Sweat pore reactivity as a surrogate measure of sympathetic nervous system activity in trauma-exposed individuals with and without posttraumatic stress disorder.
Stress analysis by FLIR (forward-looking infrared) evaluation (SAFE) has been demonstrated to monitor sweat pore activation (SPA) as a novel surrogate measure of sympathetic nervous system (SNS) activity in a normal population. SNS responses to a series of 15 1-s, 82 dB, white noise bursts were measured by skin conductance (SC) and SAFE monitoring of SPA on the fingers (FiP) and face (FaP) in 10 participants with posttraumatic stress disorder (PTSD) and 16 trauma-exposed participants without PTSD (Mage = 48.92 ± 12.00 years; 26.9% female). Within participants, SC and FiP responses across trials were strongly correlated (r = .92, p < .001). Correlations between SC and FaP (r = .76, p = .001) and between FiP and FaP (r = .47, p = .005) were smaller. The habituation of SNS responses across the 15 trials was substantial (SC: d = -2.97; FiP: d = -2.34; FaP: d = -1.02). There was a strong correlation between habituation effects for SC and FiP (r = .76, p < .001), but not for SC and FaP (r = .15, p = .45) or FiP and FaP (r = .29, p = .16). Participants with PTSD showed larger SNS responses to the first loud noise than those without PTSD. PTSD reexperiencing symptoms assessed by the PTSD Checklist on the day of testing were associated with the SNS responses to the first loud noise measured by SC (d = 1.19) and FiP (d = .99), but not FaP (d = .10). This study confirms convergence of SAFE and SC as valid measures of SNS activity. SAFE FiP and SC responses were highly predictive of self-rated PTSD reexperiencing symptoms. SAFE may offer an attractive alternative for applications in PTSD and similar populations.


Saffron carotenoids (crocin and crocetin) binding to human serum albumin as investigated by different spectroscopic methods and molecular docking.
Therapeutic effects of saffron ingredients were studied in some diseases. The pharmacokinetics and pharmacodynamics of these ingredients were also studied, but their transport mechanism is not clearly known. Serum albumin has been known as the most important transporter of many drugs in the body that affects their disposition, transportation, and bioavailability. Here, we investigated the interaction of crocin (Cro) with HSA, for the first time, and compared with the crocetin (Crt)-HSA interaction. UV and fluorescence spectroscopy, circular dichroism (CD), and molecular docking was applied to investigate the possibility and mechanism of binding of HSA with these natural carotenoids. The gradually addition of Cro increased HSA absorbency at 278 nm, while Crt decreased it. Both of these changes induced HSA unfolding that was confirmed by the decreased α-helix content, as determined by the CD. Both carotenoids quenched HSA fluorescence emission, but with different mechanisms. The Stern-Volmer plots indicated a dynamic quenching of intrinsic emission of HSA due to Cro addition, while Crt quenching followed both static and dynamic quenching mechanisms. Docking results indicated binding of Cro/Crt in sub-domain IIA, Sudlow site I of HSA, which accompanied with the hydrogen bonding of Cro/Crt with Tyr138. The interaction of these ligands (Cro/Crt) caused HSA unfolding and affects the hydrophobic environment of Trp241, which result in the quenching of Trp fluorescence. The UV spectroscopy and fluorescence quenching data indicated the differences in the mechanisms of interaction of Cro/Crt with HSA, which is due to the differences in the structure and hydrophobicity of these ligands.


Using a cotton thread-based colorimetric sensor modified by carboxymethylcellulose and cuprizone with smartphone detection for quantification of copper.
In the present work, we report the development of a novel cotton thread-based colorimetric sensor modified by carboxymethylcellulose (CMC) and cuprizone (CPZ) with smartphone detection and its application for the quantitative determination of cupric ions in water and cachaça. The cotton thread/smartphone detection-based colorimetric method is an easily affordable, low-cost technique which allows one to perform real-time and on-field determination analyses, especially with limited financial resources. The method involves the complexation of Cu(II) with CPZ, which causes a change in the coloration of the cotton thread from a shade of white to blue in the detection zone of the colorimetric sensor. The immobilization of CPZ on CMC in the cotton thread leads to the pre-concentration of Cu(II) via a complexation mechanism with colorimetric reaction. The application of the colorimetric sensor allows the quantification of copper in the range from 1 to 12 mg L-1, with a low limit of detection of 0.21 mg L-1. In addition, the recovery assays conducted in samples of water and cachaça resulted in recovery percentages ranging from 84.9% to 107%, which is indicative of a precise method. To validate the precision of the proposed colorimetric method, the values obtained from the quantification analysis were compared with those of the flame atomic absorption spectrometry and a good agreement at the 95% confidence level was obtained.


33S hyperfine interactions in H2S and SO2 and revision of the sulfur nuclear magnetic shielding scale.
Using the Lamb-dip technique, the hyperfine structure in the rotational spectra of H2(33)S and (33)SO2 has been resolved and the corresponding parameters--that is, the sulfur quadrupole-coupling and spin-rotation tensors--were determined. The experimental parameters are in good agreement with results from high-level coupled-cluster calculations, provided that up to quadruple excitations are considered in the cluster operator, sufficiently large basis sets are used, and vibrational corrections are accounted for. The (33)S spin-rotation tensor for H2S has been used to establish a new sulfur nuclear magnetic shielding scale, combining the paramagnetic part of the shielding as obtained from the spin-rotation tensor with a calculated value for the diamagnetic part as well as computed vibrational and temperature corrections. The value of 716(5) ppm obtained in this way for the sulfur shielding of H2S is in good agreement with results from high-accuracy quantum-chemical calculations but leads to a shielding scale that is about 28 ppm lower than the one suggested previously in the literature, based on the (33)S spin-rotation constant of OCS.


Efficacy of Antiarrhythmic Drugs Short-Term Use After Catheter Ablation for Atrial Fibrillation (EAST-AF) trial.
Substantial portion of early arrhythmia recurrence after catheter ablation for atrial fibrillation (AF) is considered to be due to irritability in left atrium (LA) from the ablation procedure. We sought to evaluate whether 90-day use of antiarrhythmic drug (AAD) following AF ablation could reduce the incidence of early arrhythmia recurrence and thereby promote reverse remodelling of LA, leading to improved long-term clinical outcomes. A total of 2038 patients who had undergone radiofrequency catheter ablation for paroxysmal, persistent, or long-lasting AF were randomly assigned to either 90-day use of Vaughan Williams class I or III AAD (1016 patients) or control (1022 patients) group. The primary endpoint was recurrent atrial tachyarrhythmias lasting for >30 s or those requiring repeat ablation, hospital admission, or usage of class I or III AAD at 1 year, following the treatment period of 90 days post ablation. Patients assigned to AAD were associated with significantly higher event-free rate from recurrent atrial tachyarrhythmias when compared with the control group during the treatment period of 90 days [59.0 and 52.1%, respectively; adjusted hazard ratio (HR) 0.84; 95% confidence interval (CI) 0.73-0.96; P = 0.01]. However, there was no significant difference in the 1-year event-free rates from the primary endpoint between the groups (69.5 and 67.8%, respectively; adjusted HR 0.93; 95% CI 0.79-1.09; P = 0.38). Short-term use of AAD for 90 days following AF ablation reduced the incidence of recurrent atrial tachyarrhythmias during the treatment period, but it did not lead to improved clinical outcomes at the later phase.


Generation and characterization of a Müller-glial-cell-specific Il6ra knockout mouse to delineate the effects of IL-6 trans-signaling in the retina.
Interleukin-6 (IL-6) is implicated in various retinal and vascular complications associated with diabetic retinopathy (DR). This cytokine functions through two main modalities: classical signaling, in cells expressing the membrane-bound receptor (IL-6Rα); and trans-signaling, possible in most cells through a soluble form of the receptor (sIL-6R). These pathways are considered to be anti-inflammatory and pro-inflammatory, respectively. Our recent studies in retinal endothelial cells and diabetic mice have shown that inhibiting only IL-6 trans-signaling is sufficient to prevent increased vascular leakage, oxidative stress, and inflammation characteristic of DR. Isolating the specific effects of each signaling pathway, however, remains difficult in cells expressing IL-6Rα that are thus capable of both classical and trans-signaling. Müller glial cells (MGCs), the most abundant retinal macroglial cells, span the entire retinal thickness with vital roles in maintaining retinal homeostasis and regulating the blood-retinal barrier through secreted factors. The specific effects of IL-6 trans-signaling in MGCs remain poorly understood given their responsiveness to both IL-6 signaling modalities. In this study, we addressed these concerns by generating an MGC-specific knockout mouse using Cre-loxP deletion of the Il6ra cytokine-binding region. We assessed transcriptional and translational Il6ra expression to confirm the knockout and characterized the effects of knockout on visual functioning in these mice.


