Intravenous immunoglobulins for neonatal alloimmune neutropenia refractory to recombinant human granulocyte colony-stimulating factor.
Neonatal alloimmune neutropenia (NAN) results from neutrophil destruction by transplacental maternal neutrophil-specific immunoglobulin G (IgG) antibodies directed against the antigen inherited from the father. Treatment is usually based on recombinant human granulocyte colony-stimulating factor (G-CSF) and prevention or treatment of infection. We report the case of neutropenia in a newborn discovered because of fetomaternal infection. The bone marrow biopsy showed normal cellularity. Granulocyte typing, granulocyte cross-matching, and serum assays showed anti-neutrophil antibodies specific for human neutrophil antigen-1c, an antigen rarely involved in this disease. This NAN was refractory to G-CSF but responded to intravenous immunoglobulin (IVIG). IVIG should be considered as a second-line treatment in NAN refractory to G-CSF. Clinical trials, however, are required to define the optimal management of NAN, a rare but probably underestimated life-threatening situation for newborns.


Polymorphic analysis of a pharmaceutical preparation by NIR spectroscopy.
A method for the characterization and determination of the crystalline from present in the amorphous miokamycin of a pharmaceutical preparation using near-infrared spectroscopy (NIRS) is proposed. The study leading to the development of the proposed method involved both qualitative (classification by residual variance analysis) and quantitative aspects (the determination of both total miokamycin and its crystalline form using multivariate calibration). Samples containing less than 5% of the total amount of miokamycin in its crystalline form can be accurately classified. Partial least-squares regression (PLSR) allows low contents of the crystalline form to be determined with absolute errors less than 1.5%, which is comparable to the limit of detection of the X-ray diffraction technique used as reference. Also, the total miokamycin content is determined by NIRS with errors less than 1%. The simplicity, expeditiousness and robustness of the proposed method make it an effective tool for determining both total and crystalline miokamycin in solid dosage forms.


Active sensing system with in situ adjustable sensor morphology.
Despite the widespread use of sensors in engineering systems like robots and automation systems, the common paradigm is to have fixed sensor morphology tailored to fulfill a specific application. On the other hand, robotic systems are expected to operate in ever more uncertain environments. In order to cope with the challenge, it is worthy of note that biological systems show the importance of suitable sensor morphology and active sensing capability to handle different kinds of sensing tasks with particular requirements. This paper presents a robotics active sensing system which is able to adjust its sensor morphology in situ in order to sense different physical quantities with desirable sensing characteristics. The approach taken is to use thermoplastic adhesive material, i.e. Hot Melt Adhesive (HMA). It will be shown that the thermoplastic and thermoadhesive nature of HMA enables the system to repeatedly fabricate, attach and detach mechanical structures with a variety of shape and size to the robot end effector for sensing purposes. Via active sensing capability, the robotic system utilizes the structure to physically probe an unknown target object with suitable motion and transduce the arising physical stimuli into information usable by a camera as its only built-in sensor. The efficacy of the proposed system is verified based on two results. Firstly, it is confirmed that suitable sensor morphology and active sensing capability enables the system to sense different physical quantities, i.e. softness and temperature, with desirable sensing characteristics. Secondly, given tasks of discriminating two visually indistinguishable objects with respect to softness and temperature, it is confirmed that the proposed robotic system is able to autonomously accomplish them. The way the results motivate new research directions which focus on in situ adjustment of sensor morphology will also be discussed.


Esmolol and beta-adrenergic blockade.
Tachycardia often presents difficult management problems in anesthesia. Because it increases myocardial oxygen demand so sharply, tachycardia can quickly place patients at risk of myocardial ischemia. It can occur for any number of reasons. Deepening the anesthetic, either with inhalation agent or opioids, will ablate increases in heart rate, but changes in heart rate are often transient and changes in anesthetic depth are often not. Esmolol (Brevibloc) is a unique, short-acting beta blocker that is strongly beta 1 selective at usual clinical doses. As with other beta blockers, esmolol becomes less selective for the beta 1 receptor as its dose is increased. It is metabolized by red blood cell esterases resulting in a half-life of 9 minutes. Fifteen minutes after a bolus dose, esmolol is difficult to detect in the plasma. Its metabolites have clinically undetectable activity and are eliminated renally. Esmolol may be administered by intermittent, intravenous bolus doses or by continuous infusion. Infusions should be preceded by loading doses. Dose range varies with the patient's status, clinical situation, concomitant medications, and desired result. Patients receiving esmolol should be monitored because of its bradycardic and hypotensive effects.


c-Met Overexpression in Cervical Cancer, a Prognostic Factor and a Potential Molecular Therapeutic Target.
This study aimed to assess the association between pretreatment c-Met overexpression in local-regional advanced cervical cancer patients treated definitively with concurrent chemoradiation therapy (CRT) and treatment outcomes including overall survival (OS), progression-free survival (PFS), distant metastases (DM) control, and local-regional control (LC). This Institutional Review Board-approved study included cervical cancer patients treated definitively and consecutively with CRT. Evaluation of cytoplasmic immunoreactivity for c-Met was performed and scored semiquantitatively by 3 pathologists, blinded to the treatment outcomes, and incorporated both the intensity and percentage of immunoreactivity in invasive carcinoma (H score). Treatment outcomes were reviewed and reported. Outcomes were stratified by c-Met overexpression and tumor characteristics. OS, PFS, LC, and DC rates were obtained via the Kaplan-Meier method and differences between groups were evaluated by the log-rank test. Hazard ratios were obtained via Cox regression for both univariate and multivariate analyses. The 5-year OS, PFS, LC, and DC were 57.18%, 48.07%, 72.11%, and 62.85%, respectively. Ten (35.7%) and 18 patients (64.3%) had c-Met H index >30 and<30, respectively. c-Met overexpression was significantly associated with worse 3- and 5-year OS (P=0.003), PFS (P=0.002), LC (P=0.01), and DC (P=0.0003). Patients with c-Met overexpression had a hazard ratio of 6.297, 5.782, 6.28, and 18.173 for the risks of death, disease progression, local recurrence, and DM, respectively. c-Met overexpression could be a potential predictive marker and therapeutic target for local-regional advanced cervical cancer patients treated definitively with CRT.


Mechanisms of frost resistance in Arabidopsis thaliana.
Freezing resistance strategies vary in Arabidopsis depending on origin. Southern accessions may avoid or tolerate freezing, while northern ones are always tolerant and reduce the proportion of freezable tissue water during acclimation. Survival of sub-zero temperatures can be achieved by either avoiding or tolerating extracellular ice formation. Conflicting evidence has been presented showing that detached leaves of Arabidopsis thaliana are either freeze avoiding or tolerant. Here, we used three different natural Arabidopsis accessions from different habitats to investigate the frost resistance strategy of whole plants in soil. Plants were cooled to fixed temperatures or just held at their individual ice nucleation temperature for different time intervals. Tissue damage of whole plants was compared to the standard lethal temperature determined for detached leaves with external ice nucleation. While all detached leaves survived freezing when ice nucleation was externally initiated at mild sub-zero temperatures, whole plants of the southern accession behaved as freeze avoiding in the non-acclimated state. The northern accessions and all cold acclimated plants were freezing tolerant, but the duration of the freezing event affected tissue damage. Because this pointed to cell dehydration as mechanism of damage, the proportion of freezable water in leaves and osmolality of cell sap was determined. Indeed, the freezing tolerant accession Rsch had a lower proportion of freezable water and higher cell sap osmolality compared to the sensitive accession C24 in the cold acclimated state.


