfgang Warda, Ludwig Binswanger, Wilhelm Strohmayer and the origins of psychoanalysis in Thuringia].
Warda and Strohmayer from Thuringia were among the first German physicians who developed an interest in Freuds theory and therapeutic method around 1900. Their contributions reflect the influence of Otto Binswanger, professor of psychiatry in Jena, a representative of the "psychological direction" in psychiatry which in the beginning was relatively receptive to Freud. The paper discusses their rapprochement to, and detachment from, the Freudian school, including also the work of a third young physician: Ludwig Binswanger, Otto's nephew, who was active in Jena at the same time. It points to certain factors contributing to the increasing rejection Freud met in academic circles which have been underrated to date: (1) the transformation of psychoanalysis into an art of interpretation; (2) the introduction of transference. Both factors which were elaborated by Freud as essentials of his theoretical and practical approach around 1900 and published in 1904/05, undermined the claim of academic medicine to objectivity. The paper describes how psychoanalysis officially abandoned the scientific standards of contemporary medicine at the Weimar congress in 1911, at the same time as Warda and Strohmayer left the Freudian group.


The existence of a nonclassical TCA cycle in the nucleus that wires the metabolic-epigenetic circuitry.
The scope and variety of the metabolic intermediates from the mitochondrial tricarboxylic acid (TCA) cycle that are engaged in epigenetic regulation of the chromatin function in the nucleus raise an outstanding question about how timely and precise supply/consumption of these metabolites is achieved in the nucleus. We report here the identification of a nonclassical TCA cycle in the nucleus (nTCA cycle). We found that all the TCA cycle-associated enzymes including citrate synthase (CS), aconitase 2 (ACO2), isocitrate dehydrogenase 3 (IDH3), oxoglutarate dehydrogenase (OGDH), succinyl-CoA synthetase (SCS), fumarate hydratase (FH), and malate dehydrogenase 2 (MDH2), except for succinate dehydrogenase (SDH), a component of electron transport chain for generating ATP, exist in the nucleus. We showed that these nuclear enzymes catalyze an incomplete TCA cycle similar to that found in cyanobacteria. We propose that the nTCA cycle is implemented mainly to generate/consume metabolic intermediates, not for energy production. We demonstrated that the nTCA cycle is intrinsically linked to chromatin dynamics and transcription regulation. Together, our study uncovers the existence of a nonclassical TCA cycle in the nucleus that links the metabolic pathway to epigenetic regulation.


Prognostic value of plasma catecholamines, plasma renin activity, and plasma atrial natriuretic peptide at rest and during exercise in congestive heart failure: comparison with clinical evaluation, ejection fraction, and exercise capacity.
Survival in congestive heart failure is related to plasma catecholamines and atrial natriuretic peptide at rest, but the prognostic importance of changes during exercise is unknown. The aim of this study was to evaluate the prognostic value of catecholamines and atrial natriuretic peptide at rest and during maximal exercise in congestive heart failure, and to compare it to clinical and exercise test variables and left ventricular ejection fraction. One hundred ninety consecutive patients (136 men and 54 women; median age, 66 years; range, 42-75 years) with clinically stable congestive heart failure were included. Sixteen patients were in New York Heart Association class I, 87 in class II, 83 in class III, and 4 in class IV. Left ventricular ejection fraction was 0.30 (range, 0.06-0.74). Total survival after 1 year was 79%, after 2 years, it was 68%. Prognostic variables at univariate analysis were: plasma noradrenaline at rest (P < .0001), plasma adrenaline at rest (P = .049), and atrial natriuretic peptide at rest (P = .016). During exercise, plasma catecholamines and plasma atrial natriuretic peptide increased significantly; the change, however, was not related to survival. Six variables carried significant, independent prognostic information in a multivariate analysis: left ventricular ejection fraction (P = .03), plasma noradrenaline at rest (P = .009), New York Heart Association class III + IV (P = .005), increase in heart rate during exercise < or = 35 min-1 (P < .0001), serum creatinine > 121 mumol/L (P = .004), and serum urea > 7.6 mmol/L (P = .007). Patients with congestive heart failure have a poor survival despite intensive medical treatment. Plasma catecholamines and plasma atrial natriuretic peptide are elevated at rest and rises further during exercise; the increase, however, is not related to mortality. Plasma noradrenaline at rest contributes with further prognostic information despite knowledge of clinical and exercise variables and was the only neurohormonal variable with independent, significant prognostic information on survival.