Clinico-Microbiological Investigation of Catheter Associated Urinary Tract Infection by Enterococcus faecalis: vanA Genotype.
Prolonged hospitalization and exposure to third generation cephalosporins are reported to facilitate the acquisition and colonization of Vancomycin Resistant Enterococci (VRE). Though VRE is not uncommon in India, urinary tract infection with a vanA genotype is a cause of serious concern as VRE co-exhibit resistance to aminoglycosides. In India, majority of the VRE isolates recovered from hospitalized patients include Enterococcus faecium. We report a case of catheter associated urinary tract infection by an endogenous, multidrug resistant E. faecalis of vanA genotype following prolonged hospitalization, ICU stay, catheterisation and exposure to 3G cephalosporin and metronidazole. The patient responded to linezolid therapy.


Subclavian artery pseudoaneurysm successful exclusion with a covered self-expanding stent.
Subclavian pseudoaneurysms are rare clinical entities occurring most commonly after iatrogenic injury to the subclavian artery. The management of subclavian pseudoaneurysms remains a challenge because of their non-compressibility and close proximity to vital intra-thoracic structures. Until recently, the treatment of choice was surgical intervention. In this case report, an iatrogenic subclavian pseudoaneurysm was successfully managed using a covered, self-expanding stent after an uncovered stent was unsuccessful in sealing the pseudoaneurysm.


Oxygen-dependent microbicidal systems of phagocytes and host defense against intracellular protozoa.
The role of oxygen-dependent microbicidal systems of leukocytes in the host defense against the major nonerythrocytic intracellular protozoa which infect man--Toxoplasma gondii, Trypanosoma cruzi, and the Leishmania species--is reviewed. The hydrogen peroxide-halide-peroxidase microbicidal system is uniformly cidal to these organisms in vitro. Peroxidase-independent oxygen product(s) toxicity is more variable. Studies to data indicate that phagocytes which contain granule peroxidase and which have the capacity to generate a vigorous respiratory burst; eg, neutrophils and monocytes, possess substantial activity against these protozoa. The absence of granule peroxidase together with the markedly attenuated respiratory burst of resident macrophages leaves these cells with a severe microbicidal defect. These protozoa can enter resident macrophages in the absence of antibody and survive and replicate within the intracellular environment. Enhancement of the antiparasite activity of resident macrophages can be accomplished either by activation of these cells by exposure to sensitized T-cell products, or by the introduction of exogenous peroxidase into the vacuole. Other factors influencing the ability of protozoa to survive intracellularly include the capacity of these organisms to avoid effective triggering of the macrophage respiratory burst and the levels of endogenous scavengers of oxygen products within the parasite.


Optical Coherence Tomography Findings in the Junctional Scotoma of Traquair.
A 43-year-old woman presented with a right-sided visual field defect in the right eye. The visual acuity was normal and there was a right relative afferent pupillary defect. Formal visual field testing revealed a junctional scotoma of Traquair. The fundus examination showed optic atrophy in the right eye and optical coherence tomography demonstrated unilateral band atrophy. Neuroimaging revealed a sellar and suprasellar cystic pituitary adenoma for which she underwent a transsphenoidal drainage. We demonstrate the clinical and radiographic features of the junctional scotoma of Traquair and describe the differentiating features vs the junctional scotoma.


Occurrence and mechanisms of amikacin resistance and its association with beta-lactamases in Pseudomonas aeruginosa: a Korean nationwide study.
We investigated the occurrence and mechanism of amikacin resistance and its association with various beta-lactamase genes in Pseudomonas aeruginosa isolates. Of the total 250 consecutive, non-duplicated isolates of P. aeruginosa, 55 isolates showed amikacin resistance. PCR amplification of genes for aminoglycoside (AG)-modifying enzymes [aac(3)-I, aac(3)-II/VI, aac(3)-III/IV, aac(6')-I, aac(6')-II, ant(2'')-I, ant(4')-II and aph(3')-VI], 16S rRNA methylases (rmtA, rmtB, rmtC and armA) and class 1 integrons was performed. In addition, we analysed the association of AG resistance genes with various beta-lactamase genes. In Korea, the amikacin resistance rate in P. aeruginosa was high (22%), and it varied among provinces (3.8% to 40%). Four types of AG-modifying enzyme genes [aph(3')-VI, ant(2'')-I, aac(6')-I and aac(3)-II/VI] were found in 48 isolates. Thirty-six strains harboured two or more types of enzymes, of which a combination of aph(3')-VI and ant(2'')-I was the most frequent (24/36 isolates, 66.7%). None harboured aac(3)-I, aac(3)-III/IV, aac(6')-II, ant(4')-II, rmtA, rmtB, rmtC or armA. Forty-two isolates co-harboured beta-lactamase genes (mostly bla(OXA-10)). A class 1 integron was detected in all but one, and all the ant(2'')-I and 26/29 bla(OXA-10) were found in it. In contrast, aph(3')-VI was not found to be associated with the class 1 integron. Considering the possibility of co-selection and dissemination, constant monitoring of resistance evolution is necessary.


Ecophysiological tolerance of duckweeds exposed to copper.
Although essential for plants, copper can be toxic when present in supra-optimal concentrations. Metal polluted sites, due to their extreme conditions, can harbour tolerant species and/or ecotypes. In this work we aimed to compare the physiological responses to copper exposure and the uptake capacities of two species of duckweed, Lemna minor (Lm(EC1)) and Spirodela polyrrhiza (SP), from an abandoned uranium mine with an ecotype of L. minor (Lm(EC2)) from a non-contaminated pond. From the lowest Cu concentration exposure (25microM) to the highest (100microM), Lm(EC2) accumulated higher amounts of copper than Lm(EC1) and SP. Dose-response curves showed that Cu content accumulated by Lm(EC2) increases linearly with Cu treatment concentrations (r(2)=0.998) whereas quadratic models were more suitable for Lm(EC1) and SP (r(2)=0.999 and r(2)=0.998 for Lm(EC1) and SP, respectively). A significant concentration-dependent decline of chlorophyll a (chl a) and carotenoid occurred as a consequence of Cu exposure. These declines were significant for Lm(EC2) exposed to the lowest Cu concentration (25microM) whereas for Lm(EC1) and SP a significant decrease in chl a and carotenoids was observed only at 50 and 100microM-Cu. Electric conductivity (EC) and malondialdehyde (MDA) content increased after Cu exposure, indicating oxidative stress. Significant increase of EC was observed in Lm(EC2) for all Cu concentrations whereas the increase for Lm(EC1) and SP became significant only after an exposure to 50microM-Cu. On the contrary, for Lm(EC1), SP, and Lm(EC2), MDA content significantly increased even at the lowest concentration. Protein content and catalase (CAT) activity showed a decrease with an increase in Cu concentration. For the species Lm(EC1) and SP, a significant effect of copper on CAT activity was observed only at the highest concentration (100microM-Cu) whereas, for Lm(EC2), this effect started to be significant after an exposure to 50microM-Cu. Superoxide dismutase (SOD) activity increased with increasing concentrations of Cu, with a very similar trend between the three populations of duckweed. However, due to the facts that enzyme activity is expressed as units of activity per gram of protein and that protein content decreased with Cu exposure, the increase in SOD activity might partly result from a relative increase of this enzyme inside the pool of proteins. Consequently, the results obtained in our experimental conditions strongly suggest that duckweed species from the uranium-polluted area have developed mechanisms to cope with metal toxicity and that this tolerance is based on the existence of protective mechanism to limit the metal uptake rather than on an enhancement of the antioxidative metabolism.


