Theory and numerical simulation for a cylindrical array by broadband constant beam pattern approach.
A broadband constant beam pattern (CBP) array is an acoustic array whose beam patterns are independent of operating frequencies. In this article, the theoretical far-field acoustic beam pattern analytic formulations have been mathematically derived for a cylindrical array on an infinite rigid cylinder, after applying the Fourier series expansion, the Fourier sine or cosine transform, and the stationary phase method to the Helmholtz equation with boundary conditions. When the ratio of the array radius over the operating frequency wavelength was large, the horizontal (xoy) plane beam patterns demonstrated broadband CBP performances under the far-field conditions. The vertical (xoz) plane acoustic beam patterns are determined by the array vertical aperture shading's Fourier spectrum coupled with the residuals from the asymptotic approximations of the Hankel function and its derivative. The theoretical results matched with the results by Kirchhoff's integral numerical simulation with various horizontal shading examples for directional acoustic beams by the broadband CBP approach.


Evidence for two distinct energy scales in the Raman spectra of YBa2(Cu1-xNix)3O6.95.
We report electronic Raman scattering from Ni-substituted YBa2Cu3O6.95 single crystals with T(c) ranging from 92.5 to 78 K. The fully symmetrical A(1g) channel and the B(1g) channel which is sensitive to the d(x(2)-y(2)) gap maximum have been explored. The energy of the B(1g) pair-breaking peak remains constant under Ni doping while the energy of the A(1g) peak scales with T(c) ( E(A(1g))/k(B)T(c) = 5). Our data show that the A(1g) peak tracks the magnetic resonance peak observed in inelastic neutron scattering yielding a key explanation to the long-standing problem of the origin of the A(1g) peak.


High-grade prostatic intraepithelial neoplasia.
High-grade prostatic intraepithelial neoplasia (HGPIN) has been established as a precursor to prostatic adenocarcinoma. HGPIN shares many morphological, genetic, and molecular signatures with prostate cancer. Its predictive value for the development of future adenocarcinoma during the prostate-specific antigen screening era has decreased, mostly owing to the increase in prostate biopsy cores. Nevertheless, a literature review supports that large-volume HGPIN and multiple cores of involvement at the initial biopsy should prompt a repeat biopsy of the prostate within 1 year. No treatment is recommended for HGPIN to slow its progression to cancer.


Pulmonary regurgitation following total correction of tetralogy of Fallot.
A method is described for quantifying pulmonary regurgitation. This method is based on a comparison of the right and left ventricular stroke volumes which are determined from biplane angiocardiograms. These techniques were applied to study 18 postoperative patients with tetralogy of Fallot. In patients with an outflow patch, regurgitant fraction was well correlated with regurgitant area. The RVEDV/LVEDV ratio was also correlated well with regurgitant fraction. Although majority of patients maintained normal RV ejection fraction, there were small number of patients with large regurgitant fraction and decreased RV ejection fraction.


Enantioselective oxidative gold catalysis enabled by a designed chiral P,N-bidentate ligand.
A newly developed P,N-bidentate ligand enables enantioselective intramolecular cyclopropanation by a reactive α-oxo gold carbene intermediate generated in situ. The ligand design is based on our previously proposed structure (with a well-organized triscoordinated gold center) of the carbene intermediate in the presence of a P,N-bidentate ligand. A C2-symmetric piperidine ring was incorporated in the ligand as the nitrogen-containing moiety. A range of racemic transformations of α-oxo gold carbene intermediates have been developed recently, and this new class of chiral ligands could enable their modification for asymmetric synthesis, as demonstrated in this study.


Effects of chronically increased ambient CO2 concentrations on aerobic capacity.
As part of a joint NASA-ESA-DARA study on the effects of chronically increased CO2 concentrations in ambient air, changes in parameters indicating aerobic capacity were investigated by cycle ergometry. Two potential sources for reductions of aerobic capacities were hypothesized: 1) the adaptations to CO2 such as reduction in H(+)-buffer capacities which may influence muscle metabolism; 2) the reduced physical activities which may lead to a detraining effect. Four subjects were exposed to 0.7% and 1.2% CO2 concentration in a confined compartment for 23 d each with 3 mo in between the two campaigns. A combined exercise test was applied before, during (on days 5, 11, and 22) and after CO2 exposure. Comparing steady-states at 30 W and 80 W power, elevated ventilation was found increased during CO2 exposure with significant differences between the two campaigns. Peak oxygen uptake decreased over the period of CO2 exposure, but was found not significantly different on day 5 compared to pre-exposure measurements. This decrease was not dependent on the CO2 concentration. The lactate concentration at low exercise intensities was found elevated during CO2 exposure. A shift in reverse direction was observed after the CO2 exposure. Since peak oxygen uptake did not differ on day 5 and the lactate concentration was found increased, it was concluded that the potential changes in muscle metabolism by adaptation to elevated CO2 concentrations did not influence the aerobic capacities. Therefore, it was concluded that the changes in aerobic capacities are the result of the reduced physical activities of the subjects while living in the confined compartment.


Using the Motion of the Head-Neck as a Joystick for Orientation Control.
Head-neck interfaces have the potential to command and control orientation tasks when the hand-wrist is not available for use as a joystick. We pose the question in this paper-How well can the head-neck be used to perform orientation tasks when compared to the hand-wrist? Anatomically, the motion of the head-neck is similar to that of the hand-wrist. We hypothesize that the head-neck motion can be as effective as the motion of the hand-wrist to control orientation tasks. A study was designed to characterize the ability of head-neck to command and control general orientation tasks. Fourteen healthy participants were asked to control the head orientation of an avatar on a computer screen using the motion of their head-neck and hand-wrist, measured by a robotic neck brace and a conventional joystick, respectively. Visual feedback was given to the participants with the display of the target and the actual head orientations of the avatar. The outcomes were defined for comparison between the head-neck and hand-wrist motions as follows: 1) mean absolute error; 2) time delay in tracking continuous orientation trajectories; and 3) settling time to reach target orientations. The results showed that the performance outcomes were significantly better with the hand-wrist than that of the head-neck when used as a joystick. However, all participants successfully completed the tasks with the head-neck. This demonstrates that the head-neck can be used as a joystick for controlling three dimensional object orientations, even though it may not be as dexterous as the hand-wrist. These results have fundamental implications in the design of devices and interfaces with the human head-neck.


A 12-wk egg intervention increases serum zeaxanthin and macular pigment optical density in women.
Two carotenoids found in egg yolk, lutein and zeaxanthin, accumulate in the macular retina where they may reduce photostress. Increases in serum lutein and zeaxanthin were observed in previous egg interventions, but no study measured macular carotenoids. The objective of this project was to determine whether increased consumption of eggs would increase retinal lutein and zeaxanthin, or macular pigment. Twenty-four females, between 24 and 59 y, were assigned to a pill treatment (PILL) or 1 of 2 egg treatments for 12 wk. Individuals in the PILL treatment consumed 1 sugar-filled capsule/d. Individuals in the egg treatments consumed 6 eggs/wk, containing either 331 microg (EGG 1) or 964 microg (EGG 2) of lutein and zeaxanthin/yolk. Serum cholesterol, serum carotenoids, and macular pigment OD (MPOD) were measured at baseline and after 4, 8, and 12 wk of intervention. Serum cholesterol concentrations did not change in either egg treatment group, but total cholesterol (P = 0.04) and triglycerides (P = 0.02) increased in the PILL group. Serum zeaxanthin, but not serum lutein, increased in both the EGG 1 (P = 0.04) and EGG 2 (P = 0.01) groups. Likewise, MPOD increased in both the EGG 1 (P = 0.001) and EGG 2 (P = 0.049) groups. Although the aggregate concentration of carotenoid in 1 egg yolk may be modest relative to other sources, such as spinach, their bioavailability to the retina appears to be high. Increasing egg consumption to 6 eggs/wk may be an effective method to increase MPOD.


Augmented chemosensitivity in black-eyed white Mitfmi-bw mice, lacking melanocytes.
Microphthalmia-associated transcription factor (Mitf) is responsible for differentiation of melanocytes, and a recessive Mitf mutant, black-eyed white (bw) mouse, is characterized by the lack of melanocytes in the skin and inner ear. To search for the hitherto unknown roles of melanocytes, we analysed the ventilatory responses of unanaesthetized bw mice by whole body plethysmography. During air breathing, bw mice showed lower breathing frequency and larger tidal volume, compared with age-matched wild-type mice, although there was no difference in the minute ventilation. Importantly, bw mice present normal haematocrit values and red blood cell counts. We next measured the immediate ventilatory responses to acute hypoxia (10% O2) and to hyperoxic hypercapnia (10% CO2). Hypoxic and hypercapnic ventilatory responses represent the functions of the chemoreceptors in the carotid body and the brainstem, respectively. The bw mice retain the peripheral hypoxic and central hypercapnic sensing functions, but exhibited augmented ventilatory responses to both hypoxia and hypercapnia. Unexpectedly, RT-PCR analysis has shown the expression of melanocyte-specific Mitf mRNA in the brain of bw mice, suggesting the presence of leptomeningeal melanocytes. These findings suggest a functional link between skin melanocytes and the central respiratory controller that generates respiratory rhythm and pattern.


FlexStem: improving predictions of RNA secondary structures with pseudoknots by reducing the search space.
RNA secondary structures with pseudoknots are often predicted by minimizing free energy, which is proved to be NP-hard. Due to kinetic reasons the real RNA secondary structure often has local instead of global minimum free energy. This implies that we may improve the performance of RNA secondary structure prediction by taking kinetics into account and minimize free energy in a local area. we propose a novel algorithm named FlexStem to predict RNA secondary structures with pseudoknots. Still based on MFE criterion, FlexStem adopts comprehensive energy models that allow complex pseudoknots. Unlike classical thermodynamic methods, our approach aims to simulate the RNA folding process by successive addition of maximal stems, reducing the search space while maintaining or even improving the prediction accuracy. This reduced space is constructed by our maximal stem strategy and stem-adding rule induced from elaborate statistical experiments on real RNA secondary structures. The strategy and the rule also reflect the folding characteristic of RNA from a new angle and help compensate for the deficiency of merely relying on MFE in RNA structure prediction. We validate FlexStem by applying it to tRNAs, 5SrRNAs and a large number of pseudoknotted structures and compare it with the well-known algorithms such as RNAfold, PKNOTS, PknotsRG, HotKnots and ILM according to their overall sensitivities and specificities, as well as positive and negative controls on pseudoknots. The results show that FlexStem significantly increases the prediction accuracy through its local search strategy. Software is available at http://pfind.ict.ac.cn/FlexStem/. Supplementary data are available at Bioinformatics online.