Moderate hemophilia B Leyden: identification by polymerase chain reaction, sequencing, and oligomer restriction.
Hemophilia B Leyden is a rare form of congenital factor IX deficiency which is characterized by severe factor IX deficiency at birth, which ameliorates after puberty. It is caused by mutations in the factor IX gene promoter region and the postpubertal amelioration is thought to be mediated by the action of testosterone on an androgen response element located in the promoter region. Three kindreds have been previously reported with a milder form of hemophilia B Leyden, associated with a guanine to adenine transition at nucleotide position -6 of the promoter region. We now report a fourth kindred with this mutation. The proband was a newborn with a factor IX level of 2.5%, his 12-year-old half-brother had a level of 28%, and his mother's 56-year-old maternal cousin had a level of 60%. A G to A transition at nucleotide -6 of the promoter region was demonstrated by cloning and sequencing polymerase chain reaction products from the half brother, and the mother was demonstrated to be a carrier. The mutation eliminates a TaqI restriction endonuclease site normally present in the wild type promoter, and the mother's cousin was demonstrated to carry the mutation by the absence of digestion with TaqI. The identification of hemophilia B Leyden with this specific mutation has practical importance to the clinical management because of its unique natural history and significantly better prognosis than classical hemophilia B.


Sohlh2 knockout mice are male-sterile because of degeneration of differentiating type A spermatogonia.
The spermatogenesis and oogenesis-specific transcription factor Sohlh2 is normally expressed only in premeiotic germ cells. In this study, Sohlh2 and several other germ cell transcripts were found to be induced in mouse embryonic stem cells when cultured on a feeder cell line that overexpresses bone morphogenetic protein 4. To study the function of Sohlh2 in germ cells, we generated mice harboring null alleles of Sohlh2. Male Sohlh2-deficient mice were infertile because of a block in spermatogenesis. Although normal prior to birth, Sohlh2-null mice had reduced numbers of intermediate and type B spermatogonia by postnatal day 7. By day 10, development to the preleptotene spermatocyte stage was severely disrupted, rendering seminiferous tubules with only Sertoli cells, undifferentiated spermatogonia, and degenerating colonies of differentiating spermatogonia. Degenerating cells resembled type A2 spermatogonia and accumulated in M-phase prior to death. A similar phenotype was observed in Sohlh2-null mice on postnatal days 14, 21, 35, 49, 68, and 151. In adult Sohlh2-mutant mice, the ratio of undifferentiated type A spermatogonia (DAZL+/PLZF+) to differentiating type A spermatogonia (DAZL+/PLZF-) was twice normal levels. In culture, undifferentiated type A spermatogonia isolated from Sohlh2-null mice proliferated normally but linked the mutant phenotype to aberrant cell surface expression of the receptor-tyrosine kinase cKit. Thus, Sohlh2 is required for progression of differentiating type A spermatogonia into type B spermatogonia. One conclusion originating from these studies would be that testicular factors normally regulate the viability of differentiating spermatogonia by signaling through Sohlh2. This regulation would provide a crucial checkpoint to optimize the numbers of spermatocytes entering meiosis during each cycle of spermatogenesis. Disclosure of potential conflicts of interest is found at the end of this article.


Pharmacological characterization of the algesic response to the subplantar injection of serotonin in the rat.
Subplantar injection of 0.10 micrograms of serotonin in the rat resulted in a brief period (0-20 min) of increased pain sensitivity to an applied force (hyperalgesia) which preceded a longer period (40-120 min) of decreased pain sensitivity (hypoalgesia). The magnitude of each of these changes and the duration of the hypoalgesia were dose-dependent. The development of hyperalgesia was selectively and dose dependently reduced by inhibitors of arachidonate cyclooxygenase. The hypoalgesia was selectively and dose dependently reduced by the serotonin antagonist methysergide. Selective inhibition of the hyperalgesia by aspirin and of the hypoalgesia by methysergide revealed that components of both hyperalgesia and hypoalgesia were present in the 10-120 min interval. These findings, the level of serotonin reported to be released in rat dermal tissue, and selective drug inhibition studies suggest that some irritant-induced changes in algesia measured in the rat hindlimb result from release of dermal stores of serotonin. Selective inhibition of the hypoalgesic component of the hindlimb irritant trypsin by the antiserotonin agent methysergide supports this hypothesis. The principal conclusion derived from these studies is that the algesic response to the subplantar injection of a single agent can be the resultant of independent, temporally overlapping hyperalgesic and hypoalgesic components each of different intensity and pharmacological sensitivity.


The quinolones. An overview of their pharmacology.
The fluoroquinolones represent a relatively new class of antibiotics with outstanding therapeutic potential, attributable to their broad spectrum of antimicrobial activity and favourable tissue distribution. They are highly active against most Gram-negative pathogens, as well as Staphylococcus aureus and coagulase-negative staphylococci. In addition, the fluoroquinolones have useful pharmacokinetic properties: they are orally active, and their lipophilicity and low degree of plasma protein binding allow for excellent tissue penetration and concentrations, as reflected in their particularly large apparent volumes of distribution. Infections due to aerobic Gram-negative pathogens are considered those most susceptible to the quinolones. Disease indications in which these agents appear to offer the greatest therapeutic advantage over currently available alternatives include the following: complicated urinary tract infections (particularly those caused by Pseudomonas aeruginosa or resistant Gram-negative microorganisms); suspected bacterial gastroenteritis; eradication of Salmonella typhi from the faeces in known carriers; P. aeruginosa-associated respiratory exacerbation in patients with cystic fibrosis; and chronic Gram-negative bacterial osteomyelitis. Direct comparisons of the various quinolones are too limited to date to provide clear therapeutic options. Nevertheless, this class of compounds is likely to play a major role in providing effective oral therapy for conditions that have previously required prolonged parenteral treatment.