A multilevel analysis of neighbourhood built and social environments and adult self-reported physical activity and body mass index in Ottawa, Canada.
Canadian research examining the combined effects of social and built environments on physical activity (PA) and obesity is limited. The purpose of this study was to determine the relationships among built and social environments and PA and overweight/obesity in 85 Ottawa neighbourhoods. Self-reported PA, height and weight were collected from 3,883 adults using the International PA Questionnaire from the 2003-2007 samples of the Rapid Risk Factor Surveillance System. Data on neighbourhood characteristics were obtained from the Ottawa Neighbourhood Study; a large study of neighbourhoods and health in Ottawa. Two-level binomial logistic regression models stratified by sex were used to examine the relationships of environmental and individual variables with PA and overweight/obesity while using survey weights. Results identified that approximately half of the adults were insufficiently active or overweight/obese. Multilevel models identified that for every additional convenience store, men were two times more likely to be physically active (OR = 2.08, 95% CI: 1.72, 2.43) and with every additional specialty food store women were almost two times more likely to be overweight or obese (OR = 1.77, 95% CI: 1.33, 2.20). Higher green space was associated with a reduced likelihood of PA (OR = 0.93, 95% CI: 0.86, 0.99) and increased odds of overweight and obesity in men (OR = 1.10, 95% CI: 1.01, 1.19), and decreased odds of overweight/obesity in women (OR = 0.66, 95% CI: 0.44, 0.89). In men, neighbourhood socioeconomic scores, voting rates and sense of community belonging were all significantly associated with overweight/obesity. Intraclass coefficients were low, but identified that the majority of neighbourhood variation in outcomes was explained by the models. Findings identified that green space, food landscapes and social cohesiveness may play different roles on PA and overweight/obesity in men and women and future prospective studies are needed.


Synthesis and self-assembly of thio derivatives of calix[4]arene on noble metal surfaces.
Self-assembled monolayers (SAMs) provide a simple route to functionalize electrode surfaces with organic molecules. Herein we use cavity-containing derivatives of calix[4]arenes in SAMs. Bound to noble metal surface, the assembled molecules are candidates to serve as molecular sieves for H 2 molecules and H (+) ions, which could have relevance for fuel cell applications. Tetra- O-alkylated calix[4]arenes with thiolacetate and thiolamide wide-rim anchoring groups in cone and partial-cone conformations were designed, synthesized and self-assembled onto Au, Pt, and Pd surfaces. The resulting SAMs were systematically examined. Single crystal X-ray diffraction of 5,11,17,23-tetrakis(thioacetyl)-25,26,27,28-tetra- i-propoxycalix[4]arene confirmed the cone conformation and revealed the cavity dimensions of the SAMs that were formed by immersing noble metal substrates (Au, Pt and Pd deposited on Si-wafers) in solutions of calix[4]arenes. Surface characterization techniques including ellipsometry, cyclic voltammetry (CV) and X-ray photoelectron spectroscopy (XPS) were used, indicating that the metal surface is terminated with a monomolecular layer. Experimental thicknesses obtained from the ellipsometry are consistent with the calculated values. CV results showed 50 to 80% physical passivation against the Fe(CN) 6 (3-/4-) couple, implying an overall relatively low concentration of defects and pinholes in the films. The binding energies of the S2p core level in the XPS were consistent with the literature values and revealed that up to 3.2 out of four anchoring groups were bonded to the noble metal surface.


Stimuli-responsive magnetic nanomicelles as multifunctional heat and cargo delivery vehicles.
Hybrid nanoarchitectures are among the most promising nanotechnology-enabled materials for biomedical applications. Interfacing of nanoparticles with active materials gives rise to the structures with unique multiple functionality. Superparamagnetic iron oxide nanoparticles particles SPION are widely employed in the biology and in developing of advanced medical technologies. Polymeric micelles offer the advantage of multifunctional carriers which can serve as delivery vehicles carrying nanoparticles, hydrophobic chemotherapeutics and other functional materials and molecules. Stimuli-responsive polymers are especially attractive since their properties can be modulated in a controlled manner. Here we report on multifunctional thermo-responsive poly(N-isopropylacrylamide-co-acrylamide)-block-poly(ε-caprolactone) random block copolymer micelles as magnetic hyperthermia-mediated payload release and imaging agents. The combination of copolymers, nanoparticles and doxorubicin drug was tailored the way that the loaded micelles were cable to respond to magnetic heating at physiologically-relevant temperatures. A surface functionalization of the micelles with the integrin β4 antibody and consequent interfacing of the resulting nanobio hybrid with squamous head and neck carcinoma cells which is known to specifically over-express the A9 antigen resulted in concentration of the micelles on the surface of cells. No inherent cytotoxicity was detected for the magnetic micelles without external stimuli application. Furthermore, SPION-loaded micelles demonstrate significant MRI contrast enhancement abilities.


Competition of superconducting phenomena and Kondo screening at the nanoscale.
Magnetic and superconducting interactions couple electrons together to form complex states of matter. We show that, at the atomic scale, both types of interactions can coexist and compete to influence the ground state of a localized magnetic moment. Local spectroscopy at 4.5 kelvin shows that the spin-1 system formed by manganese-phthalocyanine (MnPc) adsorbed on Pb(111) can lie in two different magnetic ground states. These are determined by the balance between Kondo screening and superconducting pair-breaking interactions. Both ground states alternate at nanometer length scales to form a Moiré-like superstructure. The quantum phase transition connecting the two (singlet and doublet) ground states is thus tuned by small changes in the molecule-lead interaction.


Structural characterisation and comparison of the native and A-states of equine lysozyme.
Native state 1H NMR resonance assignments for 125 of the 129 residues of equine lysozyme have enabled measurement of the hydrogen exchange kinetics for over 60 backbone amide and three tryptophan indole hydrogen atoms in the native state. Native holo equine lysozyme hydrogen exchange protection factors are as large as 10(6), the most protected residues being located in elements of secondary structure. High exchange protection in the domain interface correlates with the binding of Ca2+ in this region. Equine lysozyme differs from most non-Ca2+ binding lysozymes in forming a highly populated partially folded state at low pH. The protein in this A-state at pH 2.0 has been found to bind 1-anilino-naphthalene-8-sulphonate with the enhancement of fluorescent intensity and blue shift in the spectral maximum characteristic of molten globules. NMR spectra indicate that the A-state is globally much less ordered than native equine lysozyme but does not contain significant regions of random coil structure. The amides most protected against hydrogen exchange in the A-state (protection factors up to 10(2) at 5 degrees C) correspond to residues of three of the four alpha-helices of the native state; the side-chains of these residues form a hydrophobic cluster that includes five aromatic residues. Circular dichroism and tryptophan fluorescence indicate that these residues are substantially more constrained than similar residues in "classical" molten globules. Taken together, the data suggest a model for the A-state of equine lysozyme in which a more ordered core is surrounded by a less ordered but still compact polypeptide chain.