Improved preferential tumor hyperthermia with regional heating and systemic blood cooling: a balanced heat transfer method.
Absorption of power in large body volumes can occur with some approaches used for hyperthermia treatment of cancer. A systemic heat absorption rate exceeding the heat dissipation rate can lead to systemic temperature elevation that limits the magnitude and duration of application of power and hence the degree of preferential tumor temperature rise. We describe a hyperthermia approach consisting of regional electromagnetic power absorption and extracorporeal blood cooling with regulation of both systemic heat absorption and dissipation rates ("balanced heat transfer"). A test of this approach in five dogs with nonperfused tumor models demonstrated intratumoral temperatures greater than 42 degrees C, while systemic temperature remained at 33 degrees C and visceral temperatures within the heated region equilibrated between 33 and 42 degrees C. Solutions of the bioheat transfer equation were obtained for a simplified model with a tumor perfusion rate lower than surrounding normal tissue perfusion rate. In this model, the use of arterial blood temperatures less than 37 degrees C allowed higher power densities to be used, for given normal tissue temperatures, than when arterial temperature was greater than or equal to 37 degrees C. As a result, higher intratumoral temperatures were predicted. Control of arterial blood temperature using extracorporeal cooling may thus (1) limit systemic temperature rise produced by regional heating devices and (2) offer a means of improving intratumoral temperature elevations.


A microfluidic SPLITT device for fractionating low-molecular weight samples.
In this article, we report the design of a microfluidic split flow thin cell (SPLITT) fractionation device with internal electrodes placed across the width of its analysis channel for assaying low-molecular weight samples. The reported device allows the realization of lateral electric fields and separation distances of the orders of 100 V/cm and 500 μm, respectively, that are suitable for fractionating such mixtures with high resolution. Our experiments show that a key challenge to realizing electrophoretic fractionations using the current design is to minimize the electroosmotically driven fluid circulations in its SPLITT channel that tend to hydrodynamically mix the liquid streams flowing through this duct. The present work addresses this challenge by chemically modifying the surface of our fluidic conduits with a new coating medium, N-(2-triethoxysilylpropyl) formamide, which has been shown to diminish electroosmotic flow in glass microchannels by over 5 orders of magnitude. Finally, we describe the integration of the reported microfluidic fractionation device to a mass spectrometer via the electrospray ionization interface to allow inline label-free detection of analytes in our assay. Product purity greater than 95% has been accomplished using the SPLITT system presented here for a sample of peptides having the same electrical polarity.


Linkage of loci associated with two pigment mutations on mouse chromosome 13.
Progeny from one intra- and two inter-specific backcrosses between divergent strains of mice were typed to map multiple markers in relation to two pigment mutations on mouse chromosome 13, beige (bg) and pearl (pe). Both recessive mutants on a C57BL/6J background were crossed separately with laboratory strain PAC (M. domesticus) and the partially inbred M. musculus stock PWK. The intra- and inter-specific F1 hybrids were backcrossed to the C57BL/6J parental strain and DNA was prepared from progeny. Restriction fragment length polymorphisms were used to follow the segregation of alleles in the backcross offspring at loci identified with molecular probes. The linkage analysis defines the association between the bg and pe loci and the loci for the T-cell receptor gamma-chain gene (Tcrg), the spermatocyte specific histone gene (Hist1), the prolactin gene (Prl), the Friend murine leukaemia virus integration site 1 (Fim-1), the murine Hanukuh Factor gene (Muhf/Ctla-3) and the dihydrofolate reductase gene (Dhfr). This data confirms results of prior chromosomal mapping studies utilizing bg as an anchor locus, and provides previously unreported information defining the localization of the prolactin gene on mouse chromosome 13. The relationship of multiple loci in relation to pe is similarly defined. These results may help facilitate localization of the genes responsible for two human syndromes homologous with bg and pe, Chediak-Higashi syndrome and Hermansky-Pudlak syndrome.


The In Vitro-In Vivo Safety Confirmation of PEG-40 Hydrogenated Castor Oil as a Surfactant for Oral Nanoemulsion Formulation.
Evaluation on the safety use of high concentration of polyoxyl 40 (PEG-40) hydrogenated castor oil as a surfactant for oral nanoemulsion was performed in Webster mice. As previously reported, nearly 20% of PEG-40 hydrogenated castor oil was used to emulsify the glyceryl monooleate (GMO) as an oil to the aqueous phase. Thermodynamically stable and spontaneous nanoemulsion was formed by the presence of co-surfactant polyethylene glycol 400 (PEG-400). Standard parameters were analyzed for nanoemulsion including particle size and particle size distribution, the surface charge of nanoemulsion, and morphology. To ensure the safety of this nanoemulsion, several cell lines were used for cytotoxicity study. In addition, 5000 mg/kg body weight (BW) of the blank nanoemulsion was given orally to Webster mice once a day for 14 days. Several parameters such as gross anatomy, body weight, and main organs histopathology were observed. In particular, by considering the in vivo data, it is suggested that nanoemulsion composed with a high amount of PEG-40 hydrogenated castor oil is acceptable for oral delivery of active compounds.


Reversible Ratiometric NADH Sensing Using Semiconducting Polymer Dots.
Reduced nicotinamide adenine dinucleotide (NADH) is a key coenzyme in living cells due to its role as an electron carrier in redox reactions, and its concentration is an important indicator of cell metabolic state. Abnormal NADH levels are associated with age-related metabolic diseases and neurodegenerative disorders, creating a demand for a simple, rapid analytical method for point-of-care NADH sensing. Here we develop a series of NADH-sensitive semiconducting polymer dots (Pdots) as nanoprobes for NADH measurement, and test their performance in vitro and in vivo. NADH sensing is based on electron transfer from semiconducting polymer chains in the Pdot to NADH upon UV excitation, quenching Pdot fluorescence emission. In polyfluorene-based Pdots, this mechanism resulted in an on-off NADH sensor; in DPA-CNPPV Pdots, UV excitation resulted in NADH-sensitive emission at two wavelengths, enabling ratiometric detection. Ratiometric NADH detection using DPA-CNPPV Pdots exhibits high sensitivity (3.1 μM limit of detection), excellent selectivity versus other analytes, reversibility, and a fast response (less than 5 s). We demonstrate applications of the ratiometric NADH-sensing Pdots including smartphone-based NADH imaging for point-of-care use.


Spectral studies on 33258 Hoechst and related bisbenzimidazole dyes useful for fluorescent detection of deoxyribonucleic acid synthesis.
Absorption, fluroescence and circular dichroism measrements on 33258 Hoechst-deoxyribonucleic acid (DNA) complexes are consistent with the existence of two types of dye-binding interactions. One type, which persists at elevated solution ionic strength, is highly specific for adenine-thymine-rich DNA. Dye bound under this condition exhibits efficient fluorescence and strong optical activity. A less specific, largely electrostatic interaction is associated with less intense fluorescence and weaker optical activity. The fluorescence of 33258 Hoechst and several other bisbenzimidazole dyes is less when bound to poly(deoxyadenylate-5-bromodeoxyuridylate) than when bound to poly(deoxyadenlyate-deoxythymidylate). Quenching of 33258 Hoechst fluorescence can also be used to detect biosynthetic incorporation of 5-bromodeoxyuridine into the DNA of living cells. This property of 33258 Hoechst should allow fluorescence-activated cell and chromosome sorting according to the extent of DNA synthesis, providing a bridge between biochemical and cytologic analyses of processes related to DNA replication.


Room-Temperature Polariton Lasing in All-Inorganic Perovskite Nanoplatelets.
Polariton lasing is the coherent emission arising from a macroscopic polariton condensate first proposed in 1996. Over the past two decades, polariton lasing has been demonstrated in a few inorganic and organic semiconductors in both low and room temperatures. Polariton lasing in inorganic materials significantly relies on sophisticated epitaxial growth of crystalline gain medium layers sandwiched by two distributed Bragg reflectors in which combating the built-in strain and mismatched thermal properties is nontrivial. On the other hand, organic active media usually suffer from large threshold density and weak nonlinearity due to the Frenkel exciton nature. Further development of polariton lasing toward technologically significant applications demand more accessible materials, ease of device fabrication, and broadly tunable emission at room temperature. Herein, we report the experimental realization of room-temperature polariton lasing based on an epitaxy-free all-inorganic cesium lead chloride perovskite nanoplatelet microcavity. Polariton lasing is unambiguously evidenced by a superlinear power dependence, macroscopic ground-state occupation, blueshift of the ground-state emission, narrowing of the line width and the buildup of long-range spatial coherence. Our work suggests considerable promise of lead halide perovskites toward large-area, low-cost, high-performance room-temperature polariton devices and coherent light sources extending from the ultraviolet to near-infrared range.


Total parenteral nutrition-associated changes in mouse intestinal intraepithelial lymphocytes.
Intraepithelial lymphocytes (IEL) play a major role in mucosal defense mechanisms against intraluminal foreign antigens. To address the role luminal nutrients have on the phenotype and function of the IEL, we administered total parenteral nutrition (TPN) to mice, with the absence of enteral intake. We hypothesized that administration of TPN would result in changes in the phenotype and function of the IEL. For this, we utilized a mouse model of TPN. A significant decline in the CD4+ IEL population occurred with TPN. Additionally, the CD8+,CD44+ IEL subset showed a 65% decline (P < 0.05), and the CD4+,CD44+ subset declined by 55% with TPN (P < 0.05). The CD8alphabeta+ population (a marker of thymic-dependence) also declined by 92% (P < 0.01) with TPN. IEL in the TPN group showed a significantly lower degree of in vitro proliferation. In conclusion, the IEL showed significant phenotypic changes with TPN including the loss of the thymic-derived population. Functionally, the IEL showed a significant decline in proliferation. Such changes demonstrate the important role luminal nutrients have on IEL phenotype and function.


[Age changes in the structure of adenohypophysical gonadotropocytes and hypothalamic arcuate nucleus neurocytes].
The results of cytochemical and electron-microscopic examinations show a similarity for age- and season-dependent changes in hormone secretion of the adenohypophysial gonadotropocytes and the arcuate nucleus function of the hypothalamus in geeze. Transition to sexual maturity and the reproductive period are connected with the intensive evacuation of secretory granules from the above-mentioned structures. The period of sexual quietness is characterized by the absence of secretory granules in the neurocytes of the arcuate nucleus and by a slow evacuation of secretion from gonadotropocytes.