Oxygen free radical mediated renal dysfunction.
Postischemic renal dysfunction (PIRD) is characterized by a reduction in glomerular filtration and tubular reabsorption of solute. The relative contribution of oxygen free radicals (OFRs) generated during reperfusion remains unclear. This study characterized the renal response to OFRs--independent of an ischemic insult. Isolated rat kidneys were perfused at 37 degrees C and 90-100 mm Hg with a modified Krebs' buffer. Hypoxanthine (25 mumole) and xanthine oxidase (1 unit) were combined and infused proximal to the kidney. There was a 50% increase in vascular resistance. This was accompanied by a 30% reduction in perfusate flow rate and a 70% reduction in glomerular filtration rate. There was also a significant reduction in urine flow rate and oxygen consumption. The percentage reabsorption of filtered water and sodium by the renal tubules was not diminished, however. This pattern was not observed when the xanthine oxidase was inactivated or when the perfusate was pretreated with superoxide dismutase (250 units/ml) and catalase (500 units/ml). The generation of OFRs, independent of an ischemic insult, causes a decrease in glomerular filtration out of proportion to the decrease in renal flow similar to that observed with PIRD. OFRs may contribute to the hemodynamic and glomerular alterations seen with PIRD. Factors other than OFRs, probably associated with ischemia, must be responsible for the tubular dysfunction.


Carbonic anhydrase inhibitors: design of thioureido sulfonamides with potent isozyme II and XII inhibitory properties and intraocular pressure lowering activity in a rabbit model of glaucoma.
A new series of thioureido-substituted sulfonamides were prepared by reacting 4-isothiocyanato- or 4-isothiocyanatoethyl-benzenesulfonamide with amines, hydrazines, or amino acids bearing moieties that can lead to an enhanced hydrosolubility, such as 2-dimethylamino-ethylamine, fluorine-containing aromatic amines/hydrazines, an aminodiol, heterocyclic polyamines (derivatives of morpholine and piperazine), 4-aminobenzoic acid, or natural amino acids (Gly, Cys, Asn, Arg, and Phe). The new compounds showed good inhibitory properties against three physiologically relevant carbonic anhydrase (CA, EC 126.96.36.199) isozymes, with K(I)s in the range of 24-324 nM against the cytosolic isoform CA I, of 6-185 nM against the other cytosolic isozyme CA II, and of 1.5-144 nM against the transmembrane isozyme CA XII. Some of the new derivatives were also very effective in reducing elevated intraocular pressure in hypertensive rabbits as a glaucoma animal model. Considering that this is the first study in which potent CA II/CA XII inhibitors are designed and investigated in vivo, it may be assumed that the target isozymes of the antiglaucoma sulfonamides are indeed the cytosolic CA II and the transmembrane CA XII.


Thrombospondin Mutations and Patients With Primary Congenital Glaucoma in a United States Population.
Mutations in the thrombospondin 1 ( THBS1 ) gene have been previously reported in primary congenital glaucoma (PCG) pedigrees that exhibit autosomal dominant inheritance with low penetrance. We sought to determine the role of THBS1 mutations in a cohort of 20 patients with PCG and 362 normal controls from Iowa using a combination of Sanger sequencing and whole exome sequencing. We detected 16 different THBS1 variants, including 4 rare, nonsynonymous variants (p.Thr611Met, p.Asn708Lys, p.Gln1089His, and p.Glu1166Lys). However, none of these variants were judged to be disease-causing mutations based on: 1) prevalence in cases and controls from Iowa, 2) prevalence in the public database gnomAD, 3) mutation analysis algorithms, and 4) THBS1 DNA sequence conservation. These results indicate THBS1 mutations are not a common cause of PCG in patients from Iowa and may be a rare cause of PCG overall.


Response to commentators of "a critique of positive responsibility".
It has been claimed that (1) computer professionals should be held responsible for an undisclosed list of "undesirable events" associated with their work and (2) most if not all computer disasters can be avoided by truly understanding responsibility. Commentators of "A Critique of Positive Responsibility in Computing" argue that this is not Donald Gotterbarn's view (Gotterbarn, JSEE 14(2):235-239, 2008) but that a critique of the view nevertheless raises significant moral issues within computing such as the ethical goals of a computing profession, the appropriate ethical stance toward bugs, and the public good with respect to computing (Miller, JSEE 14(2):245-249, 2008). Commentators also argue that "A Critique"'s "profitable misreading" demonstrates the "moral ecology" of organizations "dedicated narrowly to financial success" and that other "moral ecologies" that are customer or quality driven can be shown to be more important or preeminent (Huff, JSEE 14(2):241-244, 2008). It is argued here that (1) the hyper-inflated reading of Gotterbarn's and Ladd's views on positive responsibility persists despite Gotterbarn's explicit rejection of it, and that (2) such a reading of positive responsibility cannot be placed within a single moral ecology, nor can a single moral ecology be shown to be any more important or preeminent than others.