Dibutyl phthalate-induced oxidative stress and apoptosis in swine testis cells and therapy of naringenin via PTEN/PI3K/AKT signaling pathway.
Dibutyl phthalate (DBP) is a phthalic acid ester (PAE) that has posed a health hazard to the organisms. Naringenin (NRG) is a flavanone compound that has shown protection against several environmental chemicals through suppression of oxidative stress and activation of phosphatidylinositol 3-kinase/threonine kinase (PI3K/AKT) signaling pathway. Herein, swine testis (ST) cells were treated with 1.8 μM of DBP or/and 25.39 nM of NRG for 24 h, we described the discovery path of NRG inhibition on apoptosis in DBP-exposed ST cells through targeting phosphatase and tensin homologue deleted on chromosome 10 (PTEN). We first found that the anti-apoptosis effect of NRG is dependent on mitochondrial pathway through flow cytometry and related gene/protein expression, and then we detected PI3K/AKT pathway-related gene/protein expression, and established a computational docking assay between NRG and PTEN. We found that NRG specifically binds to three basic residues (His93, Lys125, Lys128) of P loop in PTEN, as well as phosphatase domains (Asp92, His93, Cys124, Lys125, Ala126, Lys128, and Arg130) in active dephosphorylation pockets, thereby reducing PTEN level and activating PI3K/AKT signaling pathway, and further inhibiting oxidative stress and mitochondrial pathway apoptosis. Taken together, our results push forward that NRG deserves further attention as a potential antagonistic therapy against DBP through targeting PTEN to inhibit oxidative stress and activate PI3K/AKT signaling pathway.


Dementia at the End of Life and Family Partners: A Symbolic Interactionist Perspective on Communication.
People with dementia are not dying; they are experiencing changes in the brain. This paper utilizes a symbolic interaction theoretical perspective to outline communicative alternatives to polypharmacy. There is a growing interest in sociological interventions to untangle the "disordered discourses" associated with dementia. Such practices challenge common stigmas attached to dementia as an "ongoing funeral" or "death certificate." Changing the expectations, attitudes and communication patterns of family care partners can positively impact them and the person living with dementia at the end of life. This paper delineates multiple non-verbal communication interventions (e.g., the trip back in time, dementia citizenship and sensory engagement modalities) to explore techniques to engage persons with advanced dementia.


Analysis of mRNA recognition by human thymidylate synthase.
Expression of hTS (human thymidylate synthase), a key enzyme in thymidine biosynthesis, is regulated on the translational level through a feedback mechanism that is rarely found in eukaryotes. At low substrate concentrations, the ligand-free enzyme binds to its own mRNA and stabilizes a hairpin structure that sequesters the start codon. When in complex with dUMP (2'-deoxyuridine-5'-monophosphate) and a THF (tetrahydrofolate) cofactor, the enzyme adopts a conformation that is unable to bind and repress expression of mRNA. Here, we have used a combination of X-ray crystallography, RNA mutagenesis and site-specific cross-linking studies to investigate the molecular recognition of TS mRNA by the hTS enzyme. The interacting mRNA region was narrowed to the start codon and immediately flanking sequences. In the hTS enzyme, a helix-loop-helix domain on the protein surface was identified as the putative RNA-binding site.


Thermodynamics of mixed surfactant solutions of N,N'-bis(dimethyldodecyl)-1,2-ethanediammoniumdibromide with 1-dodecyl-3-methylimidazolium bromide.
Mixed surfactant solutions are studied to understand their synergistic effects. Here we report the micellization properties of mixed surfactant solutions of the gemini surfactant N,N'-bis(dimethyldodecyl)-1,2-ethanediammoniumdibromide (12-2-12) with the imidazolium ionic liquid 1-dodecyl-3-methylimidazolium bromide (C12mimBr) investigated by isothermal titration calorimetry (ITC), conductometry, fluorimetry, and dynamic light scattering (DLS). A two-parameter Margules model was successfully used to correlate the cmc values and calculate the compositions and activity coefficients of the two components in the mixed micelle phase for 12-2-12/C12mimBr aqueous solutions with different overall surfactant compositions. The dissociation degree of counterion, the thermodynamic quantities of micellization, and the excess thermodynamic quantities for the mixed micelle were calculated and discussed. The ITC experiment in the low overall surfactant composition region showed a second phase transition. A thermodynamic model was proposed to explore phase behaviors of two different types of micelle and their solution, which was further confirmed by fluorescence and DLS studies.


Interfacing quantum-optical and solid-state qubits.
We present a generic model of coupling quantum-optical and solid-state qubits, and the corresponding transfer protocols. The example discussed is a trapped ion coupled to a charge qubit (e.g., Cooper pair box). To enhance the coupling and to achieve compatibility between the different experimental setups we introduce a superconducting cavity as the connecting element.


Characterization of the autoantigen La as a nucleic acid-dependent ATPase/dATPase with melting properties.
The autoantigen La, a known transcription termination factor of RNA polymerase III, was purified to homogeneity from mouse 3T3 cells and calf thymus by different isolation procedures. The La protein from calf thymus was separated into RNA binding and nonbinding subclasses. The murine La protein and the RNA binding subclass of calf thymus La protein showed ATPase/dATPase activity in the presence of DNA-RNA or RNA-RNA hybrids. A novel monoclonal anti-La antibody (La11G7) and patients' anti-La antibodies immunoadsorbed to homogeneously purified La protein were able to inhibit the enzyme activity of La protein. La protein was able to melt a synthetic DNA-RNA hybrid in a reaction that required ATP hydrolysis. The RNA binding ability of the nonbinding subclass was restored by treatment with sialidase. This treatment also restored the protein's ATP-dependent melting activity.


Inhibitory effect of allyl and benzyl isothiocyanates on ochratoxin a producing fungi in grape and maize.
The purpose of this study was to evaluate the inhibitory effect of allyl-isothiocyanate (AITC) and benzyl-isothiocyanate (BITC) on fungal growth and Ochratoxin A (OTA) production by Aspergillus ochraceus, A. carbonarius and A. niger. Here, we found that spore germination and fungal growth of the three fungi were significantly inhibited when the concentration of AITC and BITC was higher than 1.25 μg/mL. The inhibitory effect of AITC or BITC on A. carbonaceus and A. ochraceus was significantly stronger than that of A. niger. Scanning electron microscopy showed that the mycelia of all three fungi were changed by AITC and BITC. Compared with A. ochraceus and A. carbonarius, the damage to A. niger was lower. For OTA production, AITC and BITC could significantly down-regulated the expression of all five OTA biosynthesis genes in A. niger and A. carbonarius. In A. ochraceus, although several OTA biosynthesis genes were up-regulated, the key PKS gene was down-regulated by AITC and BITC. Twenty-five μg/mL of AITC or BITC could reduce the infection of the three fungi on grapes with inhibition rates of 28%-36% during 14 days and prolong the shelf life of grapes. In maize, the OTA production of the three fungi was significantly reduced by 25 μg/mL of AITC and BITC with the inhibition rates 68.04%-93.49% and 65.87%-75.45%, respectively. These results suggest that AITC and BITC can be used as natural fungicides to prevent A. niger, A. carbonarius and A. ochraceus from infecting grapes and maize and control OTA contamination.


Client-server multitask learning from distributed datasets.
A client-server architecture to simultaneously solve multiple learning tasks from distributed datasets is described. In such architecture, each client corresponds to an individual learning task and the associated dataset of examples. The goal of the architecture is to perform information fusion from multiple datasets while preserving privacy of individual data. The role of the server is to collect data in real time from the clients and codify the information in a common database. Such information can be used by all the clients to solve their individual learning task, so that each client can exploit the information content of all the datasets without actually having access to private data of others. The proposed algorithmic framework, based on regularization and kernel methods, uses a suitable class of "mixed effect" kernels. The methodology is illustrated through a simulated recommendation system, as well as an experiment involving pharmacological data coming from a multicentric clinical trial.


[Digital subtraction radiology in the study of mobile structures of the larynx].
Digital subtraction radiography (DSR) was applied to the study of the larynx in 11 healthy subjects and 15 pathological cases. The method, consisting in the subtraction of images obtained at rest and during phonation or respiratory phases, allowed a clear definition of the normal moving structures--i.e. vocal cords, false cords, pyriform sinuses, thyroid cartilage. Moreover, several pathological conditions could be demonstrated. DSR asserts thus itself as a suitable technique in the functional evaluation of the glottis.