Influence of Electrolyte Concentration on Single-Molecule Sensing of Perfluorocarboxylic Acids.
Perfluorocarboxylic acids (PFCAs) are an emerging class of persistent organic pollutants. During the fabrication process, it is unavoidable to form PFCA homologs or isomers which exhibit distinct occurrence, bioaccumulation, and toxicity. The precision measurement of PFCAs is therefore of significant importance. However, the existing characterization techniques, such as LC-MS/MS, cannot fully meet the requirement of isomer-specific analysis, largely due to the lack of authentic standards. Single-molecule sensors (SMSs) based on nanopore electrochemistry may be a feasible solution for PFCAs determination, thanks to their ultra-high spatiotemporal resolutions. Hence, as a first step, this work was to elucidate the influence of electrolyte concentration on the four most critical indicators of nanopore measurements, and furthermore, performance of nanopore SMSs. More specifically, three of the most representative short-chain PFCAs, perfluoropentanoic acid (PFPeA), perfluorohexanoic acid (PFHxA) and perfluoroheptanoic acid (PFHpA), were adopted as the target analytes, aerolysin nanopore was employed as the sensing interface, and 2, 3 and 4 M KCl solutions were used as electrolytes. It was found that, when the concentration of KCl solution increased from 2 to 4 M, the conductance of aerolysin nanopore increased almost linearly at a rate of 0.5 nS per molar KCl within the whole voltage range, the current blockade of PFPeA at -50 mV increased from 61.74 to 66.57% owing to the enhanced steric exclusion effect, the maximum dwell time was more than doubled from 14.5 to 31.5 ms, and the barrier limited capture rate increased by 8.3 times from 0.46 to 3.85 Hz. As a result, when using 4 M KCl as the electrolyte, over 90% of the PFPeA, PFHxA and PFHpA were accurately identified from a mixed sample, and the calculated limit of detection of PFPeA reached 320 nM, more than 24 times lower than in 2 M KCl. It was thus clear that tuning the electrolyte concentration was a simple but very effective approach to improve the performance of nanopore SMSs for PFCAs determination.


Pituitary cytology of the teleost fish Tilapia mossambica (Peters).
In the pituitary of Tilapia mossambica, eight cell types were identified on the basis of their staining reactions. the RPD consists of erythrosinophils and PbH positive cells. PbH cells border the NH and give amphipilic reaction to tri- and tetrachrome dyes and Halmi's stain. Erythrosinophils are also stained with acid fuchsin and orange G. The PPD is made up of acidophils and cyanophils. The acidophils are stained with orange G, acid fuchsin and erythrosin. These cells form a palisade zone between the neurohypophysis and the cyanophils. The cyanophils are AB, AF, ATh, PAS and aniline blue positive. They include both thyrotrophs and gonadotrophs and cannot be differentiated. The gonadotrophs may be those which are degranulated and vacuolated in the breeding season. The PI is formed of PAS- and PbH positive cells which lack any definite pattern of arrangement. Apart from the chromophils, scattered chromophobes were seen throughout the adenohypophysis. Occasionally, cells resembling the cyanophils of PPD were noticed in the RPD and PI also.


Comparison of serological and molecular tests to investigate Leishmania spp. infections in stray dogs from an area of intense visceral leishmaniasis transmission in Brazil.
The aim of this study was to investigate the level of exposure to Leishmania infection in stray dogs in an area of intense visceral leishmaniasis transmission in the state of Pernambuco, Brazil. Blood samples from 178 dogs were analyzed using serological and molecular assays: rapid immunochromatographic test (ICT), enzyme-linked immunosorbent assay (ELISA), immunofluorescence antibody test (IFAT), and conventional and quantitative polymerase chain reaction (cPCR and qPCR). Positivity values obtained with serological tests were 71.4% (127/178), 70.2% (125/178), and 50.6% (90/178) using ICT, ELISA, and IFAT, respectively, with 38.8% (69/178) of the dogs were simultaneously positive for all three tests. The positivity values obtained with cPCR and qPCR were 20.2% (36/178) and 38.8% (69/178), respectively, with 11.8% (21/178) testing positive in both molecular assays. Overall, 87.1% (155/178) were positive for anti-Leishmania spp. antibodies and/or Leishmania spp. DNA. Positivity to one or more tests was statistically associated with lymphadenomegaly, skin lesions, lymphocytosis, anemia and hyperproteinemia. The results of this study revealed a high level of exposure to Leishmania in stray dogs in an area of intense human visceral leishmaniasis transmission, suggesting that dogs play a role as reservoirs in the transmission cycle of this zoonosis.


A Vectorial Current Density Imaging Method Based on Magnetic Gradient Tensor.
Magnetic current imaging is deemed an emerging powerful technique for visualizing electrical currents in electronic devices. However, the existing magnetic-field-based Fourier Transform back-evolution method is limited by its mono-function of imaging the magnitude of current density in devices under test, and subject to background noise distortion. Here, we developed a novel vectorial current density imaging method based on the detection of the magnetic field gradient generated by current carrying conductors. A closed form solution of current density inversion was analytically derived and numerically verified. Experiments were conducted by scanning tri-axial fluxgate sensor over different shapes of electrical wires. The results show that a current density resolution of 24.15 mA/mm2, probe-to-sample separation of 2 mm, and spatial resolution of 0.69 mm were achieved over a maximum scanning area of 300 mm × 300 mm. Such a method is verified to be capable of simultaneously imaging both magnitude and directions of current density, which is a promising technique for in situ noninvasive inspection for the power electronic and semiconductor industry.


Preclinical approaches to assess potential kinase inhibitor-induced cardiac toxicity: Past, present and future.
Over a decade ago, use of tyrosine kinase inhibitors (TKIs) for the treatment of malignancies was found to cause left ventricular dysfunction, a finding that was unexpected and not well predicted by standard preclinical studies. Subsequently, several preclinical approaches were proposed to address this issue. Over the last 5 years, several approaches for preclinical evaluation of cardiac function using isolated perfused hearts, engineered heart tissue and human-induced pluripotent stem cell-derived cardiac myocytes have been shown to be relatively predictive of the cardiotoxic potential of TKIs. Further, preclinical studies submitted for regulatory review for recently approved KIs have demonstrated various forms of KI-induced cardiotoxicity. Thus, early identification and assessment of cardiotoxicity in the preclinical setting is now possible. Given that kinases are involved in diverse cellular processes common to both normal and tumor cells, KI-induced toxicity, particularly in the heart, appears difficult to avoid. To develop drugs with fewer adverse effects, better efficacy and safety assessments, such as pharmacological separation of targets for cancer from heart, and/or wider separation of the drug concentrations for antitumor activity from cardiac toxicity, may be helpful. Additional preclinical approaches for assessing drug efficacy and toxicity in parallel may include use of animal cancer models and a 3D integrated in vitro model of perfused tumor and heart tissues. Minimizing and predicting potential KI-induced cardiotoxicity is still an important regulatory challenge, and better preclinical approaches may help achieve this goal.


Deficient release of prostacyclin-like activity by rat stomach under stress.
It is known that a confinement procedure will promote histological alterations in the gastric mucosa of rats. It is our hypothesis that, under these conditions, there should be an alteration in prostacyclin metabolism. Our findings corroborate this idea, which makes us suppose that the deficient release of prostacyclin-like activity by the rat's stomach may play an important role in gastric mucosa vitality and in its consequent damage.


Single-stage reconstruction for soft tissue defects: a case series.
Various techniques for obtaining expedient aesthetic coverage of soft tissue defects with limited donor site morbidity have been developed, including the use of a dermal regeneration template (DRT) as the first step in a two-stage surgical approach. Use of DRT in reconstruction has increased as a result of reports suggesting improved cosmetic results and reduced scarring compared to split-thickness skin grafts (STSG), but this approach requires a return to the operating room. To evaluate outcomes of a single-stage procedure, a prospective evaluation of patients with complicated soft tissue defects measuring <200 cm2 was conducted. Following trauma or resection of a tumor, 20 patients underwent single-stage reconstruction with surgical debridement and application of a single-layered DRT and a meshed STSG. Negative pressure wound therapy (NPWT) was applied as a bolster with continuous -125 mm Hg pressure for 5 days. After 5 days, traditional dressings were applied and patients were followed until healed with a minimum follow-up of 5 months to a maximum follow-up of 19 months. Participants included 20 patients (14 men, six women; average age 60 years old [range: 27-92 years]; average wound size 104.5 cm2 [range: 40.0-180.0 cm2]). Wounds were located on the lower extremities (10 patients), upper extremities (seven patients), and trunk (three patients). Average graft take was 98.3% with an average take time of 5.6 days (SD 0.50). No significant differences in graft take rates between male and female patients, smokers and nonsmokers, and patients with and without diabetes mellitus were observed. Wound location also did not affect graft take rates. No wound breakdown, adverse events, or re-operation occurred during follow-up. In this case series, single-stage reconstruction using DRT, STSG, and NPWT was used with good outcomes and second-stage reconstruction surgery was avoided. Prospective, randomized, controlled clinical studies to compare the various surgical and wound care approaches to closing these tissue defects are warranted.


Megakaryocytes and inherited thrombocytopenias.
Inherited thrombocytopenias may be divided into two groups. In the first group, there is no marked thrombocytopathy. Although numerous in the bone marrow, megakaryocytes often are abnormal cytologically. A dysmegakaryocytopoiesis with defective platelet production is suggested but remains to be evidenced. In the second group, thrombocytopenias are accompanied with variable thrombocytopathy. The functional and biochemical platelet abnormalities responsible for these different thrombocytopathies often are well elucidated. The study of the relations with the occurrence of thrombocytopenia constitutes an interesting field of investigation.