Studies on the regulation of RNA synthesis in neuronal and glial nuclei isolated from rat brain.
In searching for regulatory mechanisms involved in the cell-specific neuronal and glial transcription a cell-free transcriptional system has been developed using neuronal and glial rat brain chromatin and partially purified neuronal and glial nuclear rat brain RNA polymerases. Both free and chromatin-bound (engaged) neuronal and glial RNA polymerase fractions were separated from isolated neuronal and glial rat brain nuclei to determine their transcriptive efficiency. A double number of RNA initiation sites was measured on the neuronal when compared to the glial chromatin, independently of whether the neuronal or the glial RNA polymerase preparation was used for the determination. Structural modification of the neuronal and glial chromatin template by acetylation with acetyl-coenzyme A leads to an increase of the total number of RNA initiation sites available for exogenously added rat brain RNA polymerase. This indicates that acetylation of chromatin-bound proteins is capable to render primarily restricted gene sequences transcriptable. A positive correlation exists between the extent of acetate uptake by neuronal and glial chromatin-bound histone fractions and the extent of the increase of the number of RNA initiation sites is specifically related to histone acetylation rather than to acetylation of any other chromatin protein. Significant information in this respect could be achieved by dissociation of chromatin into its principal components and selectively reconstituting DNA with specifically acetylated histone and non-histone proteins.


REM and delta sleep in anorexia nervosa and bulimia.
Several recent investigations have suggested that neurobiological similarities may exist between patients with eating disorders and those with depression. We performed polysomnograms for two consecutive nights on nine bulimic and six anorectic patients who had no concomitant diagnosis of endogenous depression. The rapid eye movement (REM) latency, REM density, and delta sleep of these subjects on night 2 were compared to those of 10 healthy controls of similar ages. Contrary to reports of shortened REM latency and increased REM density in depressed patients, we did not find significant REM differences between eating disorder patients without endogenous depression and healthy control subjects. Low weight anorectics did appear to have less delta sleep than did controls. These findings do not support the contention that eating disorders are variants of affective disorders.


Fluorescently-labelled amyloid paired helical filaments (PHF) in monitoring its fibrillation kinetics.
The core of the tau fibrils in Alzheimer disease is a hexapeptide sequence organized in paired helical filaments (PHF). This sequence AcPHF6 can be used as tau fibrils model for the fast screening of potential therapeutic inhibitors of fibril formation or their disruption. The assay is usually performed by monitoring the fluorescence increase of Thioflavin T (ThT), well-known reporter dye for fibrillation. However, the ThT assay is not faultless, and here we present novel fluorescent dye, cyanine attached to amino acid side-chain (Cy-aa) that shows several advantages over ThT. The fibrillation kinetics of AcPHF6 was monitored via Cy-aa at twenty times lower concentration compared to ThT and successfully reported the presence of fibrillation inhibitor by Cy-aa fluorescence decrease. Additionally, spectral properties of Cy-aa are red-shifted in comparison to ThT allowing screening of a wider range of potential fibrillation inhibitors. Moreover, in the mixture with the pre-formed fibrils, Cy-aa shows strong fluorescence light-up proportional to fibrils concentration. We also successfully coupled this fluorescent amino acid to PHF in order to completely avoid the possibility of dye displacement with screening compound, and this newly designed conjugate showed to be a reliable intrinsic fluorescent probe for monitoring fibrillation kinetics of amyloid peptides.


Hexose transport by brain slices: further studies on energy dependence.
We studied the uptake of [3H]2-deoxyglucose [( 3H]2DG) by slices of rat cerebral cortex in vitro as a model of glucose transport by brain. Slices were incubated with [3H]2DG, or with L-[3H]glucose as a marker for diffusion; the difference between [3H]2DG uptake and L-[3H]glucose uptake was defined as net [3H]2DG transport. Net [3H]2DG transport was a function of incubation temperature, with an estimated temperature coefficient of 1.87 from 15 degrees C to 25 degrees C. The net uptake of [3H]2DG was not inhibited by phlorizin or phloretin in concentrations well above the reported Ki of these inhibitors for hexose uptake in other systems. To examine the hypothesis that [3H]2DG transport by brain slices is dependent on mitochondrial energy, we studied net [3H]2DG uptake by slices which had been preincubated in media designed to alter intracellular ATP stores. The transport process was very sensitive to inhibition by DNP, but the correlation between [3H]2DG transport and ATP levels was unclear. In contrast to our published hypothesis that the transport process required mitochondrial energy, these data indicate that dependence on energy is not absolute.


"The One Who Guides" Nigral Neuron Migration.
In this issue, Brignani, Raj, et al. show that Netrin-1 from distinct sources controls neuronal migrations into the substantia nigra. Remarkably, one source of Netrin -1 is forebrain axons traversing the midbrain, and this is required for proper GABAergic neuronal migration into the substantia nigra pars reticulata.