Elements behind sedentary lifestyles and unhealthy eating habits in individuals with severe obesity.
This study examines elements behind sedentary lifestyles and unhealthy eating habits in individuals who lived with severe obesity during many years of their lives. Ten post-bariatric surgery patients participated in semi-structured interviews 7 months after surgery. A year later, a second round of interviews was also conducted to address some knowledge gaps related to the study purpose. The qualitative data collected were analysed through content analysis. Embarrassment about showing their body publicly, pain and poor physical condition, and bad experiences in non-inclusive physical activity contexts were found as potential elements that contributed to their adherence to sedentary lifestyles. Poor family food education, loss of a loved one, family problems, arguments or disputes, and past traumatic events (e.g., childhood sexual abuses) could be related to their development of unhealthy eating behaviours. Findings also pointed out that participants' failed attempts to lose weight provoked them anxiety, feelings of failure and rebellion, and influenced their return to an unhealthy diet and a sedentary lifestyle. This study may be helpful to reveal some elements which could be related to the origin and perpetuation of severe obesity, and to design prevention/treatment strategies from a more holistic, sensitive, and respectful perspective.


Effects of ronnel on growth, endocrine function and blood measurements in steers and rats.
Four feeding trials were conducted to determine (1) how the organophosphate ronnel affects thyroid and adrenal circulating hormone levels and blood profile measurements of beef steers and (2) whether the effects of ronnel observed in beef steers could be produced in growing rats. In trial 1, four groups of eight steers each were given either no ronnel or 4 mg ronnel/kg body weight daily in diets fed at either limited (1.8% of body weight) or ad libitum intake. After 7 weeks, intake levels, but not ronnel treatments, were reversed during a 1-week transition period, and feeding was continued for another 7 weeks. In trial 2, four groups of six steers each were given 0, 44, 88 or 176 ppm ronnel premixed in diets fed ad libitum for 18 weeks. Actual ronnel intakes averaged 0, 1.01, 2.12 and 4.73 mg/kg body weight daily in trial 2. In trials 3 and 4 , growth and intake were measured in 64 and 32 growing Sprague-Dawley rats, respectively, fed levels of ronnel ranging from 0 to 100 ppm in the diet. In trial 3, blood plasma was analyzed at various times for triiodothyronine (T3), thyroxine (T4), cholesterol and total lipid content. In trial 1, the concentration of Plasma T4 was 1.31 times higher in steers fed ronnel that in control steers. In trial 2, plasma T4 was 1.30 times higher in steers fed 176 ppm ronnel, the level that improved growth, than in steers fed the lower ronnel levels. Circulating levels of T3, cortisol and aldosterone were similar for both control and ronnel-fed steers. Serum cholesterol concentrations were consistently higher in ronnel-fed steers. The data indicated that the growth-promoting effect of ronnel in steers may be associated with a shift in thyroid function. Effects of ronnel in steers were not observed in rats, demonstrating a species difference between steers and rats.


Identification of potential drugs for Parkinson's disease based on a sub-pathway method.
Parkinson's disease (PD) is the second most prevalent neurodegenerative disease in ageing individuals. Current therapeutic regimen suffers from general side effects and a poor efficiency for PD symptoms. The need for development new therapeutic agents for PD is urgent. Here, we aimed to explore the metabolic mechanism of PD and identified potential novel agents for PD by a sub-pathway-based method. By using the GSE7621 microarray data from the GEO database, we first identified the 1226 differentially expressed genes (DEGs) between PD and normal samples. Then we identified 19 significant enriched metabolic sub-pathways, which may involve in development of PD. Finally, by an integrated analysis of PD-involved sub-pathways and drug-affected sub-pathways, we identified 49 novel small molecular drugs capable to target the PD-involved sub-pathways. Our method could not only identify existing drug (apomorphine) for PD, but also predict potentially novel agents (ketoconazole and astemizole), which might have therapeutic effects via targeting some key enzymes in arachidonic acid metabolism. These candidate agents identified by our approach may provide insights into a novel therapy approach for PD.


Adsorption modes of cysteine on Au(111): thiolate, amino-thiolate, disulfide.
The adsorption of cysteine on the (111) surface of gold has been studied by means of periodic supercell density-functional theory calculations. A number of different adsorption modes are examined, including adsorption through the thiol group in either thiolate or disulfide form, and adsorption through both the thiol and amino functional groups. We find that at intermediate coverage densities the latter mode of adsorption is favored, followed by thiolate adsorption at the bridge (slightly displace toward fcc) site. The N-Au and S-Au bond strengths in the amino-thiolate adsorption are estimated to be of the order of 6 and 47 kcal/mol, respectively. The electronic structure of the different systems is analyzed, with focus on the total and projected density of states, as well as on the detailed character of the electronic states at the interface. States near the Fermi energy are found to have a metal-molecule antibonding character, whereas metal-molecule bonding states mostly occur near the lower edge of the Au-d band.


Magnetic resonance and functional magnetic resonance imaging: tools for the study of human epilepsy.
The development of new magnetic resonance imaging base neuroimaging techniques is increasing the utility and the importance of magnetic resonance imaging in the investigation of patients with epilepsy. Recent advances in magnetic resonance imaging, magnetic resonance spectroscopy and functional magnetic resonance imaging are not only providing relevant clinical information regarding human epilepsy but are also revealing important insights into its basic mechanisms. In the present review the role of these new technologies is discussed in the context of their clinical utility.


Ultrasound Shear-Wave Elastography for Follow-Up Fat Induration after Breast Reconstruction with an Autologous Flap.
Fat induration is associated with necrosis and remains a common complication in breast reconstructions with autologous flaps after mastectomy. Fat induration can cause deep tissue infection, pain, distress, and anxiety. However, the diagnosis for this problem has not been objectively defined. In the current article, We will share our experience of using ultrasound shear-wave elastography with 14 patients who had clinical fat induration after breast reconstruction with a deep inferior epigastric perforator (DIEP) flap. The experience suggested that shear wave elastography may be a noninvasive tool to assess alterations of tissue stiffness in a reproducible fashion after breast reconstruction with DIEP flaps. Complications, such as fat necrosis and fatty induration, may occur as a result of unstable blood flow to the flap. Thereby, objective assessments of stiffness might make a major contribution to the understanding of hemodynamics of the DIEP flap after transplantation.


Monitoring pesticide residues in dates marketed in Al-Qassim, Saudi Arabia using a QuEChERS methodology and liquid chromatography-tandem mass spectrometry.
A sensitive, simple and rapid QuEChERS extraction method and liquid chromatography equipped with triple quadrupole mass spectrometry (LC-MS/MS) were used to determine 42 pesticides in dates. Acidified acetonitrile and citrate buffer salts were used to extract re-hydrated samples. Acceptable validation performances were achieved, i.e. recovery range of 70-120% and RSD values ≤20% for 42 analytes at three different concentrations:100, 50 and 10 μg/kg. This method was used to analyse 200 date fruit samples (var. Sukkari) collected from different large markets in the Al-Qassim region in Saudi Arabia. Pesticide residues were detected in 36 (18%) of the date fruits samples, and 15 samples (7.5%) exceeded the maximum residue levels. The ruggedness test results showed that this method is robust and suitable for the determination of pesticide residues in dates. Additionally, the results showed that the monitored dates did not have a health impact on consumers in Saudi Arabia during the study period.


Evolution, diversification and function of the maternal-infant dyad in mammalian feeding.
The evolution of the mother/infant dyad providing a source of nutrition for infants is essential for the origin and subsequent diversification of mammals. Despite the importance of this dyad, research on maternal and infant function is often treated independently. Our goal is to synthesize the work on maternal and infant function, discuss our own studies of suckling, and compare the origins of lactation and suckling with their ensuing diversification. Our central premise is that while extensive work has demonstrated variation across mammals in the maternal aspect of this system, very little has been done to address how this relates to infant function. We start with a discussion of the fundamental anatomy and physiology of both mother and infant. We next discuss the origin of mammary glands and milk, and infant suckling, which is distinct from their subsequent diversification. We then discuss the diversification of maternal and infant function, highlighting the evolutionary diversity present in maternal function (both anatomically and physiologically), before arguing that the diversity of infant function is unexplored, and needs to be better studied in the future. We end by discussing some of the holes in our understanding, and suggestions for future work that can address these lacunae. This article is part of the theme issue 'Food processing and nutritional assimilation in animals'.