Life-Course Reproductive History and Cardiovascular Risk Profile in Late Mid-Life: The CARDIA Study.
Background Reproductive events, that is, a preterm birth (PTB), small-for-gestational-age infant (SGA), and vasomotor symptoms of menopause, are associated with subclinical atherosclerotic cardiovascular disease (ASCVD). We evaluated whether women with a past PTB and/or SGA (henceforth PTB/SGA) were more likely to have severe vasomotor symptoms of menopause and whether the estimated 10-year ASCVD risk was higher in women with PTB/SGA and vasomotor exposures. Methods and Results We assigned 1866 women (mean age=55±1 years) in the CARDIA (Coronary Artery Risk Development in Young Adults) study to the following categories of reproductive exposures: none, PTB/SGA only, vasomotor symptoms only, or both PTB/SGA and vasomotor symptoms. We used Kruskal-Wallis tests to evaluate the differences in pooled cohort equation ASCVD risk scores by category and linear regression to evaluate the associations of categories with ASCVD risk scores adjusted for study center, body mass index, education, current hormone replacement therapy use, parity, and hysterectomy. Women with PTB/SGA were more likely to have severe vasomotor symptoms, 36% versus 30%, P<0.02. ASCVD risk score was higher in women with both PTB/SGA and vasomotor symptoms (4.6%; 95% CI, 4.1%-5.1%) versus women with no exposures (3.3%; 95% CI, 2.9%-3.7%) or vasomotor symptoms only (3.8%; 95% CI, 3.5%-4.0%). ASCVD risk score was higher in women PTB/SGA (4.8%; 95% CI, 3.6%-5.9%) versus no exposures. PTB/SGA and vasomotor symptoms was associated with ASCVD risk score in white women versus no exposures (β=0.40; 95% CI, 0.02-0.78). Conclusions Women with prior PTB/SGA were more likely to have severe vasomotor symptoms of menopause. Reproductive exposures were associated with an estimated 10-year ASCVD risk in white women.


Glucocorticoids enhance stability of human growth hormone mRNA.
We have studied the control of expression of the human growth hormone (hGH) gene introduced into the chromosomes of mouse fibroblasts. Cell lines transformed with the hGH gene expressed low levels of intact hGH mRNA and secreted hGH protein into the medium. Although the level of expression of hGH mRNA was low, the gene remained responsive to induction by glucocorticoid hormones. To localize the sequences responsible for induction and to determine the mechanism by which these cis-acting sequences enhance gene expression, we have constructed a series of fusion genes between the hGH gene and the herpes simplex virus (HSV) thymidine kinase (tk) gene. We have demonstrated that a fusion gene in which hGH cDNA is flanked at its 5' terminus by an HSV tk promoter and is flanked at its 3' terminus by 3' HSV tk DNA remains inducible by glucocorticoids. Our studies indicate that the hGH exons contain sequences which are responsible for glucocorticoid hormone induction. Pulse-chase experiments, in vitro nuclear transcription, and approach to steady-state measurements indicate that the mechanisms responsible for induction of the hGH cDNA fusion gene operate posttranscriptionally to enhance the stability of hGH mRNA. Moreover, this increased stability was associated with an increase in the length of the 3' poly(A) tail on hGH mRNA.


[Changes in the calcitonin content after inhalation injury in dogs].
To investigate the changes in the serum content of immunoreactive calcitonin (iCT) after burns or inhalation injury, and to explore its diagnostic significance. Twenty-four dogs were randomized into 4 groups, i. e. A (n = 6, with moderate degree inhalation injury) , B ( n = 6, with severe inhalation injury), C (n = 6, with most severe inhalation injury) and D (n = 6, with severe burns) groups. The serum content of iCT and blood gas analysis before and after injury were determined at different time points. The degree of inhalation injury was determined with fibrobronchoscopic examination at 6 post-inhalation injury hour (PIH). (1) Fiber bronchoscopic examination showed that the degree of inhalation injury in each group was coincident with the anticipation. (2) The serum content of iCT in each group at 1 PIH was obviously higher than that before injury, and it was evidently higher in A, B and C groups than that in D group at 4 PIH. The peak value of iCT in group A at 24 PIH was (453+/-224) ng/L, and it increased gradually in B and C groups at 48 PIH. The serum content of iCT increased continually from 2 PIH on, and it reached (125+/-41) ng/L at 48 PIH. (3) Compared with PaO2 value before injury (109+/-8) mmHg, there was no obvious difference of the PaO, in A and D groups. PaO2 value in B and C group began to descend continually at 8 PIH (65+/-6) mmHg, and that in C group began to descend at 4 PIH (71+/-9) mmHg. PaCO2 value in C group began to increase at 24 PIH(52+/-11) mmHg when compared with that before injury(38+/-5 ) mmHg. The changes in the serum level of iCT within 8 PIH occurred much earlier than PaO2 and PaCO2, thus it has the same diagnostic significance as fibers bronchoscopic examination.


Prokaryotic ammonium transporters: what has three decades of research revealed?
The exchange of ammonium across cellular membranes is a fundamental process in all domains of life. In plants, bacteria and fungi, ammonium represents a vital source of nitrogen, which is scavenged from the external environment. In contrast, in animal cells ammonium is a cytotoxic metabolic waste product and must be excreted to prevent cell death. Transport of ammonium is facilitated by the ubiquitous Amt/Mep/Rh transporter superfamily. In addition to their function as transporters, Amt/Mep/Rh proteins play roles in a diverse array of biological processes and human physiopathology. Despite this clear physiological importance and medical relevance, the molecular mechanism of Amt/Mep/Rh proteins has remained elusive. Crystal structures of bacterial Amt/Rh proteins suggest electroneutral transport, whilst functional evidence supports an electrogenic mechanism. Here, focusing on bacterial members of the family, we summarize the structure of Amt/Rh proteins and what three decades of research tells us concerning the general mechanisms of ammonium translocation, in particular the possibility that the transport mechanism might differ in various members of the Amt/Mep/Rh superfamily.


Extracorporeal circuit pressure profiles during continuous venovenous haemofiltration.
Continuous renal replacement therapy machines are capable of providing continuous pressure measurements at different points of the extracorporeal circuit. This study investigates the pattern of circuit pressure changes during high-volume continuous venovenous haemofiltration (CVVH) with regional anticoagulation with anticoagulant citrate dextrose in formula A. Extracorporeal circuit pressures during 91 treatments of CVVH were analysed. Distinct patterns of extracorporeal circuit pressures were observed: (a) the extracorporeal circuit pressures during a routine uncomplicated CVVH treatment remained close to initial values. The interquartile range (IQR) of pressures during the treatments were as follows: PA (arterial pressure) -3.5 to -10 mmHg, PV (venous pressure) 51 to 41.5 mmHg, PBE (prefilter pressure) 120.5 to 104 mmHg, PD2 (fluid outlet pressure) -23 to -70 mmHg, TMP (transmembrane pressure) 142.75 to 102.75 mmHg and PFD (pressure filter difference) 70 to 62 mmHg. (b) PD2 and TMP showed early separation from baseline values in CVVH treatment compromised by haemofilter clot. Haemofilter clotting problems were associated with median PD2 of -164 mmHg (IQR: -66.2 to -228.7), a fourfold increase from baseline. (c) PA and PV values changed abruptly in catheter-malfunction-related circuit disruption. Poorly functioning catheters tended to have a higher baseline PA (median: -33 versus -25.5) than in those without catheter problems; however, the difference was not statistically significant (p= 0.13). (d) A rise in PBE and PFD followed by changes in PD2 and TMP were noted in a treatment disrupted because of air detection chamber clotting. Distinct patterns of extracorporeal circuit pressures were present in patent and disrupted CVVH circuits. We suggest that the pattern of pressure profiles, not absolute values, may be more relevant in clinical practice.


Altruistic surrogacy and informed consent.
A crucial premise in many recent arguments against the moral permissibility of surrogate motherhood arrangements is the claim that a woman cannot autonomously consent to gestating and relinquishing a child to another couple, because she cannot be fully informed about what her future emotional responses will be to the foetus developing within her, and to the giving up of the newborn infant to its social parents. When conjoined with some moral principle about the justifiable limits on the ways others can be expected to exercise their autonomy on our behalf, this claim is often taken to establish that various forms of surrogate motherhood arrangements are morally wrong. In this paper I want to show that there is a serious non sequitur in this kind of argument. That is, I want to show that even if women cannot in fact have this kind of information about what their future emotional responses to pregnancy and relinquishment will be, nothing follows about the wrongness or otherwise of surrogacy. For, when we consider what counts as informed consent in the context of other important ventures with uncertain consequences, it becomes clear that informed consent does not require having this kind of information about one's future emotional states. In putting these arguments, I also hope to clarify some of the connections which might be thought to hold between informed consent and autonomous decision-making generally.


A clinical review of communication training for haematologists and haemato-oncologists: a case of art versus science.
The art of communication at times seems at odds with the science of medicine. Poor communication is associated with risks for patient and physician. Communication skills are highly relevant for haematologists and are associated with increased physician and patient satisfaction, positive psychosocial outcomes and possible health outcomes. Medical communication training has recently become widespread but is largely restricted to junior medical professionals. In haematology, the proliferation of high quality communication skills is low and there are few interventions catering for the required skillset. A review identified five applicable interventions for haematologists. There is variation in intervention length and structure, and most studies measure targeted skill fidelity rather than patient outcomes. Work on motivation and empowerment holds potential for haematological conditions, but is largely absent from care. This review highlights the need for new interventions for haematologists which focus on producing and maintaining positive patient outcomes.


Online ejaculation training programs promote non-evidence-based treatment of male sexual dysfunction.
Purposefully reducing the frequency of ejaculation, coined "semen retention", and the similar practice of "NoFap", have been popularized on social media. They are frequently accompanied by unsubstantiated claims of health benefits. Their increasing popularity has led to the emergence of online courses claiming to teach these techniques. The goal was to characterize the landscape of courses offering ejaculatory training. A systematic Google search was performed using terms related to ejaculation training to identify training programs. Information regarding instructor credentialing, type and duration of courses, costs, and claims of medical benefits were extracted. Eleven ejaculation training courses were identified with 10 instructors (two courses named the same coach). Costs varied from $5 to $147 per week or a $20 to $199 one-time payment. None of the course instructors claimed standardized credentials in the fields of medicine or mental health. Seven instructors (70%) solely cited their own personal experience as their qualifying credentials. Courses claimed to improve erectile dysfunction, premature ejaculation, porn addiction, sexual performance anxiety, testosterone levels, and/or depression. Ejaculation training programs are costly, readily available online, and provided by instructors with no medical background. Despite no scientific evidence, these courses claim to improve various aspects of men's health and can be potentially damaging financially, physically, and mentally to participants.


immunodeficiency in ataxia-telangiectasia.
Ataxia-telangiectasia is characterized by endocrine, neurologic, hematologic, hepatic, cutaneous and immunologic abnormalities. The immunologic deficiencies vary considerably from patient to patient, and in each patient with respect to time. The most frequent deficiencies of humoral immunity are diminished or absent serum and salivary IgA, diminished or absent serum IgE and impaired antibody responses to a variety of bacterial and viral antigens. Deficiencies of cellular immunity are commonly found by both in vivo and in vitro analyses. Histologic confirmation of these immunodeficiencies is readily observed in the lymphoid tissue. The thymus, which may be the seat of the primary abnormality in the immunodeficiency syndrome, regularly shows morphologic characteristics of an embryonic thymus.