Correction to: Expression of B7-H6 expression in human hepatocellular carcinoma and its clinical significance.
[This corrects the article DOI: 10.1186/s12935-018-0627-7.].


Rat glomerular epithelial cells produce and bear factor H on their surface that is up-regulated under complement attack.
Factor H is a potent complement inhibitory molecule that is primarily produced by the liver and appears in plasma as a soluble protein. Yet there is evidence that other cells, including those in the kidney, can produce factor H, and that it can be cell-associated as well as present as a plasma protein. Here we studied factor H in rat glomerular epithelial cells (GEC). A polyclonal antibody to factor H was used to identify factor H protein. A polymerase chain reaction (PCR)-based strategy was utilized to clone the full-length cDNA of GEC factor H. The relative quantity of factor H mRNA was measured by quantitative reverse transcription (RT)-PCR in cultured GEC exposed to complement activation and in the passive Heymann nephritis (PHN) model of membranous nephropathy. By immunofluorescence microscopy, factor H protein was present on the plasma membranes of cultured GEC. Based upon Western blot studies, this appeared to be the full-length 150 kD factor H protein. Factor H cDNA cloned from GEC was identical to the newly deposited sequence for rat liver factor H cDNA. In cultured GEC in which complement was activated, factor H mRNA increased over time. Similarly, in the PHN model in which complement was activated on GEC in vivo, factor H mRNA and protein also increased over time. Cultured GEC and glomeruli express factor H mRNA and protein. As modeled both in vitro and in vivo in the rat, factor H is up-regulated in membranous nephropathy. This is likely to be a direct response of GEC to complement attack and may represent a protective response of this cell.


Minimal enteral nutrition.
Although parenteral nutrition has been used widely in the management of sick very low birth weight (VLBW) infants, a smooth transition to the enteral route is most desirable. Animal studies have shown that long periods of starvation are associated with mucosal atrophy and reduction of enzymatic activity. Studies have shown that giving small volumes of feeds frequently exerts a trophic effect on the gut mucosa. This concept has been termed as Minimal Enteral Nutriton (MEN). Clinical benefits of MEN include faster progression to full enteral feeds, lesser episodes of feed intolerance and reduction in hospital stay without a concomitant increase in the risk of necrotizing enterocolitis. MEN may be commenced in neonates on ventilation and total parenteral nutrition. A protocol for giving MEN has been described.


Tuberculous pericarditis: long-term outcome in patients who received medical therapy alone.
A conservative approach to operative intervention in the treatment of active tuberculous pericarditis was adopted and only 4 of 16 consecutive patients underwent pericardiectomy, all within 2 months of diagnosis. One patient died of constrictive pericarditis despite pericardiectomy, and one died of acute bronchopneumonia after 8 months of otherwise successful medical management. All 14 long-term survivors were reevaluated to exclude chronic constrictive pericarditis and other potential sequelae of tuberculous pericarditis. Reevaluation included physical examination, chest radiograph, electrocardiogram, M-mode and two-dimensional echocardiogram, computed tomography (CT) scan, and in patients less than or equal to 75 years of age, incremental cycle exercise to maximum oxygen consumption. None were found to have chronic constrictive pericarditis or convincing evidence of other recognized complications of tuberculous pericarditis. Our results suggest that when pericardiectomy is not required for the relief of cardiac compression during the acute phase of tuberculous pericarditis and patients are treated with medical therapy alone, an excellent long-term outcome may be anticipated.


Deficiency of interleukin-6 receptor ameliorates PM2.5 exposure-induced pulmonary dysfunction and inflammation but not abnormalities in glucose homeostasis.
Ambient fine particulate matter (PM2.5) exposure increases local and systemic interleukin-6 (IL-6). However, the pathogenic role of IL-6 signalling following PM2.5 exposure, particularly in the development of pulmonary dysfunction and abnormal glucose homeostasis, has hardly been investigated. In the study, IL-6 receptor (IL-6R)-deficient (IL-6R-/-) and wildtype littermate (IL-6R+/+) mice were exposed to concentrated ambient PM2.5 (CAP) or filtered air (FA), and their pulmonary and metabolic responses to these exposures were analyzed. Our results demonstrated that IL-6R deficiency markedly alleviated PM2.5 exposure-induced increases in lung inflammatory markers including the inflammation score of histological analysis, the number of macrophages in bronchoalveolar lavage fluid (BALF), and mRNA expressions of TNFα, IL-1β and IL-6 and abnormalities in lung function test. However, IL-6R deficiency did not reduce the hepatic insulin resistance nor systemic glucose intolerance and insulin resistance induced by PM2.5 exposure. Our findings support the crucial role of IL-6 signalling in the development of pulmonary inflammation and dysfunction due to PM2.5 exposure but question the putative central role of pulmonary inflammation for the extra-pulmonary dysfunctions following PM2.5 exposure, providing a deep mechanistic insight into the pathogenesis caused by PM2.5 exposure.