Antiproliferative and Proapoptotic Effects of Crocin Combined with Hyperthermia on Human Breast Cancer Cells.
We investigated the suppressive effects of crocin alone and in combination with hyperthermia (HT) on proliferation of breast cancer cells. Cell viability, colony formation ability, and apoptosis were assessed by 3-(4,5-dimetylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT), soft agar, Hoechst 33258 staining, and percentage of lactate dehydrogenase (LDH) release methods, respectively. The mRNA levels Hsp27, Hsp70, Hsp90, Bax, and Bcl-2 were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Hsp70 and Hsp90 proteins were determined using enzyme-linked immunosorbent assay (ELISA) technique. Crocin in combination with HT significantly inhibited the proliferation of cancer cells in a dose- and time-dependent manner. There was a degree of synergism in the combined treatment. However, crocin did not show the high cytotoxic effect on normal cells. This treatment decreased colony formation of cancer cells up to 94%. Changed nuclear morphology and increased LDH indicated that crocin combined with HT has a more apoptotic effect than crocin alone. Furthermore, in treated cells Bax/Bcl-2 ratio markedly increased, whereas expression of heat-induced genes decreased. Also, the Hsp70 and Hsp90 proteins decreased in the treated cells. Our study indicated that combination of crocin and HT has strong antiproliferative and apoptotic activities against breast cancer cells. Hence, it is suggested that more studies are warranted to apply crocin as a possible, safe, and promising anticancer agent in cancer.


Self-Talk and Sports Performance: A Meta-Analysis.
Based on the premise that what people think influences their actions, self-talk strategies have been developed to direct and facilitate human performance. In this article, we present a meta-analytic review of the effects of self-talk interventions on task performance in sport and possible factors that may moderate the effectiveness of self-talk. A total of 32 studies yielding 62 effect sizes were included in the final meta-analytic pool. The analysis revealed a positive moderate effect size (ES = .48). The moderator analyses showed that self-talk interventions were more effective for tasks involving relatively fine, compared with relatively gross, motor demands, and for novel, compared with well-learned, tasks. Instructional self-talk was more effective for fine tasks than was motivational self-talk; moreover, instructional self-talk was more effective for fine tasks rather than gross tasks. Finally, interventions including self-talk training were more effective than those not including self-talk training. The results of this study establish the effectiveness of self-talk in sport, encourage the use of self-talk as a strategy to facilitate learning and enhance performance, and provide new research directions.


Acute effects of nitric oxide and cyclic GMP on human myocardial contractility.
Evidence that the activity of nitric oxide synthase and the generation of nitric oxide (NO) within the myocardium are enhanced in several cardiovascular disorders is increasing. Findings whether NO exerts a direct effect on cardiac contractility are contradictory. Therefore, the direct effect of the NO donor sodium nitroprusside (SNP) on isometric force of contraction of human atrial and ventricular myocardium was investigated, and the question was addressed whether the effects of NO on cardiac contractility are mediated via cGMP. Experiments were performed on isolated electrically driven (1 Hz, 37 degrees C) human right atrial trabecula and left ventricular papillary muscle preparations from nonfailing and terminally failing hearts. SNP led to a concentration-dependent decrease of force of contraction (FOC) with a maximum effect at 100 micromol/l. In atrial trabecula, SNP (100 micromol/l) caused an acute decrease in basal FOC as well as in FOC after application of isoprenaline or IBMX by 12.5 +/- 5% (P < .05), 16.6 +/- 3.7% (P < .05) and 18.3 +/- 4.2% (P < .05), respectively. The negative inotropic effects could be attenuated by the guanylyl cyclase inhibitor methylene blue. In papillary muscle preparations, NO release caused a maximum decrease in basal and in isoprenaline-enhanced FOC of 11.0 +/- 1.9% (P < .05) and 23.6 +/- 1.5% (P < .05), respectively. In the presence of isoprenaline, the reduction of FOC was less pronounced in failing than in nonfailing papillary muscles. 8-bromo-cGMP caused a 38.2 +/- 5.2% decrease in atrial trabecula contractility. Both SNP and 8-bromo-cGMP caused a shortening of the contractile twitch with a premature onset of relaxation. As determined by radioimmunoassay, exposure of atrial trabecula to SNP (100 micromol) led to a 6-fold increase in myocardial cGMP concentrations, which could be attenuated by methylene blue. In conclusion, NO exerts a negative inotropic effect on human atrial and ventricular myocardium which seems to be mediated via generation of cGMP. The release of NO within the myocardium in a variety of cardiovascular disorders might explain decreases in cardiac contractility. The control of NO release could be an important target for future therapeutical interventions in these pathological conditions.


[Determination of Fe, Al, Ca, Ti, P and Cu in silicon metal by XRF].
This article puts forward a sample preparation method that first dissolve the sample by acid and evaporate the solution then melt the remains by flux. This method resolves the problem that silicon metal can't easy to prepare sample by fusion, and it can determine several elements in the sample simultaneously. This method overcomes the limit of standard sample and removes the matrix effects. The range of determination is wide and the results is accurate. The condition of preparing sample was confirmed by test.


Identifying phenotype-associated subpopulations through LP_SGL.
Single-cell RNA sequencing (scRNA-seq) enables the resolution of cellular heterogeneity in diseases and facilitates the identification of novel cell types and subtypes. However, the grouping effects caused by cell-cell interactions are often overlooked in the development of tools for identifying subpopulations. We proposed LP_SGL which incorporates cell group structure to identify phenotype-associated subpopulations by integrating scRNA-seq, bulk expression and bulk phenotype data. Cell groups from scRNA-seq data were obtained by the Leiden algorithm, which facilitates the identification of subpopulations and improves model robustness. LP_SGL identified a higher percentage of cancer cells, T cells and tumor-associated cells than Scissor and scAB on lung adenocarcinoma diagnosis, melanoma drug response and liver cancer survival datasets, respectively. Biological analysis on three original datasets and four independent external validation sets demonstrated that the signaling genes of this cell subset can predict cancer, immunotherapy and survival.