Isolation and antiproliferative activity of triterpenoids and fatty acids from the leaves and stem of Turraea vogelii Hook. f. ex benth.
Chloroform extract from the leaves of Turraea vogelii Hook f. ex Benth demonstrated cytotoxic activity against a chronic myelogenous leukemia cell, K-562 with IC50 of 14.27 μg/mL, while chloroform, ethyl acetate and methanol extracts from the stem of the plant inhibited K-562 cells growth with IC50 of 19.50, 24.10 and 85.40 μg/mL respectively. Bioactive chloroform extract of Turraea vogelii leaves affords two triterpenoids: oleana-12,15,20-trien-3β-ol (1), and oleana-11,13-dien-3β,16α,28-triol (2), with six fatty esters, ethyl hexaeicos-5-enoate (3), 3-hydroxy-1,2,3-propanetriyltris(tetadecanoate) (4), 1,2,3-propanetriyl(7Z,7'Z,7''Z)tris(-7-hexadecenoate) (5), 1,2,3-propanetriyl(5Z,5'Z,5''Z)tris(-5-hexadecenoate) (6), 1,2,3-propanetriyltris(octadecanoate) (7), and 2β-hydroxymethyl tetraeicosanoate (8). Tetradecane (9), four fatty acids: hexadecanoic acid (10), tetradecanoic acid (11), (Z)-9-eicosenoic acid (12), and ethyl tetradec-7-enoate (13) were isolated from chloroform extract of Turraea vogelii stem. 1,2,3-propanetriyltris(heptadecanoate) (14), (Z)-9-octadecenoic acid (15) and (Z)-7-tetradecenoic acid (16) were isolated from ethyl acetate extract while (Z)-5-pentadecenoic acid (17) was obtained from methanol extract of the plant stem. Compounds 1, 2, 5, 6, 11, 12, 15, 16 and 17 exhibited pronounced antiproliferative activity against K-562 cell lines.


A Dynamic Tandem Repeat in Monocotyledons Inferred from a Comparative Analysis of Chloroplast Genomes in Melanthiaceae.
Chloroplast genomes (cpDNA) are highly valuable resources for evolutionary studies of angiosperms, since they are highly conserved, are small in size, and play critical roles in plants. Slipped-strand mispairing (SSM) was assumed to be a mechanism for generating repeat units in cpDNA. However, research on the employment of different small repeated sequences through SSM events, which may induce the accumulation of distinct types of repeats within the same region in cpDNA, has not been documented. Here, we sequenced two chloroplast genomes from the endemic species Heloniopsis tubiflora (Korea) and Xerophyllum tenax (USA) to cover the gap between molecular data and explore "hot spots" for genomic events in Melanthiaceae. Comparative analysis of 23 complete cpDNA sequences revealed that there were different stages of deletion in the rps16 region across the Melanthiaceae. Based on the partial or complete loss of rps16 gene in cpDNA, we have firstly reported potential molecular markers for recognizing two sections (Veratrum and Fuscoveratrum) of Veratrum. Melathiaceae exhibits a significant change in the junction between large single copy and inverted repeat regions, ranging from trnH_GUG to a part of rps3. Our results show an accumulation of tandem repeats in the rpl23-ycf2 regions of cpDNAs. Small conserved sequences exist and flank tandem repeats in further observation of this region across most of the examined taxa of Liliales. Therefore, we propose three scenarios in which different small repeated sequences were used during SSM events to generate newly distinct types of repeats. Occasionally, prior to the SSM process, point mutation event and double strand break repair occurred and induced the formation of initial repeat units which are indispensable in the SSM process. SSM may have likely occurred more frequently for short repeats than for long repeat sequences in tribe Parideae (Melanthiaceae, Liliales). Collectively, these findings add new evidence of dynamic results from SSM in chloroplast genomes which can be useful for further evolutionary studies in angiosperms. Additionally, genomics events in cpDNA are potential resources for mining molecular markers in Liliales.


Adverse cerebral events detected after subarachnoid hemorrhage using brain oxygen and microdialysis probes.
A prospective observational study was conducted to investigate whether episodes of ischemia are detected by continuous cerebral monitoring and whether such episodes are related to clinical outcome. Forty patients (35 after subarachnoid hemorrhage and 5 after complex aneurysm surgery) were monitored for a total of 174 days (mean, 4 d; range, 1-12 d). Brain tissue partial pressures of oxygen and carbon dioxide, pH, and temperature were measured continuously using Neurotrend sensors (Codman, Bracknell, England). Bedside analysis of extracellular chemistry was performed hourly using microdialysis. Glasgow Outcome Scale score was assessed at 3 to 6 months. Patients with poor World Federation of Neurosurgical Societies grades (4 and 5) or an unfavorable outcome (severe disability or death) had, on average, higher lactate and lactate/pyruvate ratio but lower glucose/lactate ratio (P < or = 0.05). Brain tissue partial pressure of oxygen decreased to below 1.1 kPa in 78% of the patients for 18% (95% confidence interval, 12-24%) of time monitored. There were 197 episodes in which brain tissue partial pressures of oxygen decreased to below 1.1 kPa for at least 30 minutes. Unfavorable outcome was associated with more of these episodes (8.8 episodes; 95% confidence interval, 4.4-13.2 episodes) than favorable outcome (2.2 episodes; 95% confidence interval, 1.1-3.3 episodes), as well as an episode of glutamate levels of more than 10 micromol/L or lactate/pyruvate ratio more than 40 (P < 0.05, chi(2) test). Intraparenchymal oximetry and microdialysis can detect but fail to predict the development of delayed cerebral ischemia. There were associations between episodes of low brain oxygen, abnormal microdialysis, and unfavorable outcome, but these associations were weak.


Older widows' experience of home care.
Scholars and practitioners have defined home care as a set of services that older persons receive at home. There have been few empirical studies of the essence of the experience. To describe the experience of home care for older widows living alone in their own homes. Findings are reported from one aim of the study, which was to discern the phenomena that were descriptive of the experience of the sample as a whole. A descriptive phenomenological method was used. Participants met inclusion criteria for duration of widowhood, continuing residence in their own homes since the husband's death, number of adult children, self-rated health, and study-specific mental competence. Over a 3-year period, seven tape-recorded interviews were conducted in the homes of 25 widows over the age of 80. Foci of interest were the women's perceptions, actions, and intentions relative to their helpers and the help they had while living alone. The structures of the experience and its context were discerned and detailed in the form of taxonomies of phenomena and contextual features. The common phenomena were sorting out who can best do what needs to be done, protecting my standby, mobilizing my standby to help with this job too, and working together to get the job done. A new definition of home care was proposed, incorporating those phenomena. These older widows were not merely receiving home-care services. They were negotiating reliance on their standby helpers in specific ways. As home-care nurses plan care with widows and their other helpers, they should set aside standard definitions of home care that pertain to providing services and focus on the intentions of the older widows whom they serve.


Characteristics of the Allele Pool and the Genetic Differentiation of Goats of Different Breeds and their Wild Relatives by Str-Markers.
Based on 16 STR-loci, the allele pool and interbreed differentiation of goat breeds of Russian and foreign breeding were investigated in this study. These breeds included Karachai (KRCH-K, n=73, mountain zone; KRCH-Z, n=33, foothill zone), Dagestan Downy (DAGD, n=30), Dagestan Wool (DAGW, n=30), Soviet Wool (SOVW, n=30), Saanen (SAAN, n=34), Murciano-Granadina (MURS, n=37), as well as wild goats, represented by three species of mountain goats (n=52): Siberian Capricorn (Capra sibirica) of Altai (CSIB-S, n=6), Tajikistan (CSIB-T, n=4), Kyrgyzstan (CSIB-K, n=6), and the Himalayas (CSIB-H, n=4); Bezoar goat (Capa aegagrus) of Turkey (CAEG, n=3) and Pakistan (CAEG-S, n=3); West Caucasian tur (Capra caucasica): western Caucasian (Kuban, CCAU-K, n=10), central Caucasian (CCAU-M, n=8), and eastern Caucasian (Dagestan, CCAU-D, n=8). The highest genetic diversity was observed in the North Caucasus breeds, such as Karachai, Dagestan Downy, and Dagestan Wool. The mean numbers of alleles per locus and allelic diversity were 7.385-9.154 and 7.353-7.713, respectively. The genetic proximity of Caucasian breeds was confirmed by cluster analysis, and they formed a common branch with the highest genetic affinity, while the Orenburg and Soviet Wool breeds formed another branch, and the third branch with the least affinity was the dairy breed of foreign selection.The analysis of the phylogenetic tree of domestic and wild species established the formation of three clusters formed by the subspecies of the West Caucasian tur, Siberian ibex, and breeds of domestic goats. At the same time, populations of the Bezoar goats were localized at the root of the last cluster, which confirmed their role as the ancestors of domestic goats.


Information science for the future: an innovative nursing informatics curriculum.
Health care is increasingly driven by information, and consequently, patient care will demand effective management of information. The report of the Priority Expert Panel E: Nursing Informatics and Enhancing Clinical Care Through Nursing Informatics challenges faculty to produce baccalaureate graduates who use information technologies to improve the patient care process and change health care. The challenge is to construct an evolving nursing informatics curriculum to provide nursing professionals with the foundation for affecting health care delivery. This article discusses the design, implementation, and evaluation of an innovative nursing informatics curriculum incorporated into a baccalaureate nursing program. The basic components of the curriculum framework are information, technology, and clinical care process. The presented integrated curriculum is effective in familiarizing students with informatics and encouraging them to think critically about using informatics in practice. The two groups of students who completed the four-course sequence will be discussed.


Maternal smoking in pregnancy and reproductive hormones in adult sons.
Smoking during pregnancy has been reported to alter levels of reproductive hormones in adult sons. From a Danish pregnancy cohort established in 1984-1987, 347 out of 5109 sons were selected according to their exposure to tobacco smoke in foetal life. From February 2005 to January 2006, a blood sample from each young man (18-21 years) was collected and analysed for reproductive hormones. There were no apparent trends of increasing or decreasing hormonal levels with increased exposure to maternal tobacco smoking during pregnancy. Only the free testosterone/free estradiol ratios increased with increased maternal smoking during pregnancy (p for trend = 0.05). No trends for increasing odds ratios for high follicle-stimulating hormone (> or =25 percentile) or low inhibin B (< or =25 percentile) in relation to maternal smoking were observed. We found no major indication of long-term effects of pre-natal exposure to tobacco smoke on the levels of reproductive hormones later in life, but the data may suggest a shift in the hypothalamo-pituitary-gonadal axis towards higher androgenicity. This result was, however, of only borderline significance and could be because of chance.