Isolation and identification of three potential impurities of pholcodine bulk drug substance.
Three previously unreported manufacturing impurities were isolated from a pholcodine mother liquor using preparative reversed-phase HPLC. The liquor was the residue remaining after recrystallisation of a production batch of pholcodine. The impurities, which are structurally related to pholcodine, were initially detected by thin-layer chromatography (TLC). Their structures were determined after separation by preparative HPLC (Econo-Prep 5 microm C18 column, 30 cm x 21.2 mm i.d.). Structure elucidation was carried out using nuclear magnetic resonance (NMR) spectroscopy, mass spectroscopy (MS) and ultra violet (UV) spectroscopy. The impurities were identified as alkylated derivatives of pholcodine possessing second 2-morpholinoethyl substituents at various positions.


Gene cloning and structure--function relationship of cytokines such as TNF and interleukins.
The genes for a number of proteins, potentially useful in cancer therapy and collectively called "biological response modifiers", have been cloned and expressed in micro-organisms in recent years. These recombinant proteins, which are now available in pure form in nearly unlimited quantities, include interferons, interleukins and cytotoxins such as Tumor Necrosis Factor (TNF) and lymphotoxin. Most often the human gene has been cloned and expressed, with view to possible applications in medicine, but usually the mouse equivalent gene was also characterized in order to carry out syngeneic animal model experiments. TNF is selectively toxic for many transformed cell lines, either alone or in combination with interferon or inhibitors of RNA or protein synthesis. Cells sensitive to the cytotoxic action of TNF and cells unaffected by it nonetheless usually carry about an equal number of TNF receptors; hence it is the secondary, intracellular signal which makes the difference between a transformed cell and a normal, diploid cell. TNF can induce a number of different genes in a variety of cells; for example, endothelial cells express a surface antigen responsible for adherence of leucocytes. Another gene which is induced by TNF is interleukin 6 (also called 26 kDa protein or BSF-2). This interleukin, IL-6, is a growth and differentiation factor for B cells as well as for T cells; it is responsible for functions previously ascribed to hepatocyte-stimulating factor, but has no interferon activity. The toxic action of TNF on tumor cells must involve the release of arachidonic acid as phospholipase inhibitors block the TNF-induced effects.(ABSTRACT TRUNCATED AT 250 WORDS)


The relationship between visual discomfort and cortical excitability in cone-opponent stimuli.
Increased colour contrast can induce visual discomfort, but there is little research on the effect of hue. Colour is processed via one or more information streams or channels. We hypothesized that hues which activate more than one channel would induce greater visual discomfort, as they will demand greater neural resources. Normally-sighted young observers made discomfort judgments of isoluminant stimuli of varying hue and contrast whilst EEG was recorded. As predicted, stimuli recruiting more than one channel were more uncomfortable, and this increased with contrast. Uncomfortable stimuli showed increased N2 event-related potentials and decreased alpha-band oscillations, potentially indicating increased neural excitability. This is evidence that increased neural responses are related to visual discomfort for chromatic stimuli. Furthermore, it suggests that the origins of visual discomfort are in early visual areas, when colour is represented in a cone-opponent space, rather than later areas where colour representation is determined by perceptual similarity.


Serotonergic regulation of type II corticosteroid receptor binding in hippocampal cell cultures: evidence for the importance of serotonin-induced changes in cAMP levels.
The development of the hypothalamic-pituitary-adrenal response to stress is profoundly altered by environmental events. One target for environmental regulation within the hypothalamic-pituitary-adrenal axis is the hippocampal type II corticosteroid (or glucocorticoid) receptor system, which mediates the negative-feedback effects of glucocorticoids on hypothalamic-pituitary-adrenal activity. Thus, adult rats handled early in life show increased hippocampal type II corticosteroid receptor density and increased sensitivity to the inhibitory effects of circulating glucocorticoids on post-stress hypothalamic-pituitary-adrenal activity. Both effects persist throughout life. The effects of handling on type II corticosteroid receptor development are, at least in part, mediated by changes in hippocampal 5-hydroxytryptamine turnover. Moreover, 5-hydroxytryptamine can regulate type II corticosteroid receptor density in cultured hippocampal cells, providing a paradigm for examining the neurochemical mechanisms by which environmental stimuli might regulate neural differentiation. In the present studies, we examined the intracellular mechanisms underlying the effects of 5-hydroxytryptamine on type II corticosteroid receptors ([3H]RU 28362 binding) in hippocampal cell cultures. cAMP, but not cGMP, levels in cultured hippocampal cells were significantly increased by the addition of 5-hydroxytryptamine to the medium. The cAMP response to 5-hydroxytryptamine was biphasic: an initial increase in cAMP levels occurred in response to nanomolar 5-hydroxytryptamine concentrations (EC50 = 7.2 nM), while a second increase was apparent at low micromolar concentrations. 5-Hydroxytryptamine also increased [3H]RU 28362 binding (EC50 = 4.5 nM) with a maximal effect at a concentration of 10 nM. There was no further increase in [3H]RU 28362 binding even with higher, micromolar concentrations of 5-hydroxytryptamine.(ABSTRACT TRUNCATED AT 250 WORDS)