Linking rates of diffusion and consumption in relation to resources.
The functional response is a fundamental model of the relationship between consumer intake rate and resource abundance. The random walk is a fundamental model of animal movement and is well approximated by simple diffusion. Both models are central to our understanding of numerous ecological processes but are rarely linked in ecological theory. To derive a synthetic model, we draw on the common logical premise underlying these models and show how the diffusion and consumption rates of consumers depend on elementary attributes of naturally occurring consumer-resource interactions: the abundance, spatial aggregation, and traveling speed of resources as well as consumer handling time and directional persistence. We show that resource aggregation may lead to increased consumer diffusion and, in the case of mobile resources, reduced consumption rate. Resource-dependent movement patterns have traditionally been attributed to area-restricted search, reflecting adaptive decision making by the consumer. Our synthesis provides a simple alternative hypothesis that such patterns could also arise as a by-product of statistical movement mechanics.


Knowledge of different medical and dental professional groups in Switzerland about halitosis.
Although halitosis is a widespread condition, it is still seen as too personal or embarrassing to talk about. The cause of real halitosis can be intraoral or extraoral. In order to determine the level of knowledge of health care providers in Switzerland, a survey was conducted over a period of three years in which 150 family physicians, 150 ear, nose and throat specialists, 154 dentists and 151 dental hygienists were personally interviewed. The survey shows that only 46.7% of the dentists and only 47.0% of the dental hygienists are consulted by patients for their halitosis, whereas 58.0% of the family physicians and 50.7% of the ENT specialists reported treating 1-10 patients for halitosis per year, while 46.7% of the ENT doctors even reported treating 11-100 patients for halitosis per year. 81.5% of all interviewed doctors and dental hygienists were of the opinion that halitosis mainly originates intraorally. 76.0% of the dentists and 72.8% of the dental hygienists as well as 33.3% of the family physicians recommend periodontitis therapy as halitosis treatment. This proves that a large percentage of medical professionals thinks that marginal periodontitis is the most common cause of halitosis. This study also shows that patients seek first consultations with dentists and dental hygienists less often than with family physicians and ENT specialists, despite the fact that the cause of halitosis is primarily intraoral.


Effects of Two Different Dietary Patterns on Inflammatory Markers, Advanced Glycation End Products and Lipids in Subjects without Type 2 Diabetes: A Randomised Crossover Study.
Epidemiological studies suggest that consumption of red and processed meat and refined grains are associated with type 2 diabetes and metabolic syndrome and increased inflammatory and fibrinolytic markers. We hypothesised that a diet high in red and processed meat and refined grains (HMD) would increase inflammatory markers and advanced glycation end products (AGEs) compared with a diet high in dairy, whole grains, nuts and legumes (HWD). We performed a randomised crossover study of two four-week interventions in 51 participants without type 2 diabetes (15 men and 36 women aged 35.1 ± 15.6 years; body mass index: 27.7 ± 6.9 kg/m²). No baseline measurements were performed. Plasma fluorescent AGEs, carboxymethyllysine, glucose, insulin, lipids, hs-CRP, interleukin 6 (IL-6) and plasminogen activator inhibitor-1 (PAI-1) were analysed after four weeks on each diet. IL-6, hs-CRP, AGEs and carboxymethyllysine were not different between diets but PAI-1 was higher after the HMD than after HWD ((median and interquartile range) 158, 81 vs. 121, 53 ng/mL p < 0.001). PAI-1 on the HWD diet was inversely correlated with whole grains intake (p = 0.007). PAI-1 was inversely correlated with insulin sensitivity index (r = -0.45; p = 0.001) and positively correlated with serum total cholesterol (r = 0.35; p = 0.012) and serum triglyceride (r = 0.32; p = 0.021) on HMD. This trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12614000519651).


Regulated binding of the protein kinase C substrate GAP-43 to the V0/C2 region of protein kinase C-delta.
The interaction between protein kinase C-delta and its neuronal substrate, GAP-43, was studied. Two forms of protein kinase C-delta were isolated from COS cells and characterized by differences in gel mobility, GAP-43 binding, and specific GAP-43 and histone kinase activities. A slow migrating, low specific activity form of protein kinase C-delta bound directly to immobilized GAP-43. Binding was abolished in the presence of EGTA, suggesting Ca2+ dependence of the interaction. The free catalytic domain of protein kinase C-delta did not bind GAP-43, suggesting the existence of a binding site in the regulatory domain. Glutathione S-transferase-protein kinase C-delta regulatory domain fusion proteins were generated and tested for binding to GAP-43. The V0/C2-like amino-terminal domain was defined as the GAP-43-binding site. GAP-43 binding to this region is inhibited by EGTA and regulated at Ca2+ levels between 10(-7) and 10(-6) M. The interaction between protein kinase C-delta and GAP-43 was studied in intact cells by coexpression of the two proteins in human embryonic kidney cells followed by immunoprecipitation. Complex formation occurred only after treatment of the cells with the Ca2+ ionophore ionomycin, indicating that elevation of intracellular Ca2+ is required for interaction in vivo. It is concluded that protein kinase C-delta interacts with GAP-43 through the V0/C2-like domain, outside the catalytic site, and that this interaction is modulated by intracellular Ca2+.


Diagnosis of acute renal allograft rejection: evaluation of the Banff 97 Guidelines for Slide Preparation.
Arteritis and tubulitis, the diagnostic features of acute renal allograft rejection, are typically focal lesions. To avoid under-diagnosis, the Banff '97 schema recommends the preparation of multiple slides, of which three should be stained with hematoxylin and eosin (H&E) and three with periodic acid-Schiff (PAS) or silver. In this study, we examine the validity of the Banff '97 recommendations and determine how widely these recommendations are applied. We reviewed 52 consecutive renal transplant biopsy specimens showing both acute tubulointerstitial and vascular rejection. Arteritis was graded for each H&E slide, and tubulitis was graded for each H&E and PAS/silver. The handling of renal allograft biopsy specimens in the U.K. was determined by means of a questionnaire. When two, as opposed to three, H&E slides were examined, arteritis was missed in 11.4% of cases; when only one H&E slide was examined, arteritis was missed in 33.3% of cases. When only one, as opposed to three, PAS/silver slide was examined, tubulitis was under-graded in 33.3% of cases. In the U.K., 40% of laboratories stain at least three slides with H&E, and 42% stain at least three slides with PAS/silver. Only 30% of laboratories conform to all the Banff guidelines for slide preparation. There is likely to be significant under-diagnosis and under-grading of acute rejection if the Banff '97 guidelines for slide preparation are not implemented. Most laboratories in the U.K. do not conform to these guidelines.


Release of granulocyte elastase and complement changes during hysterectomy.
Complement activation and release of granulocyte elastase has been previously reported during major vascular surgery and has been ascribed to plasma/cell interactions with foreign surfaces or to administration of blood or plasma. The effect of uncomplicated general anaesthesia and surgery, not requiring blood or plasma, on complement activation and signs of proteinase release was assessed by measuring C3d and elastase-alpha-1 PI, respectively, in nine patients undergoing elective hysterectomy. There was a minor decrease in plasma C3d during anaesthesia, surgery and in the post-operative period caused by the diluting effect of intravenous fluids. Elastase alpha-1 PI remained largely unchanged until the first post-operative day, when a significant increase was seen (p less than 0.05); on the second and third day significant elevated values were still observed. Release of granulocyte elastase seems to be a generalized response to surgical trauma and may be a part of the endocrine-metabolic stress response.