Alloreactive delayed-type hypersensitivity in graft recipients: complexity of responses and divergence from acute rejection.
Immunocompetent allograft recipients typically exhibit evidence of sensitization to graft antigens through alloantibody production and allograft rejection, as well as delayed-type hypersensitivity (DTH) reactivity to donor antigens. Most previous studies have relied on whole donor splenocytes, which primarily elicit allorestricted allogeneic responses, to test specific DTH responses and overlook the independent element of self-restricted responses in host-allograft interactions. We tested expression of self-MHC-restricted versus allo-MHC-restricted allogeneic DTH responses in both nonimmunosuppressed and tolerized C57BL/6 mice. Mice were sensitized for allogeneic DTH either by rejection of skin or cardiac allografts, or by subcutaneous injection of intact allogeneic splenocytes. Patterns of alloreactive DTH were compared in allosensitized, tolerant, and naive hosts. All three methods of allosensitization resulted in equivalent self-restricted and allorestricted allogeneic DTH responses in nonimmunosuppressed mice. Gallium nitrate blocked acute rejection of cardiac allografts, and also blocked allosensitization of both self-restricted and allorestricted DTH responses, but did not influence the expression of DTH responses in presensitized mice. Gallium nitrate treatment could not block acute rejection of skin allografts, but interfered with sensitization for self-restricted, but not allorestricted, DTH responses in these recipients. This divergence of self- versus allo-MHC-restricted allosensitization for DTH was observed in two additional situations: the rates of allosensitization for self-restricted versus allorestricted DTH, and the acquisition of allorestricted, but not self-restricted, alloreactive DTH responses in cardiac allograft tolerant mice subsequently challenged with a skin allograft. These studies demonstrate that acute rejection correlates generally with allogeneic DTH, whereas tolerance is associated with a lack of alloreactive DTH. However, self-restricted and allorestricted allosensitization can operate independently in allograft recipients. Thus, the relationships between alloreactive DTH and graft-induced allosensitization, acute rejection, or tolerance are more complicated than previously appreciated.


Quantifying Thermal Disorder in Metal-Organic Frameworks: Lattice Dynamics and Molecular Dynamics Simulations of Hybrid Formate Perovskites.
Hybrid organic-inorganic materials are mechanically soft, leading to large thermoelastic effects which can affect properties such as electronic structure and ferroelectric ordering. Here we use a combination of ab initio lattice dynamics and molecular dynamics to study the finite temperature behavior of the hydrazinium and guanidinium formate perovskites, [NH2NH3][Zn(CHO2)3] and [C(NH2)3][Zn(CHO2)3]. Thermal displacement parameters and ellipsoids computed from the phonons and from molecular dynamics trajectories are found to be in good agreement. The hydrazinium compound is ferroelectric at low temperatures, with a calculated spontaneous polarization of 2.6 μC cm-2, but the thermal movement of the cation leads to variations in the instantaneous polarization and eventually breakdown of the ferroelectric order. Contrary to this the guanidinium cation is found to be stationary at all temperatures; however, the movement of the cage atoms leads to variations in the electronic structure and a renormalization in the bandgap from 6.29 eV at 0 K to an average of 5.96 eV at 300 K. We conclude that accounting for temperature is necessary for quantitative modeling of the physical properties of metal-organic frameworks.


[Experimental study on diabetes and pregnancy: with special reference to the effects of insulin treatment on fetuses of diabetic dams].
Through the development of treatment of diabetes mellitus, diabetic cases of pregnancy have been increasing, and the effects of maternal hyperglycemia and insulin-treated hypoglycemia on the growth and life of fetuses and newborns are becoming very important problems. However, it is difficult for us to investigate the fetuses of human diabetic mothers as experimental models. Although many reports deal with the development of newborns of diabetic mothers and about their secretory changes of insulin and C-peptide reactivity, there have been few reports concerning the effects of severe diabetes on pregnancy and the effects of insulin treatment on fetuses. Concerning experimental animals, there are also few reports about the effects of insulin treatment on diabetic pregnant animals. We conducted the present investigation to determine the effects of insulin treatment on the growth and metabolism of the fetuses of diabetic pregnant rats. Virgin female Wistar rats weighing 200 approximately 300 g were caged overnight with male rats. The mated females were isolated and the gestational age was calculated from noon of this day (zero). Seventeen of 24 pregnant rats received a rapid intravenous injection of 50 mg/kg body weight of streptozotocin (STZ) in 0.4 ml of 0.01 M citrate buffer (pH 4.5) immediately after blood samples were collected through the jugular vein under light ether anaesthesia on the 5th day of gestation. Seven pregnant rats were injected with only 0.4 ml of citrate buffer and served as the controls. These rats were divided into four groups, and each group was named as follows: Normal pregnant rats group (group I, n = 7), diabetic pregnant rats group (group II, n = 6) and insulin-treated diabetic pregnant rats group (group III: plasma glucose level 60 approximately 300 mg/dl, n = 6 and group IV: plasma glucose level below 60 mg/dl, n = 5). Group III and IV rats were treated with a subcutaneous injection of Lente Insulin (from 2 u. to 6 u.) every day from the 13th to the 19th day of gestation. Group II rats were injected with saline every day in the same way. Maternal blood samples were collected under light ether anaesthesia after feeding ad libitum on the 5th and 12th days of gestation. On the 20th day of gestation, the pregnant rats were anaesthetized by an intraperitoneal injection of sodium pentobarbital, and blood samples were collected in the manner stated above. Each fetus and placenta was taken out individually by hysterotomy.(ABSTRACT TRUNCATED AT 400 WORDS)


Doping control analysis of selected peptide hormones using LC-MS(/MS).
With the constantly increasing sensitivity and robustness of liquid chromatography-mass spectrometry-based instruments combined with enhanced reproducibility as well as mass accuracy and resolution, LC-MS(/MS) has become an integral part of sports drug testing programs particularly concerning the detection of peptide hormones. Although several of the relevant peptidic drugs such as insulins (Humalog LisPro, Novolog Aspart, etc.), growth hormone releasing peptides (GHRPs, e.g., GHRP-2, GHRP-6, Hexarelin, etc.), and insulin-like growth factors (e.g., IGF-1, IGF-2, long-R(3)-IGF-1) are currently analyzed using dedicated top-down analytical procedures, i.e. employing specifically tailored sample preparation procedures followed by targeted LC-MS(/MS) measurements focusing on intact analytes, first approaches towards multi-analyte methods have been established. These allow the determination of the prohibited substances in blood and urine doping control specimens following therapeutic applications. In addition, the use of new complementary devices such as ion mobility analyzers, e.g., in hybrid mass spectrometers yielded promising data for the differentiation of isobaric insulins, which outlines the potential to further accelerate and multiplex doping control analytical assays to meet the continuously increasing demands of rapid and unambiguous test methods. Moreover, the potential of LC-MS/MS to target recombinant peptide hormones such as human growth hormone using bottom-up approaches has been demonstrated by targeting proteotypic peptides that unambiguously differentiate the recombinant molecule from the naturally occurring and endogenously produced analog.


Early identification of patients with an acute coronary syndrome as assessed by dispatchers and the ambulance crew.
This study was performed to evaluate the possibility of early identification of patients with an acute coronary syndrome who are transported by ambulance. All patients in the community of Göteborg who were transported by ambulance over a period of 3 months owing to symptoms raising any suspicion of an acute coronary syndrome were studied. In all 930 cases that were included in the survey, 130 (14%) had a final diagnosis of acute myocardial infarction (AMI) and 276 (30%) had a final diagnosis of an acute coronary syndrome. Independent risk indicators for development of AMI were: male sex (odds ratio 1.70; 95% confidence limits 1.02-2.84), cold and clammy on admission of the ambulance crew (odds ratio 2.07; 95% confidence limits 1.23-3.49) and showing electrocardiogram (ECG) signs of myocardial ischemia on admission to the emergency department (odds ratio 8.78; 95%confidence limits 5.28-14.61). Independent predictors for development of an acute coronary syndrome were: male sex (odds ratio 1.97; 95% confidence limits 1.30-2.99), a history of angina pectoris (odds ratio 3.41; 95% confidence limits 2.24-5.26), cold and clammy on admission of the ambulance crew (odds ratio 1.95; 95% confidence limits 1.21-3.15), and ECG signs of myocardial ischemia on admission to the emergency department (odds ratio 5.55; 95% confidence limits 3.63-8.58). Among patients seen by the ambulance crew with symptoms raising any suspicion of an acute coronary syndrome, predictors for that diagnosis included male sex, a history of angina pectoris, patients being cold and clammy on admission of the ambulance crew, and ECG signs of myocardial ischemia on admission to the emergency department.


The differential contribution of capsaicin-sensitive afferents to behavioral and cardiovascular measures of brief and persistent nociception and to Fos expression in the formalin test.
Intraplantar injection of dilute formalin evokes brief (Phase 1) and persistent (Phase 2) increases in primary afferent activity, pain behavior, and cardiovascular responses, and induces spinal cord Fos-like immunoreactivity (Fos-LI). Although previous studies demonstrated that the destruction of small diameter primary afferents with neonatal capsaicin treatment decrease formalin-evoked nociception, these studies only evaluated behavioral responses, and did not distinguish between Phase 1 and 2. To address these questions, we simultaneously evaluated formalin-evoked pain behavior (flinching of the afflicted paw), cardiovascular responses (heart rate and mean arterial pressure), and lumbar spinal cord Fos expression in control rats and in rats treated with capsaicin (100 mg/kg) one day postpartum. We found that neonatal capsaicin-treated rats, compared to controls, exhibited similar cardiovascular responses and slightly less flinching behavior during Phase 1. During Phase 2, however, capsaicin-treated rats exhibited 59% less flinching and 45% smaller heart rate responses. Also, in capsaicin-treated rats, we counted 59% fewer Fos-labeled neurons in the spinal cord. These results indicate that capsaicin-sensitive afferents contribute to formalin-evoked behavioral and cardiovascular responses and to spinal cord neuronal responses. The differential effect of neonatal capsaicin on nociception during Phase 1 and Phase 2 suggests that sensitization mechanisms during Phase 1 do not contribute to the magnitude of nociceptive responses during Phase 2.