Basolateral amygdala lesions and sensitivity to reinforcer magnitude in concurrent chains schedules.
Previous studies show that the basolateral amygdala (BLA) is required for behavior to adjust when the value of a reinforcer decreases after satiation or pairing with gastric distress. This study evaluated the effect of pre- or post-training excitotoxic lesions of the BLA on changes in preference with another type of contingency change, reinforcer magnitude reversal. Rats were trained to press left and right levers during a variable-interval choice phase for 50 microl or 150 microl sucrose delivered to consistent locations after a 16-s delay. Tones were presented during the first and last 2s of the delay to reinforcement. The tone frequency predicted the magnitude of sucrose reinforcement in baseline conditions. All groups acquired stable preference for the lever on the large (150 microl) reinforcer side. However, nose poking during the delay to large reinforcement was highly accurate (i.e., to the reinforced side) for all groups except the rats with BLA lesions induced before training, suggesting impaired control of behavior by the tone. After the acquisition of stable preference, the locations of the reinforcer magnitudes were unpredictably reversed for a single session. Pre-training lesions blunted changes in preference when the reinforcer magnitudes were reversed. Lesions induced after stable preference was acquired, but prior to reversal, did not disrupt changes in preference. The data suggest that the BLA contributes to the adaptation of choice behavior following changes in reinforcer magnitude. Impaired learning about the tone-reinforcer magnitude relationships may have disrupted discrimination of the reinforcer magnitude reversal.


Introduction of the conducted electrical weapon into a hospital setting.
The TASER(®) X26 Conducted Electrical Weapon (CEW) provides painful stimuli and neuromuscular incapacitation to potentially violent persons. Use by law enforcement in society is common. Presenting a CEW is known to de-escalate some situations. Health care personnel sometimes encounter violent persons within the confines of the hospital. CEW use by health care security personnel has not been described. The objective is to describe results from the introduction of the CEW into a hospital environment. Upon introducing the CEW into an urban hospital campus, standardized reports were made describing all CEW use by hospital security. Reports were retrospectively reviewed for the first 12 months of CEW use. Collected data included force options used, potential injuries avoided, witness comments, outcomes, and whether the CEW required full activation or if inactive presentation was sufficient to control the situation. Rates of security personnel injuries were also gathered. Descriptive analysis was applied. Twenty-seven CEW deployments occurred: four were inactive presentation, 20 were presentation with LASER sight activation, and three were probe deployments with a 5-s delivery of electrical current. Two persons required evaluation for minor injuries not related to CEW use. Witnesses reported that in all incidents, injuries were likely avoided due to CEW presentation or use. CEW use aborted one suicide attempt. Personnel injury rates decreased during the study period. CEW introduction into a health care setting demonstrated the ability to avert and control situations that could result in further injury to subjects, patients, and personnel. This correlates with a decrease in injury for hospital personnel. Further study is recommended for validation.


Effect of myelin basic protein on the thermotropic behavior of aqueous dispersions of neutral and anionic glycosphingolipids and their mixtures with dipalmitoylphosphatidylcholine.
The thermotropic behavior of the natural glycosphingolipids galactosylceramide, asialo-Gal beta 1-3GalNAc beta 1-4Gal(3-2 alpha NeuAc)beta 1-4Glc beta 1-Cer (GM1), sulfatide, GM1, NeuAc alpha 2-3Gal beta 1-3GalNAc beta 1-4Gal(3-2 alpha NeuAc)beta 1-4Glc beta 1-1Cer (GD1a), and NeuAc alpha 2-3Gal beta 1-3GalNAc beta 1-4Gal(3-2 alpha NeuAc8-2 alpha NeuAc)beta 1-4Glc beta 1-1 Cer (GT1b), and their mixtures with dipalmitoylphosphatidylcholine (DPPC) in the presence of myelin basic protein (MBP) was studied by high sensitivity differential scanning calorimetry. The transition temperature of DPPC, galactosylceramide, and asialo-GM1 is affected little by MBP while their transition enthalpy is decreased in proportion to the amount of protein in the mixture. The thermotropic behavior of anionic glycosphingolipids is considerably perturbed by MBP. The transition temperature of gangliosides increases in the presence of MBP, whereas that of sulfatide decreases. The enthalpy of the transition of anionic glycosphingolipids increases markedly in the presence of MBP. The excess heat capacity function of these systems can be resolved into two independent phase transitions. Phase separation of enriched lipid/protein domains occurs in a magnitude that depends on the amount of MBP; the rest of the lipid phase exhibits some altered thermodynamic properties. In mixtures of glycosphingolipids with DPPC, phase separation is also present but no phase transition with the characteristic of pure DPPC is found. MBP is changing the properties of the lipid mixture as a whole and does not interact exclusively with the glycosphingolipids. The proportion of MBP required to produce the maximal changes is greater the greater the complexity of the glycosphingolipids polar head group. Relatively small variations of the amount of MBP induce large shifts in the proportion of the different phases present.


Metabolic complications of androgen deprivation therapy for prostate cancer.
Androgen deprivation therapy has a variety of well recognized adverse effects including vasomotor flushing, loss of libido, fatigue, gynecomastia, anemia and osteoporosis. This review focuses on the more recently described metabolic complications of androgen deprivation therapy including obesity, insulin resistance and lipid alterations as well as the association of androgen deprivation therapy with diabetes and cardiovascular disease. We reviewed the medical literature using the PubMed® search terms prostate cancer, androgen deprivation therapy, gonadotropin-releasing hormone agonists, obesity, insulin resistance, lipids, diabetes, cardiovascular disease and myocardial infarction. We provide a focused review and our perspective on the relevant literature. Androgen deprivation therapy decreases lean mass and increases fat mass. It also decreases insulin sensitivity while increasing low density lipoprotein cholesterol, high density lipoprotein cholesterol and triglycerides. Consistent with these adverse metabolic effects, androgen deprivation therapy may be associated with a greater incidence of diabetes and cardiovascular disease. Some of these androgen deprivation therapy related metabolic changes (obesity, insulin resistance and increased triglycerides) overlap with features of the metabolic syndrome. However, in contrast to the metabolic syndrome, androgen deprivation therapy increases subcutaneous fat and high density lipoprotein cholesterol. Androgen deprivation therapy increases obesity, decreases insulin sensitivity and adversely alters lipid profiles. It may be associated with a greater incidence of diabetes and cardiovascular disease. The benefits of androgen deprivation therapy should be weighed against these and other potential harms. Little is known about the optimal strategy to mitigate the adverse metabolic effects of androgen deprivation therapy. Thus, we recommend an emphasis on existing strategies for screening and treatment that have been documented to reduce the risk of diabetes and cardiovascular disease in the general population.