The bud scar-based screening system for hunting human genes extending life span.
We developed a high-throughput screening system that allows identification of genes prolonging life span in the budding yeast Saccharomyces cerevisiae. The method is based on isolating yeast mother cells with an extended number of cell divisions as indicated by the increased number of bud scars on their surface. Fluorescently labeled wheat germ agglutinin (WGA) was used for specific staining of bud scars. Screening of a human HepG2 cDNA expression library in yeast resulted in the isolation of several yeast transformants with a potentially prolonged life span. The budding yeast S. cerevisiae, one of the favorite models used to study aging, has been studied extensively for the better understanding of the mechanisms of human aging. Because human disease genes often have yeast counterparts, they can be studied efficiently in this organism. One interesting example is the WRN gene, the human DNA helicase, which participates in the DNA repair pathway. The mutation of the WRN gene causes Werner syndrome showing premature-aging phenotype. Budding yeast contains WRN homologue, SGS1, and its mutation results in shortening yeast life span. The knowledge gained from the studies of budding yeast will benefit studies in humans for better understanding of aging and aging-related disease.


Predicting the performance of handheld near-infrared photonic sensors from a master benchtop device.
Many industries see a shifting focus towards performing on-site analysis using handheld spectroscopic devices. A determining factor for decision-making on the commissioning of these devices is available information on the potential performance of the device for specific applications. By now, myriad handheld solutions with very different specifications and pricing are available on the market. Although specifications are generally available for new devices, this does not directly quantify or predict how available devices will perform for targeted cases. We present a novel chemometric method to estimate the prediction performance of handheld NIR hardware and apply it to estimate the performance of two commercially available handheld NIR technologies in predicting protein content (ranging 120-180 g kg-1) in pig feed from existing data of a benchtop device. Adjusting benchtop data to the wavelength range and resolution of the handheld device lead to over-optimistic estimates of the handheld performances. Our method additionally utilizes information on the error structure of the handheld devices for the estimation. It yielded performance estimates differing less than 1 g kg-1 from the experimentally determined handheld performances and similar model parameters. Our method was effective for linear and nonlinear calibration algorithms, also when estimating performance after averaging multiple scans. Replicate spectra of twenty samples recorded using the handheld were required for replication error estimation to obtain an accurate performance estimation. The error structure could be reported by manufacturers in the future for this approach to be universally employed for predictive quantitative technology assessment. Overall, our method provides estimates of the performance of a handheld device for a specific task with minimal testing required and can thus be used as a device or application screening tool before committing to develop calibrations.


Enzyme inhibition as a key target for the development of novel metal-based anti-cancer therapeutics.
Historically, DNA has been the target for many metal-based anti-cancer drugs, but drawbacks of prevailing therapies have stimulated the search for new molecular targets which may present unique opportunities for therapeutic exploitation. Enzyme inhibition has recently been identified as an alternative and significant target. The pursuit of novel metallodrug candidates that selectively target enzymes is now the subject of intense investigation in medicinal bioinorganic chemistry and chemical biology. In the field of drug design, it is recognised by many that exploiting the structural and chemical diversity of metal ions for the identification of potential hit and lead candidates can dramatically increase the number of possible drug candidates that may be added to the already abundant armoury of chemotherapeutic agents. This review will focus on recent key advancements in enzyme inhibition as a key target for the development of novel metal-based anti-cancer therapeutics. The enormous clinical success of classical platinum drugs, amongst others, coupled with the wealth of knowledge accumulated in recent years on enzyme structure and function, has undoubtedly been the impetus behind the development of new metallodrug candidates with enzyme inhibitory properties. Recent trends in this field will be reviewed with a particular emphasis on metal complexes that inhibit protein and lipid kinases, matrix metalloproteases, telomerases, topoisomerases, glutathione-S-transferases, and histone deacetylases.


A follow-up cytogenetic study of workers highly exposed inside the Chernobyl sarcophagus.
Data are presented on some of the engineers and scientists who regularly entered highly radioactive areas of the sarcophagus chamber constructed around the ruins of the Chernobyl reactor. Previous investigations on six of them by unstable chromosomal aberrations, quartz fibre electrometers and, in some cases, tooth electron spin resonance have all indicated high doses accumulated over several years of work inside the sarcophagus. Here, the authors present the data on eleven of the men who agreed to be monitored cytogenetically although two have since died aged 45 and 66 y. The present data were combined with the previous to examine the time-courses of these individuals' changes in their aberration frequencies. As expected, dicentric aberrations showed a clear drop down to 2-3 per 100 cells since the men ceased working inside the sarcophagus. In contrast, the translocation yields remained at a high level showing no tendency to decrease and so proved reliable for retrospective biodosimetry. These data are particularly useful in demonstrating the value of FISH long after high but protracted and fractionated exposure.


Balancing flexibility for the employer and the employee: a case study of the development of annualized hours employment contracts.
As with many forms of flexible working, Annualized Hours (AH) systems offer potential benefits to both the employer and the employee. However, the flexibility requirements of employers and employees often conflict. Therefore, when a large food manufacturing organization decided to redesign its AH system, it employed an independent consultancy to act as neutral third party. The consultancy provided technical expertise and assistance in developing an AH system that optimised productivity and was acceptable to the workforce. Data are presented, obtained from focus groups conducted throughout the organization, describing some of the potential difficulties of implementing an AH system. Drawing upon these data, a number of new AH systems were proposed and modelled using specialist software tools. The design process is described, together with the advantages and difficulties associated with use of the software tools. It is concluded that the key elements in the process of designing AH systems are centred around issues of trust and communication; the involvement of a broad range of interested parties, through a process of carefully managed group facilitation; and the need for adequate technical support in the development and evaluation of AH systems.


Stent implantation for acute left main coronary artery occlusion in an HIV-infected patient on protease inhibitors.
A previously unreported complication, acute left main coronary artery occlusion with anterior myocardial infarction, in a patient at low coronary risk under HIV protease inhibitors, is described. Severe premature coronary artery disease has been reported in young men receiving HIV protease inhibitors, usually associated with hypertriglyceridemia, hypercholesterolemia, glucose intolerance and lipodystrophy syndrome. Percutaneous transluminal coronary angioplasty and stent implantation were successfully performed.


Seroepidemiological studies on the occurrence of common respiratory infections in paediatric student nurses and medical technology students.
The occupational risk of acquiring minor respiratory infections for paediatric student nurses was estimated by performing serological examinations with influenza A, B, C, parainfluenza, mumps, respiratory syncytial virus, adenovirus and Mycoplasma pneumoniae at 6-month intervals over a period of 4 years in paediatric student nurses at two schools of nursing and students at one school of medical technology. Titre increases against all tested agents occurred 1.86 times more often in the student nurses than in the medical technology students, the most frequent agents in both groups being influenza A and B. No difference in the relative distribution of the agents could be verified in the two occupational groups. Data on the protective value of pre-infectious antibody levels for influenza A, B, and coronavirus OC43 and on the importance of the spread of single agents among classmates are presented.


Thermal decomposition of carbon precursors in decorated AFI zeolite crystals.
Mass spectrometry and thermogravimetric analysis are used to explore the thermal decomposition of carbon precursors (primarily the tripropylammonium cations) occluded within AlPO(4)-5 (AFI) crystals prepared in various media (in the presence or absence of F(-) ions, Si(4+) substations of P(5+)), with the aim to fabricate high-density 0.4-nm single-walled carbon nanotubes (SWNTs). It has been found that the tripropylammonium precursors exist in the as-synthesized crystals in three different forms: tripropylammonium fluoride, hydroxide, and tripropylammonium cation compensating for the negative charge of the framework. The latter is bonded to the framework by strong chemical interaction and its decomposition takes place by a series of beta-elimination reactions to give propylene and ammonia, with the stepwise formation of dipropylammonium and n-propylammonium cations. The 0.4-nm SWNTs filling density was found to be higher than that resulting from the carbon precursor of tripropylammonium fluoride and hydroxide, because of the strong adsorption force of the channel walls to pyrolysate, as evidenced by the clear and strong radial breathing modes in Raman spectra.