[Plant ABC transporters--the family with tradition].
ATP binding cassette (ABC) transporters, which are found in all species, are known mainly for their ability to confer drug resistance. They have been thoroughly studied in mammals, where they became the center of interest for clinical reasons related to the resistance of tumor cells to chemotherapy treatment. Less is known about plant members of the ABC family, however, growing number of reports on their role in different physiological processes attract attention. The vacuolar ABC transporters in plants characterized to date are involved in the intracellular sequestration of cytotoxins (e.g. herbicides), as well as the products of endogenous metabolism like chlorophyll catabolites. Others localized within plasma membrane are active in the transport of secondary metabolites or phytohormones. Finally certain transporters are present in cell organelles and play a role in such processes as P oxidation. Here, we briefly introduce these proteins, and describe structural characteristic and physiological aspect of their activity in a plant cell.


Startup performance of the traveling wave versus standing wave linear accelerator.
The startup performance of medical linear accelerators is of increasing importance for modern radiotherapy techniques. The traveling wave-type linear accelerator of the SL series of Philips (now Elekta Oncology Systems) has been modified in its flight tube design to meet this goal of a fast rise time of the radiation field. The new slitless flight tube combined with a redesigned gun servo electronic now achieves start up times of the radiation comparable with those of a standing wave linear accelerator (Siemens Mevatron) according to our measurements.


[Sequential endovenous angiourography (AUS) with image subtraction for the study of the arterial phase of urography. Comparison with nephroangiotomography (NAT)].
Two urographical techniques employed in the endovenous study of renal arteries are compared. They are nephroangiotomography (NAT) using synchroplan and sequential angiourography (SAV) with image subtraction. 64 patients were studied, 32 with NAT and 32 with AVS. Both techniques were shown to be useful, but AVS through infrequently used was cleary more efficient than Nat in the study of the vascular arterial phase.


Trajectories of objectively measured physical function among older breast cancer survivors in comparison with cancer-free controls.
Aging associated with progressive declines in physical function is well-known; however, it is unclear how breast cancer diagnosis affects the trajectories of physical function over a long period of time. The current study examined the trajectories in objective measures of physical function over 20 years for women with breast cancer and matched controls. 2712 community-dwelling women (452 breast cancer cases and 1:5 matched cancer-free controls) aged 65 years or older at baseline (1986-1988) within the Study of Osteoporotic Fractures were followed for 20 years. Objective physical function was assessed up to 9 times, including hand grip strength, timed chair stand, gait speed and quadriceps strength. Linear mixed models were used to model physical function changes in terms of secular time trend, group (cases or controls), period (pre-and post-diagnosis status), and their interaction terms. We observed all measures of physical function declined over time. While no differences in trends between cases and controls during the pre-diagnosis period were observed, after cancer diagnosis, grip strength and gait speed declined significantly faster in cases than controls. Quadriceps strength significantly decreased ~ 7 pounds shortly after breast cancer diagnosis, and then improved over time. Our study revealed that older breast cancer survivors relative to older women without cancer had significantly worse declines in grip strength and gait speed. Breast cancer survivors also had a sharp, short-term drop followed by gradual improvement over time in quadriceps strength. These findings suggest exercise training targeting muscle strength and mobility would be beneficial among older breast cancer survivors.


In Silico and in Vitro-Guided Identification of Inhibitors of Alkylquinolone-Dependent Quorum Sensing in Pseudomonas aeruginosa.
Pseudomonas aeruginosa is a major opportunistic pathogen in cystic fibrosis, wound and nosocomial infections, posing a serious burden to public health, due to its antibiotic resistance. The P. aeruginosa Pseudomonas Quinolone System (pqs) quorum sensing system, driven by the activation of the transcriptional regulator, PqsR (MvfR) by alkylquinolone (AQ) signal molecules, is a key player in the regulation of virulence and a potential target for the development of novel antibacterial agents. In this study, we performed in silico docking analysis, coupled with screening using a P. aeruginosa mCTX::PpqsA-lux chromosomal promoter fusion, to identify a series of new PqsR antagonists. The hit compounds inhibited pyocyanin and alkylquinolone signal molecule production in P. aeruginosa PAO1-L and PA14 strains. The inhibitor Ia, which showed the highest activity in PA14, reduced biofilm formation in PAO1-L and PA14, increasing their sensitivity to tobramycin. Furthermore, the hepatic and plasma stabilities for these compounds were determined in both rat and human in vitro microsomal assays, to gain a further understanding of their therapeutic potential. This work has uncovered a new class of P. aeruginosa PqsR antagonists with potential for hit to lead optimisation in the search for quorum sensing inhibitors for future anti-infective drug discovery programs.


Use of luminescent Leptospira interrogans for enumeration in biological assays.
Rapid and reliable in vitro methods for the detection of pathogenic leptospires, such as Leptospira interrogans, are lacking. The present study investigated the use of luminescence to replace the existing enumeration techniques. Transposon TnSC189 was modified to incorporate the luxCDABE cassette from Photorhabdus luminescens and was used to construct luminescent Leptospira spp. There was a linear relationship between luminescence and cell number, with the theoretical detection limit being less than 10(4) leptospires. A comparison of enumeration by a standard method (counting by dark-field microscopy) and enumeration by luminescence was conducted with luminescent L. interrogans. There was a good correlation between the two methods of enumeration (R(2) = 0.766), although variation in the luminescence early and late in growth phase reduced the degree of correlation. To demonstrate the utility of luminescence as a viability and cell number reporter, in vitro assays, including MIC determination, an extracellular matrix binding experiment, and a complement killing experiment, were conducted. In each case, the results obtained by luminescence matched those obtained by traditional means with high correlations (binding assay R(2) = 0.916, complement killing assay R(2) = 0.988). A strain expressing the luxCDABE transposon retained virulence in the hamster model of infection. Despite some variation in luminescence as a result of the growth phase or the particular assay conditions, enumeration by luminescence was found to be a quick, reliable, and highly sensitive method for the in vitro detection of leptospires that has the potential to replace more time-consuming methods of enumeration.


Apolipoprotein A-II augments monocyte responses to LPS by suppressing the inhibitory activity of LPS-binding protein.
Lipopolysaccharide (LPS) binding protein (LBP) plays an important role in regulating leukocyte responses to LPS. Remarkably, it may either augment these responses at low LBP concentrations or inhibit them at high concentrations. We previously reported that native high-density lipoprotein (HDL) augments human monocyte responses to LPS by suppressing the inhibitory activity of high concentrations of LBP, a process that occurs before HDL can inhibit the response by subsequently binding and neutralizing LPS. We now show that this novel activity is conferred largely by an HDL component protein, apolipoprotein (apo)A-II. Purified apoA-II was highly active in our assays. We also found that HDL from apoA-II-deficient mice was almost completely inactive, whereas the activities of HDLs that lacked apoA-I, apoC-I, apoE, or apoC-III were similar to that of wild-type HDL. Decreased activity was also observed in rabbit HDL, which is naturally deficient in apoA-II. Incorporating human apoA-II into rabbit HDL increased its activity to levels found in human HDL. Our investigation of the mechanism of apoA-II activity revealed that LBP promoted the formation of large LPS aggregates with low bioactivity and that apoA-II inhibited the formation of these aggregates without binding and directly inhibiting LPS bioactivity. Our results suggest a novel pro-inflammatory activity of apoA-II that may help maintain sensitive host responses to LPS by suppressing LBP-mediated inhibition. Our findings also raise the possibility that the decline of plasma apoA-II during sepsis may help control the response to LPS.


Off-label and unlicensed drug treatments in Neonatal Intensive Care Units: an Italian multicentre study.
The use of medicines among newborns admitted to intensive care units is characterized by a high prevalence of off-label/unlicensed use and a wide variability in the absence of international guidelines. A prospective cross-sectional study was organized with the aim to analyse drug prescriptions among all 107 Italian level III neonatal intensive care units. An online questionnaire was used to collect detailed information for each newborn, and a classification was made about the license status of all prescriptions. In addition, prescriptions were analysed taking into account a practical guide prepared by the Italian Society of Neonatology (ISN). The 1-day survey (May–July 2014) regarded 220 newborn infants admitted to 36/107 Italian neonatal intensive care units: 191 prematures and 29 born at term. In total, 720 prescriptions (corresponding to 79 different drugs) were analysed: 191 (26.5 %) followed the terms of the product license, 529 (73.5 %) were off-label or unlicensed: 193/220 newborns (87.7 %) received at least one off-label/unlicensed prescription. Antiinfectives were the most common medicine used, followed by respiratory drugs and antianaemics; in an off-label manner, the most common was cardiovascular and central nervous system (CNS) drugs, gastrointestinals and antiinfectives. The most common categories of off-label use were age (34.4 %) and dosing frequency (20.6 %). Compared to ISN practical guide, prescriptions adhered more frequently to indications (100 % for ampicillin/sulbactam, >80 % for ampicillin, fluconazole, fentanyl, ranitidine and vancomicin). Our results confirm the high prevalence of off-label/unlicensed drug use in the neonatal population and underline a better adherence to indications based on clinical practice, suggesting the need to update information contained in the data sheets of medicines.


Inferior Vena Cava Thrombus in a Postpartum Patient With Fontan Physiology: A Case Report.
Women with complex congenital heart disease, such as those with single-ventricle physiology, are surviving into adulthood and becoming pregnant. Because of their complex physiology, common peripartum complications pose unique risks. We describe a patient with a single ventricle who underwent an external vascular conduit, nonfenestrated Fontan procedure in childhood and then presented during the postpartum period with extensive thrombosis in her lower extremity deep venous system and inferior vena cava. In this article, we will discuss single-ventricle physiology and the implications of pregnancy, anesthetic considerations, and data for maternal and fetal outcomes in this population.


A Rare Case of Malignant Melanoma of the Mandible: CT and MRI Findings.
Malignant melanoma of the mandibular gingiva is extremely rare. It is a malignant tumour of melanocytes or their precursor cells, and often misinterpreted as a benign pigmented process. A few reports have described computed tomography (CT) and magnetic resonance imaging (MRI) findings of malignant melanoma in the oral cavity. We report a rare case of malignant melanoma of the mandible and the related CT and MRI findings. Soft tissue algorithm contrast-enhanced CT showed an expansile mass and irregular destruction of alveolar bone in the right side of the mandibular molar area. MR images showed an enhancing mass and the tumour had a low to intermediate signal intensity and a high-signal intensity. Soft tissue algorithm contrast-enhanced CT and MR images showed lymphadenopathy involving the submandibular lymph nodes. Histopathological examination confirmed the diagnosis of malignant melanoma.