Effectiveness of mini-transverse incision versus traditional reduced technique in the treatment of carpal tunnel syndrome. A prospective cohort study.
Carpal tunnel syndrome has attracted attention as an occupational disease due to the dramatic increase on its magnitude, and its prevalence in the general population, who's has been reported from a 0.6 to 3.4%. Currently, there are various techniques for its approach. However, there is great controversy when it comes to establishing which of the methods is the most beneficial. The objective of this study was to compare the efficacy of the mini-transverse incision against the traditional longitudinal technique in treatment of carpal tunnel syndrome. A series of cases is presented, prospectively included, of patients with a diagnosis of carpal tunnel syndrome, who are beneficiaries of a government hospital. We present a series of cases with a diagnosis of carpal tunnel syndrome, which were performed with two different techniques. Both techniques were evaluated by comparing the recovery and work reintegration times, as well as the decrease in pain and the absence of complications. A total of 8 patients operated with a minimal incision and 9 with a traditional reduced incision were studied. Significant differences were shown in the days taken to return to work, with a median of 17.5 (q25-q75 14-21) days for mini-transverse incision group and of 28 (q25-q75 21-28) days for the longitudinal traditional incision group (p = 0.002). Likewise, differences were obtained in the visual analogue pain scale during the first week of evaluation 4 vs 7 (p = 0.000), in contrast to complications where there were no differences at all. The results obtained corroborate a greater efficacy of the mini-transverse incision technique, in reducing disability times. This favors the health institution to reduce the costs of rehabilitation and for the patient to have a prompt work reintegration. It is suggested to strengthen the scientific evidence that supports the use of this technique by exploring other areas such as functional status or long-term benefits.


Body size, energetic and foraging mode of raptors in central Chile : An inference.
An inferential analysis of the foraging mode (opportunist or mediate by prey selection) of a taxonomic assemblage of raptors in central Chile was conducted. The analysis of energetic aspects such as daily requirements of predators and energy supplied by the preys, with estimations of prey relative abundances and their incidence in the diet of raptors, led us to conclude that contrarly to the opportunistic hunting mode suggested by others authors, these predators apparently present prey selection (on a biomass basis). This phenomenon is particularly evident in raptors of small body size.


Searching the Cambridge Structural Database for the 'best' representative of each unique polymorph.
A computer program has been written that removes suspicious crystal structures from the Cambridge Structural Database and clusters the remaining crystal structures as polymorphs or redeterminations. For every set of redeterminations, one crystal structure is selected to be the best representative of that polymorph. The results, 243,355 well determined crystal structures grouped by unique polymorph, are presented and analysed.


Wound healing after excision of subcutaneous tumors treated with near-infrared photoimmunotherapy.
Near-infrared photoimmunotherapy (NIR-PIT) is a novel cancer therapy that employs a combination of infrared light and tumor-targeted monoclonal antibody-photoabsorber conjugates to cause both direct tumor necrosis and immunogenic cell death. NIR-PIT may have potential in the perioperative setting before surgery, and therefore it is important to know the effect of NIR-PIT on wound healing. Fifty mice were implanted with subcutaneous xenografts of N87 human gastric cancer cells, and tumors were excised after reaching a predetermined size. After excision, 30 mice were split into three groups: Controls, NIR-PIT 1 day prior to surgery and NIR-PIT 3 days prior to surgery. The quantity of reactive oxygen species (ROS) in each wound was measured on Postoperative Days 2 and 4, and mice were monitored weekly for 4 weeks for evidence of local tumor recurrence as well as clinical evidence of wound healing complications (eg, dehiscence, infection). The remaining 20 mice (10 controls, 10 treated with NIR-PIT 1 day prior to surgery) were sacrificed on either Postoperative Day 7 or 14, the skin around wounds were excised, and tensile strength was measured with a digital force gauge. There were no significant differences between treatment and control groups with respect to wound ROS levels, wound tensile strength, local tumor recurrence, or postoperative complication rates (P > .05). In conclusion, neoadjuvant (pre-operative) NIR-PIT shows no evidence of adverse wound healing effects, and it is likely a safe adjunctive treatment to surgery. Postoperative use of NIR-PIT merits investigation.


Crossover between classical and quantum shot noise in chaotic cavities.
The discreteness of charge in units of e led Schottky in 1918 to predict that the electrical current in a vacuum tube fluctuates even if all spurious noise sources are eliminated carefully. This phenomenon is now widely known as shot noise. In recent years, shot noise in mesoscopic conductors, where charge motion is quantum-coherent over distances comparable to the system size, has been studied extensively. In those experiments, charge does not propagate as an isolated entity through free space, as for vacuum tubes, but is part of a degenerate and quantum-coherent Fermi sea of charges. It has been predicted that shot noise in mesoscopic conductors can disappear altogether when the system is tuned to a regime where electron motion becomes classically chaotic. Here we experimentally verify this prediction by using chaotic cavities where the time that electrons dwell inside can be tuned. Shot noise is present for large dwell times, where the electron motion through the cavity is 'smeared' by quantum scattering, and it disappears for short dwell times, when the motion becomes classically deterministic.