The effect of X irradiation on the progression of mouse 10T1/2 cells released from density-inhibited cultures.
When mouse C3H 10T1/2 cells were allowed to reach the density-inhibited plateau phase of growth, 0-3% of the cells were in the S phase as determined by pulse-labeling indices and about 90% of cells were in the G1 phase as determined by flow microfluorometry (FMF). Density-inhibited cultures were exposed to moderate doses of X ray: immediately after X irradiation the cultures were trypsinized and the cells were subcultured at low density in fresh medium. FMF profiles and pulse and continuous-labeling indices were studied. It was determined by pulse-labeling indices that the cell population which was released from the plateau-phase cultures remained in the G1 phase longer than the duration of the normal G1 phase in exponentially growing cells. When plateau-phase cultures were irradiated with 400 rad before subculture, the cells moved into the S phase approximately 4 hr later than did nonirradiated cells. Despite the G1/S delay, both irradiated and nonirradiated cell populations showed a similar rate of progression through the S phase. As determined by cumulative labeling indices, the fraction of cells which remained in G1 up to 120 hr post-subculture (G1 block) increased linearly with X-ray doses. There was no measurable X-ray-induced G1 delay or G1 block in cells irradiated after subculture at the G1/S border during semi-synchronous growth.


Comparative Evaluation of Plasma Bile Acids, Dehydroepiandrosterone Sulfate, Hexadecanedioate, and Tetradecanedioate with Coproporphyrins I and III as Markers of OATP Inhibition in Healthy Subjects.
Multiple endogenous compounds have been proposed as candidate biomarkers to monitor organic anion transporting polypeptide (OATP) function in preclinical species or humans. Previously, we demonstrated that coproporphyrins (CPs) I and III are appropriate clinical markers to evaluate OATP inhibition and recapitulate clinical drug-drug interactions (DDIs). In the present study, we investigated bile acids (BAs) dehydroepiandrosterone sulfate (DHEAS), hexadecanedioate (HDA), and tetradecanedioate (TDA) in plasma as endogenous probes for OATP inhibition and compared these candidate probes to CPs. All probes were determined in samples from a single study that examined their behavior and their association with rosuvastatin (RSV) pharmacokinetics after administration of an OATP inhibitor rifampin (RIF) in healthy subjects. Among endogenous probes examined, RIF significantly increased maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC)(0-24h) of fatty acids HDA and TDA by 2.2- to 3.2-fold. For the 13 bile acids in plasma examined, no statistically significant changes were detected between treatments. Changes in plasma DHEAS did not correlate with OATP1B inhibition by RIF. On the basis of the magnitude of effects for the endogenous compounds that demonstrated significant changes from baseline over interindividual variations, the overall rank order for the AUC change was found to be CP I > CP III > HDA ≈ TDA ≈ RSV > > BAs. Collectively, these results reconfirmed that CPs are novel biomarkers suitable for clinical use. In addition, HDA and TDA are useful for OATP functional assessment. Since these endogenous markers can be monitored in conjunction with pharmacokinetics analysis, the CPs and fatty acid dicarboxylates, either alone or in combination, offer promise of earlier diagnosis and risk stratification for OATP-mediated DDIs.


Norditerpenoids and Dinorditerpenoids from the Seeds of Podocarpus nagi as Cytotoxic Agents and Autophagy Inducers.
Nine new norditerpenoids and dinorditerpenoids, 2-oxonagilactone A (1), 7β-hydroxynagilactone D (2), nagilactones K and L (3 and 4), 3β-hydroxynagilactone L (5), 2β-hydroxynagilactone L (6), 3-epi-15-hydroxynagilactone D (7), 1α-chloro-2β,3β,15-trihydroxynagilactone L (8), and 15-hydroxynagilactone L (9), were isolated from the seeds of Podocarpus nagi, along with eight known analogues. The structures of the new compounds were established based on detailed NMR and HRESIMS analysis, as well as from their ECD spectra. The absolute configuration of the known compound 1-deoxy-2α-hydroxynagilactone A (16) was confirmed by single-crystal X-ray diffraction. All of the isolates were tested for their cytotoxic activities against cancer cells. The results indicated that compounds 4 and 6, as well as several known compounds, displayed cytotoxicity against A2780 and HEY cancer cells. Among the new compounds, 2β-hydroxynagilactone L (6) showed IC50 values of less than 2.5 μM against the two cell lines used. Furthermore, compound 6 induced autophagic flux in A2780 cells, as evidenced by an enhanced expression level of the autophagy marker phosphatidylethanolamine-modified microtubule-associated protein light-chain 3 (LC3-II) and increased mRFP-GFP-LC3 puncta. Also, compound 6 activated the c-Jun N-terminal kinase (JNK) pathway, while pretreatment with the JNK inhibitor SP600125 decreased compound 6-induced autophagy.


Analyses of the structure of NORs in two species of South American Sorubiminae fishes (Siluriformes) by means of several cytogenetic techniques.
Several cytogenetic techniques (AgNOR, C- G- and RE bandings, DAPI, CMA3 and FISH) were applied in order to analyze the structure and variability of NORs in the fish species Steindachneridion melanodermatum and S. scripta. Ag-NORs were observed on the short arm of the first acrocentric chromosome pair, coincidentally with a strong C-positive band on a large secondary constriction. In addition, NORs showed bright fluorescent signals when stained with CMA3 and treated for FISH with rDNA 18S. However, they showed negative coloration after G- and restriction enzyme banding and DAPI staining. The results evidence a substantial size polymorphism in these regions. The NOR bearing chromosomes in both species may be considered homologues because they maintain conserved characteristics, such as being interspersed with a GC-rich heterochromatin and possessing target sequences for AluI, BamHI and EcoRI.


Attentional retraining procedures: manipulating early or late components of attentional bias?
According to cognitive models of anxiety disorders, attentional bias for threatening information is a vulnerability factor to the etiology and maintenance of anxiety. A recently developed methodology to reduce attentional bias has been found to reduce emotional reactivity and anxiety. The present study aimed at identifying the effects of this attentional bias reduction on early and later stages of threat processing. Undergraduates were allocated to an attentional bias reduction (n = 23) versus control condition (n = 25). It was found that attentional bias reduction influenced late but not early stages of threat processing. This finding is of theoretical importance in relation to studies on the causal role of attentional bias and emotional reactivity. Moreover, the present findings also bear relevance to the clinical application of attentional retraining procedures.


Three-dimensional cardiac microtissues composed of cardiomyocytes and endothelial cells co-differentiated from human pluripotent stem cells.
Cardiomyocytes and endothelial cells in the heart are in close proximity and in constant dialogue. Endothelium regulates the size of the heart, supplies oxygen to the myocardium and secretes factors that support cardiomyocyte function. Robust and predictive cardiac disease models that faithfully recapitulate native human physiology in vitro would therefore ideally incorporate this cardiomyocyte-endothelium crosstalk. Here, we have generated and characterized human cardiac microtissues in vitro that integrate both cell types in complex 3D structures. We established conditions for simultaneous differentiation of cardiomyocytes and endothelial cells from human pluripotent stem cells following initial cardiac mesoderm induction. The endothelial cells expressed cardiac markers that were also present in primary cardiac microvasculature, suggesting cardiac endothelium identity. These cell populations were further enriched based on surface markers expression, then recombined allowing development of beating 3D structures termed cardiac microtissues. This in vitro model was robustly reproducible in both embryonic and induced pluripotent stem cells. It thus represents an advanced human stem cell-based platform for cardiovascular disease modelling and testing of relevant drugs.


Anaesthesia for a minor procedure in a patient with fontan physiology.
Fontan procedure is a palliative surgery done for patients born with single ventricle physiology. An understanding of the hemodynamic alterations in such a patient is important for successful perioperative management. We have discussed the anaesthetic considerations in a 12 year-old girl with complex congenital heart disease ultimately palliated by a Fontan operation, who was posted for Botox injections for upper limb spasticity under general anaesthesia.


Detecting adverse events for patient safety research: a review of current methodologies.
Promoting patient safety is a national priority. To evaluate interventions for reducing medical errors and adverse event, effective methods for detecting such events are required. This paper reviews the current methodologies for detection of adverse events and discusses their relative advantages and limitations. It also presents a cognitive framework for error monitoring and detection. While manual chart review has been considered the "gold-standard" for identifying adverse events in many patient safety studies, this methodology is expensive and imperfect. Investigators have developed or are currently evaluating, several electronic methods that can detect adverse events using coded data, free-text clinical narratives, or a combination of techniques. Advances in these systems will greatly facilitate our ability to monitor adverse events and promote patient safety research. But these systems will perform optimally only if we improve our understanding of the fundamental nature of errors and the ways in which the human mind can naturally, but erroneously, contribute to the problems that we observe.