Simultaneous quantitative determination of amphetamines, ketamine, opiates and metabolites in human hair by gas chromatography/mass spectrometry.
A gas chromatography/mass spectrometry (GC/MS) method was developed and validated for the determination of common drugs of abuse in Asia. The method was able to simultaneously quantify amphetamines (amphetamine; AP, methamphetamine; MA, methylenedioxy amphetamine; MDA, methylenedioxymeth mphetamine; MDMA, methylenedioxy ethylamphetamine; MDEA), ketamine (ketamine; K, norketamine; NK), and opiates (morphine; MOR, codeine; COD, 6-acetylmorphine; 6-AM) in human hair. Hair samples (25 mg) were washed, cut, and incubated overnight at 25 degrees C in methanol/trifluoroacetic acid (methanol/TFA). The samples were extracted by solid-phase extraction (SPE), derivatized using heptafluorobutyric acid anhydride (HFBA) at 70 degrees C for 30 min, and the derivatives were analyzed by electron ionization (EI) GC/MS in selected ion monitoring mode. Confirmation was accomplished by comparing retention times and the relative abundances of selected ions with those of standards. Deuterated analogs of the analytes were used as internal standards for quantification. Calibration curves for ten analytes were established in the concentration range 0.1-10 ng/mg with high correlation coefficients (r2 > 0.999). The intra-day and inter-day precisions were within 12.1% and 15.8%, respectively. The intra-day and inter-day accuracies were between -8.7% and 10.7%, and between -5.9% and 13.8%, respectively. The limit of detection (LOD) and limit of quantification (LOQ) obtained were 0.03 and 0.05 ng/mg for AP, MA, MDA, MDMA and MDEA; 0.05 and 0.08 ng/mg for K, NK, MOR and COD; and 0.08 and 0.1 ng/mg for 6-AM. The recoveries were above 88.6% for all the compounds, except K and NK which were in the range of 71.7-72.7%. Eight hair samples from known polydrug abusers were examined by this method. These results show that the method is suitable for broad-spectrum drug testing in a single hair specimen.


Obesity and immune cells in Saudi females.
For the past two decades or more, obesity has been increasing in industrialized and affluent countries. This increase has been shown in children, adults and the elderly. The latest statistical studies in Saudi Arabia show that obesity is increasing, with obese Saudi women outnumbering obese Saudi males, and that these numbers are continuously rising. Obesity, which leads to many medical risks, affects the immune system in direct and indirect ways. In this study, the effect of obesity on the immune system of 119 Saudi female university students was investigated. Using a blood sample from each subject, the following immune-related parameters were determined: total and differential white blood cell counts (WBCs), total lymphocyte and sub-lymphocyte cell counts. Two measures of body fat were used: the body mass index (BMI) and the waist-to-hip ratio (WHR) to correlate body weight to the other measured parameters. A significant correlation was present between BMI and WHR each with total white blood cells, neutrophils, and CD4 lymphocyte concentrations. Some other parameters were only affected by the increase in the BMI but not the WHR, such as platelets, while others were affected by the WHR only, such as total T-cells. On the other hand, there were no significant correlations between BMI or WHR and basophil, eosinophil, monocyte, CD8, B-cell, and NK-cell counts. The findings indicate that obesity might seriously affect the innate and adaptive immune systems.


Should AMOC observations continue: how and why?
The Atlantic meridional overturning circulation (AMOC) is a large-scale circulation pattern responsible for northward heat transport in the Atlantic and is associated with climate variations on a wide range of time scales. Observing the time-varying AMOC has fundamentally changed our understanding of the large-scale ocean circulation and its interaction with the climate system, as well as identified shortcomings in numerical simulations. With a wide range of gains already achieved, some now ask whether AMOC observations should continue. A measured approach is required for a future observing system that addresses identified gaps in understanding, accounts for shortcomings in observing methods and maximizes the potential to guide improvements in ocean and climate models. Here, we outline a perspective on future AMOC observing and steps that the community should consider to move forward. This article is part of a discussion meeting issue 'Atlantic overturning: new observations and challenges'.


A method for determining the optimum supporting opportunity of roadway based on energy dissipation.
The time and space of the support structure applying is related to the overall stability of the roadway after excavation directly. Designed twenty-four groups of roadway support schemes with time and space dimensions, and studied the stability characteristics of roadway in different schemes by using Fast Lagrangian Analysis of Continua in Three Dimensions. The main conclusions are as follows: the influence of energy dissipation (time) and support position (space) on the stability of the roadway is not a linear relationship, and supporting at the appropriate opportunity can be beneficial. Established the "displacement-dissipation energy" curve, founding that there is an obvious "jump" phenomenon in the dissipation energy of surrounding rock during the process of gradually increasing displacement. A novel method for determining the optimum supporting opportunity of roadway based on energy dissipation was proposed, based on the above finding. This study can provide an original idea for the determination of roadway supporting opportunity.


Early recognition and management of maternal sepsis in Pakistan: a feasibility study of the implementation of FAST-M intervention.
Maternal sepsis is the third leading cause of maternal mortality globally. WHO and collaborators developed a care bundle called FAST-M (Fluids, Antibiotics, Source identification and treatment, Transfer and Monitoring) for early identification and management of maternal sepsis in low-resource settings. This study aimed to determine feasibility of FAST-M intervention in a low-resource setting in Pakistan. The FAST-M intervention consists of maternal sepsis screening tools, treatment bundle and implementation programme. A feasibility study with before and after design was conducted in women with suspected maternal sepsis admitted at the Liaquat University of Medical and Health Sciences hospital Hyderabad. The study outcomes were compared between baseline and intervention phases. In the baseline phase (2 months), the existing sepsis care practices were recorded, followed by a training programme for healthcare providers on the application of FAST-M tools. These tools were implemented in the intervention phase (4 months) to assess any change in clinical practices compared with the baseline phase. During the FAST-M implementation, 439 women were included in the study. 242/439 were suspected maternal infection cases, and 138/242 were women with suspected maternal sepsis. The FAST-M bundle was implemented in women with suspected maternal sepsis. Following the FAST-M intervention, significant changes were observed. Improvements were seen in the monitoring of oxygen saturation measurements (25.5% vs 100%; difference: 74%; 95% CI: 68.4% to 80.5%; p<0.01), fetal heart rate assessment (58% vs 100%; difference: 42.0%; 95% CI: 33.7% to 50.3%; p≤0.01) and measurement of urine output (76.5% vs 100%; difference: 23.5%; 95% CI: 17.6% to 29.4%; p<0.01). Women with suspected maternal sepsis received all components of the treatment bundle within 1 hour of sepsis recognition (0% vs 70.5%; difference: 70.5%; 95% CI: 60.4% to 80.6%; p<0.01). Implementation of the FAST-M intervention was considered feasible and enhanced early identification and management of maternal sepsis at the study site. ISRCTN17105658.


Applications of ion beam analysis to calcified tissue research.
Various nondestructive ion beam analysis techniques have been developed and applied to study the concentrations of fluorine and other trace elements in calcified tissues.Fluorine has been determined by prompt gamma activation analysis through the F(ϱ,αγ)O reaction. This method is quick, convenient, and sensitive, and can also be applied to measure fluorine depth distribution nondestructively in teeth and bone samples. By the application of this technique, fluorine concentrations have been determined in a number of teeth with known histories and bones of experimental animals. Moreover, F-depth-distributions to 10-μm depths have also been obtained in a number of selected human and animal teeth.Carbon was measured by activation analysis with He-3 ions, and the technique of Proton-Induced X-ray Emission (PIXE) has been developed to simultaneously determine Ca, P, and trace elements in well-documented teeth. Dental hard tissues, i.e., enamel, dentine, cementum, and their junctions, as well as different parts of the same tissue, have been examined separately. A number of elements, Na, Mg, Al, P, Cl, Ca, Cr, Mn, Fe, Ni, Cu, Zn, Sr, Br, Rb and Pb, have been determined in these dental tissues. The concentrations of some of these elements vary considerably in different teeth and in various parts of the same tooth.The special advantages of these nuclear techniques for studying metabolic bone diseases, renal diseases, and the effect of Pb on childrens' intelligence are discussed.