Self-Administered Test Is Useful in Detecting Cognitive Changes.
According to this study: The Self-Administered Gerocognitive Examination detected significant changes at least six months earlier than the Mini-Mental State Examination in patients with mild cognitive impairment who later developed dementia and in those who had Alzheimer disease dementia.Use of the brief, self-administered test may remove some barriers to identifying cognitive changes.


Updated epidemiology of workers exposed to metalworking fluids provides sufficient evidence for carcinogenicity.
The 1998 National Institute for Occupational Safety and Health (NIOSH) criteria document for metalworking fluids (MWF) is the most recent authoritative review of mortality studies of workers with these exposures. NIOSH concluded that substantial evidence exists for increased risk of cancer at several sites (larynx, rectum, pancreas, skin, scrotum, and bladder) among workers exposed to MWF before the mid-1970s, and that evidence is equivocal for cancer at several other sites, including stomach, esophagus, lung, prostate, brain, colon, and hematopoietic system. The UAW believes that systematic analysis of that body of data makes a much stronger case for stomach cancer related to MWF exposure. Since the Criteria document, the mortality experience of three of the cohorts reviewed has been either updated or reanalyzed. These updates strengthen the evidence for increased mortality from stomach and liver cancer, and non-malignant respiratory disease associated with exposure to water-based metalworking fluids. Additional toxicological data providing clear evidence for carcinogenicity of diethanolamine, a widely used ingredient, also increases the biological plausibility of these findings. Despite changes in composition of MWFs with time, and reduced exposure levels, these data contradict the notion that cancer risks have been eliminated.


Synthesis of γ-hydroxypropyl P-chirogenic (±)-phosphorus oxide derivatives by regioselective ring-opening of oxaphospholane 2-oxide precursors.
The synthesis of P-chirogenic (±)-phosphine oxides and phosphinates via selective nucleophilic ring opening of the corresponding oxaphospholanes is described. Two representative substrates: the phosphonate 2-ethoxy-1,2-oxaphospholane 2-oxide and the phosphinate 2-phenyl-1,2-oxaphospholane 2-oxide were reacted with various Grignard reagents to produce a single alkyl/aryl product. These products may possess further functionalities in addition to the phosphorus center such as the γ-hydroxypropyl group which results from the ring opening and π-donor moieties such as aryl, allyl, propargyl and allene which originates from the Grignard reagent.


Haemophilus influenzae Type a Sequence Type 23, Northern Spain.
Two consecutive cases of Haemophilus influenzae type a sequence type 23 invasive infection in 2 children attending the same daycare in 2019 triggered epidemiologic surveillance of H. influenzae infections in northern Spain. Despite the invasiveness potential of this virus strain, we detected no additional cases for 2013-2020.


Visuomotor functions of central thalamus in monkey. I. Unit activity related to spontaneous eye movements.
The region in and around the thalamic internal medullary lamina (IML) in the cat recently has been shown to contain neurons active with ocular saccades and responding to visual stimuli. In the present study, single-unit microelectrode recordings were made in the corresponding thalamic region of the alert monkey in order to determine whether neurons with similar properties existed. Our objective was to specify the functional characteristics of these thalamic cells in the monkey, since 1) cell populations in the central thalamus form an important link between brain stem structures, such as superior colliculus and paramedian pontine reticular formation, and cortical areas, such as frontal eye field and inferior parietal lobule; and 2) most neurophysiological information on these structures with regard to gaze mechanisms has been obtained in primates. In this first part of the study we report observations on 164 thalamic units whose activity was related to the performance of spontaneous eye movements, head fixed. The animals had been trained on a visual discrimination task but photic stimuli were used only for calibrating the eye-position recording and for inducing small saccades and smooth pursuit. The experiments were performed in dim red light and in total darkness. Three types of units were found: 67 saccadic burst units, 58 saccade pause-rebound units, and 39 eye-position units. Sixty-two of the burst units had a directional preference. Most of the on-directions were contraversive, and it was in such units that the lead time of firing before saccades was the longest (up to at least 400 ms). Some of the burst units had a movement field, others fired more intensively and with a longer lead time, depending on the eccentricity of the eye position reached in orbit. The five units with no directional preference were the ones showing the best relation of burst duration with saccade duration. Three types of pause-rebound units were distinguished, depending on whether the saccadic pause or the postsaccadic burst was the most conspicuous event or the pause occurred after saccade offset. The three types were called, respectively, omnipausers, omnirebound cells, and late pausers. Omnipausers and omnirebound cells had no directional preference but their typical firing patterns occurred very consistently with all saccades, even less than 2 degrees. In a few units, the rebound progressively faded away in total darkness. The relation of firing rate of eye-position units with eccentricity of the eyes in orbit was analyzed. Fluctuations in time and a hysteresis effect were found to affect this relation.(ABSTRACT TRUNCATED AT 400 WORDS)


Antibiotic resistant tuberculosis in the United Kingdom: 1993-1999.
The re-emergence of tuberculosis as a global health problem over the past two decades, accompanied by an increase in tuberculosis drug resistance, prompted the development of a comprehensive national surveillance system for tuberculosis drug resistance in 1993. The UK Mycobacterial Resistance Network (Mycobnet), which includes all mycobacterial reference and regional laboratories in the UK, collects a minimum dataset on all individuals from whom an initial isolate of Mycobacterium tuberculosis complex has been isolated and submitted by source hospital laboratories. Data sought include susceptibility to first line antibiotics, demographic, geographical, and risk factor information. There were 25 217 reports of initial isolates of M tuberculosis complex in the UK between 1993 and 1999. All were tested for sensitivity to isoniazid, rifampicin, and ethambutol and 12 692 of the isolates were also tested for sensitivity to pyrazinamide and streptomycin. A total of 1523 (6.1%) isolates were resistant to one or more drugs, 1397 isolates (5.6%) were resistant to isoniazid with or without resistance to other drugs, and 299 (1.2%) were multidrug resistant. Although the numbers of drug resistant isolates increased over the period, the proportions remained little changed. Certain groups of people were at a higher risk of acquiring drug resistant tuberculosis including younger men, residents of London, foreign born subjects, patients with a previous history of tuberculosis and those infected with HIV. Although the proportion of drug resistant tuberculosis cases appears to be stable in the UK at present, more than one in 20 patients has drug resistant disease at diagnosis and more than one in 100 has multidrug resistant disease. Tuberculosis control measures should be strengthened to minimise the emergence of drug resistance through rapid diagnosis, rapid identification of drug resistance, supervised treatment, and maintenance of comprehensive surveillance.


Interaction of arsenic trioxide As2O3 with DNA and RNA.
Arsenic salts have been used for centuries to treat a variety of medical conditions ranging from infectious disease to cancer. More recently, trivalent arsenic trioxide was found to exhibit high antitumor activity towards hematological malignancies. Even though much is known about antitumor activity and DNA damage by As2O3, there has been no report on the interaction of arsenic trioxide with isolated DNA or RNA. Therefore, it was of interest to examine the interaction of As2O3 with DNA and RNA in aqueous solution at physiological pH. FTIR and UV-visible difference spectroscopic methods were used to characterize the nature of drug-DNA and drug-RNA interactions and to determine the As binding site, the binding constant, the sequence selectivity, the helix stability, and the biopolymer secondary structure in the As2O3-polynucleotide complexes in vitro. The FTIR spectroscopic studies were conducted with As2O3-polynucleotide (phosphate) ratios of 1/40, 1/20, 1/10, and 1/5, with a final DNA (P) or RNA (P) concentration of 6.25 mmol/l. Spectroscopic results showed As2O3 binds to DNA and RNA at G-C, A-T, and A-U bases, and no interaction with the backbone PO2 group. As2O3-DNA and -RNA adducts showed one type of binding with overall binding constant of K(As2O3-DNA) = 1.24 x 10(5) M(-1) and K(As2O3-RNA) = 2.60 x 10(5) M(-1). The As2O3-polynucleotide complexation is associated with a partial biopolymer aggregation and no major alterations of B-DNA or A-RNA structure.


Tumor Necrosis Factor Alpha -308G/A Gene Polymorphisms Combined with Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratio Predicts the Efficacy and Safety of Anti-TNF-α Therapy in Patients with Ankylosing Spondylitis, Rheumatoid Arthritis, and Psoriasis Arthritis.
Background: TNF-α has been reported to be closely associated with autoimmune inflammatory diseases. This study aims to investigate the role of TNF-α -308(rs1800629) G/A gene polymorphisms as well as neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in predicting the efficacy and safety of TNF inhibitors (TNFi) in patients with ankylosing spondylitis (AS), rheumatoid arthritis (RA), and psoriasis arthritis (PsA). Methods: A total of 515 subjects (181 AS, 144 RA, 48 PsA, 10 hyperbilirubinemia, 10 hyperlipidemia and 122 healthy control) were recruited in this study. The accuracy of RT-PCR methods for identifying individual TNF-α -308 genotypes was assessed using sequencing as the gold standard. Baseline NLR and PLR of patients with AS, RA and PsA and healthy controls (HC) were calculated and compared. Meanwhile, differences between responders and non-responders to TNFi treatment as well as between individuals with and without adverse effects (AE) among responders were compared. Results: The RT-PCR method is stable and reliable for TNF-α -308G/A gene polymorphism analysis, independent of sample status. The GG genotype was overwhelmingly represented, with relatively few GA genotype, whilst the AA genotype was not detected in this study. There was no observed association between TNF-α-308G/A polymorphism and susceptibility in AS, RA or PsA patients. Patients with AS, RA, and PsA had a higher NLR, compared to the HC group. Apart from PsA patients, AS and RA patients had a higher PLR, compared to the HC group. NLR was positively correlated with PLR. Furthermore, a lack of response was more frequently observed in AS and RA patients that carrying the GA genotype than the GG genotype. AS and RA patients with AE had higher NLR and PLR, compared with the non-AE group. Conclusion: Our study preliminarily shown that combining TNF-α -308G/A polymorphisms with NLR and PLR can predict the responsiveness and safety of anti-TNF therapy in patients with AS or RA.


[Initial management of acute heart failure in the emergency department].
Acute decompensated heart failure is one of the most leading diseases among elderly patients presenting in the emergency department with a chief complaint of dyspnea. Initial management is crucial for the patient's outcome. In this article we propose a review of diagnosis, treatment, stratification and orientation of patients admitted to emergency department with acute heart failure in light of recent recommendations.