Basal cell adenocarcinoma of the major salivary glands: A population-level study of 509 cases.
We sought to better characterize patient, tumor, and long-term survival characteristics of basal cell adenocarcinoma (BCAC) of the major salivary glands with the National Cancer Database (NCDB). Retrospective database review of the NCDB (1998-2012). We retrospectively reviewed the NCDB for all cases of major salivary gland BCAC with histologic code 8147/3. Relevant demographic, tumor, and survival variables were extracted and analyzed. COX multivariate regression was performed to identify prognosticators. Out of 36,224 major salivary gland cancers in the NCDB, we found 509 cases of BCAC (1.4%), 88% of which were in the parotid glands, 11.2% in the submandibular glands, and 0.8% in the sublingual glands. Age at diagnosis ranged from 18 to 92 years (average 64). No gender preference was found (50.7% male). Most tumors were 2 to 4 cm in size (47.3%). Regional (11.9%) and distant metastasis (1.8%) were uncommon. Overall survival at 5 and 10 years was 79% and 62%, respectively. Although numerous variables were found to significantly impact survival on univariate regression analysis, only age ≥ 65 (hazard ratio [HR] 2.55; 95% confidence interval [CI], 1.56-4.19; P < 0.001) and high primary tumor (T)-stage (HR 1.85; 95% CI, 1.16-2.95; P = 0.010) remained significant prognosticators in our multivariate model. For high T-stage disease, surgery with radiation had significantly better survival than surgery alone. Basal cell adenocarcinoma is a rare salivary malignancy with a good prognosis. Regional and distant metastasis were uncommon. Radiation with surgery may help for higher T-stage disease. Old age and high T-stage were significant predictors of worse survival. 4. Laryngoscope, 126:1086-1090, 2016.


Differential regulation of gelatinase A and B and TIMP-1 and -2 by TNFalpha and HIV virions in astrocytes.
Changes in the fine balance between matrix metalloproteinases and their tissue inhibitors, which drives extracellular matrix turnover, may be critical to central nervous system inflammation in HIV infection as well as in neurotoxicity. Although they do not produce virus when infected by HIV, astrocytes may be directly affected by the virion, because some viral proteins are known to transduce signaling in brain cells and are also sensitive to the major proinflammatory cytokine TNFalpha. We therefore studied the effects of HIV and TNFalpha on MMP-2, MMP-9 and their inhibitors, TIMP-1 and TIMP-2, in astrocytes, by zymography and ELISA, respectively, or by RT-PCR for both of them. HIV slightly increased the production of pro-MMP-2 and pro-MMP-9 by astrocytes, in a dose-dependent manner. TNFalpha strongly induced pro-MMP-9. TIMP-1 and TIMP-2 levels were affected only slightly, if at all, by HIV and TNFalpha. Thus, astrocyte/HIV contact may lead to extracellular matrix activation, which may be strongly amplified by the inflammatory response. Our data strongly suggest that, besides their physiological production of MMP-2, astrocytes would be a major source of MMP-9 in the inflamed brain.


Equity in development and access to health services in the Wild Coast of South Africa: the community view through four linked cross-sectional studies between 1997 and 2007.
After election in 1994, the South African government implemented national and regional programmes, such as the Wild Coast Spatial Development Initiative (SDI), to provoke economic growth and to decrease inequities. CIET measured development in the Wild Coast region across four linked cross-sectional surveys (1997-2007). The 2007 survey was an opportunity to look at inequities since the original 1997 baseline, and how such inequities affect access to health care. The 2000, 2004 and 2007 follow-up surveys revisited the communities of the 1997 baseline. Household-level multivariate analysis looked at development indicators and access to health in the context of inequities such as household crowding, access to protected sources of water, house roof construction, main food item purchased, and perception of community empowerment. Individual multivariate models accounted for age, sex, education and income earning opportunities. Overall access to protected sources of water increased since the baseline (from 20% in 1997 to 50% in 2007), yet households made of mud and grass, and households who bought basics as their main food item were still less likely to have protected sources of water. The most vulnerable, such as those with less education and less water and food security, were also less likely to have worked for wages leaving them with little chance of improving their standard of living (less education OR 0.59, 95%CI 0.37-0.94; less water security OR 0.67, 95%CI 0.48-0.93; less food security OR 0.43, 95%CI 0.29-0.64). People with less income were more likely to visit government services (among men OR 0.28, 95%CI 0.13-0.59; among women OR 0.33, 95%CI 0.20-0.54), reporting decision factors of cost and distance; users of private clinics sought out better service and medication. Lower food security and poorer house construction was also associated with women visiting government rather than private health services. Women with some formal education were nearly eight times more likely than women with no education to access health services for prevention rather than curative reasons (OR 7.65, 95%CI 4.10-14.25). While there have been some improvements, the Wild Coast region still falls well below provincial and national standards in key areas such as access to clean water and employment despite years of government-led investment. Inequities remain prominent, particularly around access to health services.