Dying by default, the biology of apoptosis: a review.
Apoptosis differs from necrosis in that no inflammatory changes occur. The understanding of apoptosis was greatly improved by the discovery of a natural model of apoptosis in Caenorhabditis elegans, a nematode worm. The study of this worm led to the discovery of two sets of genes, the prosuicide genes and the antisuicide genes which control apoptosis. Apoptosis is an active process that involves w activation of specific enzymes. The understanding of the molecular biology of apoptosis may in future lead to the availability of a potent weapon to use against cancer and to modify cell death that occurs in the neurodegenerative disorders.


Heterologous envelope immunogens contribute to AIDS vaccine protection in rhesus monkeys.
Because a strategy to elicit broadly neutralizing anti-human immunodeficiency virus type 1 (HIV-1) antibodies has not yet been found, the role of an Env immunogen in HIV-1 vaccine candidates remains undefined. We sought to determine whether an HIV-1 Env immunogen genetically disparate from the Env of the challenge virus can contribute to protective immunity. We vaccinated Indian-origin rhesus monkeys with Gag-Pol-Nef immunogens, alone or in combination with Env immunogens that were either matched or mismatched with the challenge virus. These animals were then challenged with a pathogenic simian-human immunodeficiency virus. The vaccine regimen included a plasmid DNA prime and replication-defective adenoviral vector boost. Vaccine regimens that included the matched or mismatched Env immunogens conferred better protection against CD4(+) T-lymphocyte loss than that seen with comparable regimens that did not include Env immunogens. This increment in protective immunity was associated with anamnestic Env-specific cellular immunity that developed in the early days following viral challenge. These data suggest that T-lymphocyte immunity to Env can broaden the protective cellular immune response to HIV despite significant sequence diversity of the strains of the Env immunogens and can contribute to immune protection in this AIDS vaccine model.


Alterations in retinal nerve fiber layer thickness in early stages of diabetic retinopathy and potential risk factors.
To investigate the loss of retinal nerve fiber layer (RNFL) in type-2 diabetic patients with early-stage diabetic retinopathy (DR) and to identify potential risk factors accounting for these alterations. In this cross-sectional study, 158 type-2 diabetic patients were divided into three groups based on their DR status. RNFL thickness and other optic disc parameters were obtained by optical coherence tomography (OCT) and then compared among different groups. We investigated the potential association between RNFL loss and systemic risk factors for DR, including diabetes duration, body mass index (BMI), serum lipids, hemoglobin A1c (HbA1c) and albumin-creatinine ratio (ACR). One-way ANOVA was carried out to compare RNFL thickness among different groups, Pearson correlation and multivariate linear regression analysis were performed to determine potential risk factors related to RNFL thickness in these patients. There were significant differences in the average (F = 8.872, P = 0.003), superior (F = 8.769, P = 0.004), and inferior (F = 8.857, P = 0.003) RNFL thickness of both eyes among the groups, but no obvious difference in optic disc parameters was found. Diabetic duration, BMI, TG, High density lipoprotein cholesterol (HDL), HbA1c, and ACR were found negatively related to the RNFL thickness in both or single eye according to Pearson correlation analysis. After controlling for age, gender, and axis length (AL) in multivariate linear regression analysis, the diabetic duration was associated significantly with RNFL thickness of superior in both eye (right eye: p = 0.016, left eye: p = 0.024), BMI was related to the nasal quadrant of the right eye (p = 0.034), and TG was related to the inferior of the right eye (p = 0.037), HbA1c (p = 0.026) was associated significantly with the average RNFL thickness of the right eye. In addition, ACR was found negatively related to average (p = 0.042) and inferior quadrant (p = 0.014) of the left eye, respectively. RNFL loss might be the earliest structural change of retina in diabetic patients, and associated with diabetic duration, BMI, TG, HbA1c, and ACR. The conclusions of this study need to be proved by other well-matched and large-scale prospective clinical trials in the future, because the correlations discovered in our study were weak.


Guiding femoral rotational growth in an animal model.
Guided growth is most commonly utilized about the knee and ankle for the correction of coronal-plane deformities by the use of plates positioned perpendicular to the physis. Sagittal-plane deformity correction has been described as well. The purpose of our study was to examine the ability to affect axial-rotational growth. Our hypothesis was that placement of plates in an oblique orientation relative to the physis can induce rotational growth deformity. Our hypothesis was tested with use of a mathematical model and a bone model and subsequently in a rabbit model. Thirteen six-week-old rabbits underwent a rotational guided growth procedure involving the distal aspect of the right femur, with a sham procedure performed on the left side. Two plates were positioned in an oblique orientation relative to the physis, medially and laterally, to guide either internal or external rotational growth. After the rabbits were killed six weeks after the surgery, the femoral rotational profile was assessed by computed tomography scans of the dissected femora and the growth plates were examined histologically. A significant effect on the rotational profile was found in the treated femora. When the plates were positioned to guide external rotation, the rotational profile was significantly greater in the treated femora (29.0° compared with 11.3° in the sham femora; p = 0.008). There was a positive linear correlation between the right-left difference in rotational profile and the change in inter-plate angle (R2 = 0.72, p = 0.001). Every 1° of inter-plate angle change induced 0.367° of rotational profile difference (p = 0.001). Histologically, a swirling effect of the physeal cell columns was seen in the treated femora. Guided growth using plates was demonstrated to alter axial-rotational growth in a predictable fashion in a rabbit model. Guided growth using plates may be effective for correction of rotational and multiplanar deformities.


A green energy research: forecasting of wind power for a cleaner environment using robust hybrid metaheuristic model.
Wind is a stochastic and intermittent renewable energy source. Due to its nature, it is extremely hard to forecast wind power. Accurate wind power forecasting can be encouraging and motivating for investors to shed light on future uncertainties caused by global warming. Thus, CO2 and other greenhouse gases (GHG) which are harmful to the environment will not be released into the atmosphere, while generating electrical energy. This paper presents a novel precise, fast and powerful hybrid metaheuristic wind power forecasting approach based on statistical and mathematical data from real weather stations. The model was developed as a hybrid metaheuristic algorithm based on artificial neural networks (ANNs), particle swarm optimization (PSO) and radial movement optimization (RMO). Real-time wind data was gathered from wind measuring stations (WMS) at two separate places in Burdur and Osmaniye cities, Turkey. The key contribution of this new model is the ability to perform wind power forecasting studies, without needing wind speed data, with high accuracy and rapid solutions. Also, wind power forecasting studies with high accuracy have been carried out despite the height differences between the sensors. That is, for WMS-1 and WMS-2, it has succeeded the wind power forecasting at 61 m and 60.3 m using temperature (3 m), humidity (3 m) and pressure (3.5 m) data. The performance results were presented in tables and graphs.


Mutations in HA and PA affect the transmissibility of H7N9 avian influenza virus in chickens.
Low pathogenic (LP) H7N9 avian influenza virus (AIV) emerged in 2013 and had spread widely over several months in China, experienced a noteworthy reduction in isolation rate in poultry and human since 2017. Here, we examined the transmission of H7N9 viruses to better understand viral spread and dissemination mechanisms. Three out of four viruses (2013-2016) could transmit in chickens through direct contact, and airborne transmission was confirmed in the JT157 (2016) virus. However, we did not detect the transmission of the two 2017 viruses, WF69 and AH395, through either direct or airborne exposure. Molecular analysis of genome sequence of two viruses identified eleven mutations located in viral proteins (except for matrix protein), such as PA (K362R and S364N) and HA (D167N, H7 numbering), etc. We explored the genetic determinants that contributed to the difference in transmissibility of the viruses in chickens by generating a series of reassortants in the JT157 background. We found that the replacement of HA gene in JT157 by that of WF69 abrogated the airborne transmission in recipient chickens, whereas the combination of HA and PA replacement led to the loss of airborne and direct contact transmission. Failure with contact transmission of the viruses has been associated with the emergence of the mutations D167N in HA and K362R and S364N in PA. Furthermore, the HA D167N mutation significantly reduced viral attachment to chicken lung and trachea tissues, while mutations K362R and S364N in PA reduced the nuclear transport efficiency and the PA protein expression levels in both cytoplasm and nucleus of CEF cells. The D167N substitution in HA reduced the H7N9 viral acid stability and avian-like receptor binding, while enhanced human-like receptor binding. Further analysis revealed these mutants grew poorly in vitro and in vivo. To conclude, H7N9 AIVs that contain mutations in the HA and PA protein reduced the viral transmissibility in chicken, and may pose a reduced threat for poultry but remain a heightened public health risk.


Significance of long chain polyunsaturated fatty acids in human health.
In the last decades, the development of new technologies applied to lipidomics has revitalized the analysis of lipid profile alterations and the understanding of the underlying molecular mechanisms of lipid metabolism, together with their involvement in the occurrence of human disease. Of particular interest is the study of omega-3 and omega-6 long chain polyunsaturated fatty acids (LC-PUFAs), notably EPA (eicosapentaenoic acid, 20:5n-3), DHA (docosahexaenoic acid, 22:6n-3), and ARA (arachidonic acid, 20:4n-6), and their transformation into bioactive lipid mediators. In this sense, new families of PUFA-derived lipid mediators, including resolvins derived from EPA and DHA, and protectins and maresins derived from DHA, are being increasingly investigated because of their active role in the "return to homeostasis" process and resolution of inflammation. Recent findings reviewed in the present study highlight that the omega-6 fatty acid ARA appears increased, and omega-3 EPA and DHA decreased in most cancer tissues compared to normal ones, and that increments in omega-3 LC-PUFAs consumption and an omega-6/omega-3 ratio of 2-4:1, are associated with a reduced risk of breast, prostate, colon and renal cancers. Along with their lipid-lowering properties, omega-3 LC-PUFAs also exert cardioprotective functions, such as reducing platelet aggregation and inflammation, and controlling the presence of DHA in our body, especially in our liver and brain, which is crucial for optimal brain functionality. Considering that DHA is the principal omega-3 FA in cortical gray matter, the importance of DHA intake and its derived lipid mediators have been recently reported in patients with major depressive and bipolar disorders, Alzheimer disease, Parkinson's disease, and amyotrophic lateral sclerosis. The present study reviews the relationships between major diseases occurring today in the Western world and LC-PUFAs. More specifically this review focuses on the dietary omega-3 LC-PUFAs and the omega-6/omega-3 balance, in a wide range of inflammation disorders, including autoimmune diseases. This review suggests that the current recommendations of consumption and/or supplementation of omega-3 FAs are specific to particular groups of age and physiological status, and still need more fine tuning for overall human health and well being.


Second-generation hormonotherapy in prostate cancer and bone microenvironment.
Prostate cancer (Pca) is the most commonly diagnosed cancer affecting men in France. Before the age of 75 years old, 1 in 8 French men will have Pca. Androgen deprivation therapies (ADT) remain the standard of care. Such therapies induce significant bone loss. The bone-remodelling cycle depends on the androgen synthesis signalling pathways. Furthermore, age-specific hormonal decline plays a key role in the decrease in bone mass. As a result, the older the patients, the more likely they are to have osteoporosis if they are treated with hormone therapy. Their risk of osteoporotic fracture has an impact on their quality of life and their capacity of independent living. In recent years, newer hormone therapies (acetate abiraterone, enzalutamide, apalutamide and darolutamide) have proved efficient in metastatic castration-resistant Pca (mCRPC) patients as well as in hormone naïve patients, and actually in nonmetastatic diagnosis. The combination of these treatments with ADT highly inhibit androgen production pathways. They are prescribed to aged patients undergoing bone density loss after first-generation antiandrogen treatment. Specific recommendations for bone health management in Pca patients are currently lacking. To date, bone mineral density in patients treated with second-generation hormone therapy has never been assessed in a prospective study. This review aims at reviewing what is known about the impact of second-generation hormonotherapy on bone microenvironment.


Misonidazole-induced chemopotentiation of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea toxicity in O6-methylguanine-DNA methyltransferase proficient (Mer+) and deficient (Mer-) cell lines.
The radiation sensitizing agent misonidazole (MISO) was combined with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) for the treatment of Mer+ (IMR-90, HeLa, and HeLa-S3) and Mer- (EMT-6/Ro, VA-13, and HeLa-MR) cell lines under hypoxic conditions in vitro. The magnitude of enhancement achieved by the addition of MISO was calculated by comparison with survival curves obtained by treating each cell line with CCNU alone, under hypoxic conditions. As expected, the Mer+ cells were more resistant to CCNU treatment than were their Mer- counterparts. In the presence of 1.0 mM MISO the toxicity of CCNU was enhanced (dose enhancement factor, 1.4-1.6) in all three of the Mer- lines. However, the Mer+ lines were less responsive to chemopotentiation by MISO. The toxicity of CCNU toward two of the Mer+ lines, IMR-90 and HeLa, was not modified by the addition of MISO, while a slight enhancement (dose enhancement factor, 1.2) was observed in the HeLa-S3 line. Similar results were obtained with IMR-90 and VA-13 cells treated by postincubation in which aerobic CCNU treatment was followed by hypoxic exposure to MISO for up to 6 h. While no correlation was observed between Mer status and the hypoxic toxicity of MISO, the data suggest that a relationship might exist between chemopotentiation and MISO sensitivity when each phenotype is considered separately. These observations suggesting that tumor cells of the Mer+ phenotype may be less responsive to MISO chemopotentiation have significant implications for ongoing and planned clinical trials designed to evaluate the potential of chemopotentiation using CCNU and MISO since greater than 75% of human tumors are Mer+.


Effects of taurocholate infusion on biliary excretion in isolated perfused rat livers. Decreased biliary excretion of dibromosulfophthalein in pregnancy.
A crossover experimental design was used to examine the effects of saline (SAL) vs. taurocholate (TC) infusion on hepatic excretory function in isolated perfused livers from pregnant (19-21 days gestation) and nonpregnant female rats. Bile flow, bile acid concentration, bile acid secretory rate, dibromosulfophthalein (DBSP) concentration in bile, and DBSP secretory rates were determined in livers infused continuously with DBSP and initially with SAL (1 ml/hr, 45 min), followed by TC (60 mumol/hr, 1 ml/hr; 75 min) or initially with TC (45 min) followed by SAL (75 min). The order of infusion (SAL-TC vs. TC-SAL) had no significant effect. TC infusion significantly increased all measures in livers from both nonpregnant and pregnant rats. Two-way analysis of variance followed by the Tukey-Kramer test showed that bile flow (microliter/min/g liver) and DBSP concentration in bile (mumol/ml) were significantly decreased during SAL infusions in pregnancy. These two measures plus bile acid and DBSP secretory rates (nmol/min/g liver) were also significantly decreased during TC infusion in pregnancy. Pregnancy had no effect on bile acid concentration in the presence of SAL or TC infusions. When bile flow, bile acid, and DBSP secretory rates were calculated per whole liver, only the DBSP secretory rate was significantly decreased in pregnancy. These data indicate that bile flow and bile acid secretion do not increase in proportion to the increase in liver weight in pregnancy so that these measures are decreased when expressed per g liver. Pregnancy appears to have a real inhibitory effect on DBSP since its secretion is depressed when activity is expressed per g liver or per whole organ.


A developmental perspective on the link between parents' employment and children's obesity.
Despite public concerns about the negative implications of the increased labor force participation of mothers for child development, decades of research have revealed few risks and some benefits. One potential risk-a consistently observed association between maternal employment and childhood obesity-offers a window into how some dimensions of family health may be undermined by work in an economic and policy context that is not family friendly. The purpose of this article is to identify ways that a developmental perspective can enrich the literature on how children's weight may be related to the work experiences of both mothers and fathers across diverse populations, a literature that heretofore has been dominated by economic and demographic perspectives, focused almost solely on women, and largely ignored racial/ethnic variation. After reviewing the extant literature, we put forward a conceptual model that uses ecological and developmental insights to identify the mechanisms by which parents' employment might matter to children's weight and discuss this model in the context of the contemporary landscape of family policy. (PsycINFO Database Record


Alteration in sensitivity to isoproterenol and acetylcholine in the rat heart after repeated administration of isoproterenol.
Alteration of sensitivity to the inotropic responses to isoproterenol and acetylcholine (ACh) and of saturation constants for the specific binding of [3H]dihydroalprenolol and [3H]quinuclidinyl benzilate to particulate fractions were investigated in rat hearts chronically treated with isoproterenol. The EC50 value for the inotropic response to isoproterenol in the atria of rats injected i.p. with isoproterenol (0.01 or 0.1 mg/kg) twice a day for 10 days, was 9.0-fold higher than in controls. Isoproterenol (0.17 mg/kg i.p.)-induced stimulation of cardiac ornithine decarboxylase activity was significantly (P less than .05) attenuated in atria from animals of the treated groups. Scatchard analysis of specific binding of [3H]dihydroalprenolol revealed that repeated isoproterenol injection produced a significant decrease in the maximum number of binding sites (Bmax), but not in the dissociation constant (KD) for this antagonist. In comparison to the isoproterenol-induced changes in beta adrenergic positive inotropic response, repeated treatment with isoproterenol decreased 2-fold the EC50 value for the negative inotropic response to ACh in isolated atria. Scatchard analysis of specific [3H]quinuclidinyl benzilate binding, however, indicated a significant (P less than .01) decrease in Bmax. Repeated isoproterenol injections also elicited a significant increase in cardiac weight. It is suggested that repeated administration of isoproterenol induces a decrease in density of beta adrenergic receptors which may in part underlie a cardiac hyposensitivity to isoproterenol and an increase in the number of muscarinic ACh receptors and inotropic responsiveness to ACh.


Generalizing common tasks in automated skin lesion diagnosis.
We present a general model using supervised learning and MAP estimation that is capable of performing many common tasks in automated skin lesion diagnosis. We apply our model to segment skin lesions, detect occluding hair, and identify the dermoscopic structure pigment network. Quantitative results are presented for segmentation and hair detection and are competitive when compared to other specialized methods. Additionally, we leverage the probabilistic nature of the model to produce receiver operating characteristic curves, show compelling visualizations of pigment networks, and provide confidence intervals on segmentations.


Conformational changes and substrate recognition in Pseudomonas aeruginosa D-arginine dehydrogenase.
DADH catalyzes the flavin-dependent oxidative deamination of d-amino acids to the corresponding α-keto acids and ammonia. Here we report the first X-ray crystal structures of DADH at 1.06 Å resolution and its complexes with iminoarginine (DADH(red)/iminoarginine) and iminohistidine (DADH(red)/iminohistidine) at 1.30 Å resolution. The DADH crystal structure comprises an unliganded conformation and a product-bound conformation, which is almost identical to the DADH(red)/iminoarginine crystal structure. The active site of DADH was partially occupied with iminoarginine product (30% occupancy) that interacts with Tyr53 in the minor conformation of a surface loop. This flexible loop forms an "active site lid", similar to those seen in other enzymes, and may play an essential role in substrate recognition. The guanidinium side chain of iminoarginine forms a hydrogen bond interaction with the hydroxyl of Thr50 and an ionic interaction with Glu87. In the structure of DADH in complex with iminohistidine, two alternate conformations were observed for iminohistidine where the imidazole groups formed hydrogen bond interactions with the side chains of His48 and Thr50 and either Glu87 or Gln336. The different interactions and very distinct binding modes observed for iminoarginine and iminohistidine are consistent with the 1000-fold difference in k(cat)/K(m) values for d-arginine and d-histidine. Comparison of the kinetic data for the activity of DADH on different d-amino acids and the crystal structures in complex with iminoarginine and iminohistidine establishes that this enzyme is characterized by relatively broad substrate specificity, being able to oxidize positively charged and large hydrophobic d-amino acids bound within a flask-like cavity.


[Penile hemodynamics in health and vasculogenic erectile dysfunction].
Basal circulation, oscillations in microcirculation and microvascular tonicity were studied in patients with and without erectile dysfunction. High informative value of laser flowmetry of the penis was stated in detection of early microcirculatory disorders. The role of these disorders in genesis of vasculogenic erectile dysfunction was determined. The effects of standard conservative therapy in combination with local peloid therapy, quinapril on microcirculation disturbances in the penis were analysed.