Cancer risk in users of calcium channel blockers.
Ca2+ channel blockers may cause cancer by inhibiting apoptosis or reducing intracellular Ca2+ in certain tissues. Recent findings suggest that drug users are at increased risk for cancer in general and for colon cancer in particular. We conducted a study in one Danish county of 17911 patients who received at least one prescription of Ca2+ channel blockers between 1 January 1991 and 31 December 1993. The patients were identified from records in the National Health Insurance Program, which refunds part of the price of such drugs. Cancer occurrence and rate were determined by use of the files of the Danish Cancer Registry and compared with county-specific incidence rates for various categories of cancer. During the follow-up period of up to 3 years, 412 cancers were observed among users of Ca2+ channel blockers, compared with 414 expected, to yield an age- and sex-standardized incidence ratio (SIR) of 1.00 (95% confidence interval, 0.90 to 1.10). There was no indication of an excess risk in the subgroup of likely long-term users or users of specific drugs. The SIR of colon cancer, a site of a priori interest, was 0.8 (95% confidence interval, 0.5 to 1.1) on the basis of 34 cases. Although the results are reassuring, the lack of association could reflect the relatively short follow-up after registration in the prescription database. Continued monitoring of cancer risk is planned.


Differential expression of laminin isoform (alpha2), integrins (alpha3beta1 and alpha6beta4) and cytokeratin 20 in H. pylori gastritis.
The expression of laminin-1 chains (beta1 and gamma1), laminin-2 (merosin), integrin receptors to laminin (alpha3beta1 and alpha6beta4) and cytokeratin (CK20) were studied by immunohistochemical methods in gastric biopsies from antrum of 25 patients. H. pylori gastritis was found in 19 cases and intestinal metaplasia (IM) in four from these 19. Another 13 biopsies, all with IM were immunostained to laminin-2. Laminin-1 chains in normal and gastritis areas without IM were expressed as a strong, linear and continuous deposit in the basement membranes of the superficial and glandular epithelium. In metaplastic glands the reactivity to laminin-1 chains was decreased. Merosin was discontinuous when a moderate to accentuated H. pylori glandular colonization was present. Samples with IM were negative to laminin-2. The alpha3beta1 and alpha6beta4 integrins were negative only in IM gastric biopsies. The CK20 immunoreactivity was strong and homogeneous in the cells at the tip and the upper portion of foveolae in normal areas and in gastritis with IM the reactivity to CK 20 was heterogeneous. A differential expression of laminin isoforms is related to inflammation and subsequent IM caused by H. pylori. The alterations of alpha3beta1 and alpha6beta4 parallel both modifications in merosin and CK20 expression in H. pylori chronic gastritis.


Microfluidic sampling system for tissue analytics.
We have developed a microfluidics based sampling system for tissue analytics. The proof-of-concept of the sampling system was demonstrated by extracting lipid samples from tissue biopsies. The sample collection system consists of a disposable silicon based multiport microneedle integrated with polymer microfluidics. The polymethyl methacrylate polymer microfluidic chip has a 10 μl sample reservoir and actuation membranes for liquid pumping. A special automated robotic system was developed to control the positioning of the needle and the sampling procedure on preselected spots on the tissue. Real breast cancer tissue samples were used to test the feasibility of the sampling system. We successfully measured indicative cancer biomarkers from the tissue surface. Phosphatidylcholine and phosphoethanolamine were extracted from the tissue membrane with methyl tert-butyl ether solvent and detected by mass spectrometry. In the future, this tool could be used in characterization of preoperative biopsies and tumour tissues removed during surgery.


Worry and Rumination in Generalized Anxiety Disorder and Obsessive Compulsive Disorder.
Ample work has already been conducted on worry and rumination as negative thought processes involved in the etiology of most of the anxiety and mood related disorders. However, minimal effort has been exerted to investigate whether one type of negative thought process can make way for another type of negative thought process, and if so, how it subsequently results in experiencing a host of symptoms reflective of one or the other type of psychological distress. Therefore, the present study was taken up to investigate whether rumination mediates the relationship between worry and generalized anxiety disorder (GAD), and between worry and obsessive compulsive disorder (OCD) in two clinical groups. Self-report questionnaires tapping worry, rumination, generalized anxiety disorder (GAD), and obsessive compulsive disorder (OCD) were administered to a clinical sample of 60 patients aged 30-40. Worry, rumination, generalized anxiety disorder (GAD), and obsessive compulsive disorder (OCD) correlated substantially with each other, however, rumination did not mediate the relationship between worry and generalized anxiety disorder (GAD) and between worry and obsessive compulsive disorder (OCD). We also analyzed differences of outcome variables within two clinical groups. These results showed that worry and rumination were significantly different between GAD and OCD groups.


Lupus Nephritis in Tunisian Children: Predictive Factors of Poor Outcomes.
Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder of unknown etiology. Lupus nephritis (LN) is one of the most severe clinical manifestations observed in patients with SLE; it is more frequent and more severe in children than in adults. The aim of our study was to assess the predictive factors of poor outcomes in Tunisian children with LN. This was a multicenter retrospective observational study on 40 pediatric patients with biopsy-proven LN from five nephrology departments in Tunisia. The patients were 12.33 ± 3.3 years of age at the time of their kidney biopsy. Eleven patients developed end-stage renal disease (ESRD) (27.5%), and seven patients died. Overall, 18 (45%) patients reached our composite endpoint (ESRD or death). An age at diagnosis of more than 14 years, elevated serum creatinine at the time of the kidney biopsy, the existence of wire loops, thromboembolic complications as well as infectious complications are the most important clinical features associated with an increased risk of ESRD. Predictive factors of death were a baseline creatinine level of more than 2.26 mg/dL, a high proteinuria at baseline, fibrous crescents determined by renal biopsy, thromboembolic complications, infectious compli-cations, and ESRD. In summary, our results suggest that early and appropriate management is the best guarantee of a good renal outcome in children with LN.


Paradoxical roles of dual oxidases in cancer biology.
Dysregulated oxidative metabolism is a well-recognized aspect of cancer biology, and many therapeutic strategies are based on targeting cancers by altering cellular redox pathways. The NADPH oxidases (NOXes) present an important enzymatic source of biological oxidants, and the expression and activation of several NOX isoforms are frequently dysregulated in many cancers. Cell-based studies have demonstrated a role for several NOX isozymes in controlling cell proliferation and/or cell migration, further supporting a potential contributing role for NOX in promoting cancer. While various NOX isoforms are often upregulated in cancers, paradoxical recent findings indicate that dual oxidases (DUOXes), normally prominently expressed in epithelial lineages, are frequently suppressed in epithelial-derived cancers by epigenetic mechanisms, although the functional relevance of such DUOX silencing has remained unclear. This review will briefly summarize our current understanding regarding the importance of reactive oxygen species (ROS) and NOXes in cancer biology, and focus on recent observations indicating the unique and seemingly opposing roles of DUOX enzymes in cancer biology. We will discuss current knowledge regarding the functional properties of DUOX, and recent studies highlighting mechanistic consequences of DUOX1 loss in lung cancer, and its consequences for tumor invasiveness and current anticancer therapy. Finally, we will also discuss potentially unique roles for the DUOX maturation factors. Overall, a better understanding of mechanisms that regulate DUOX and the functional consequences of DUOX silencing in cancer may offer valuable new diagnostic insights and novel therapeutic opportunities.


On the way to Jupiter: psychological dimensions of the Galileo mission.
Emotions are a seldom-studied facet of the creative process in science and engineering. This paper describes a study of emotions in scientists and engineers on the Galileo mission to Jupiter, at the Jet Propulsion Laboratory in Pasadena, California, from 1987-90. Although the spacecraft was finally launched in 1989, and is now en route to Jupiter, the Callenger Shuttle accident severely threatened the Project's survival in 1986, placing many people under serious stress, and triggering depression in some. The paper describes the nature of the depressions (an overwhelming sense of futility), how people coped with the associated problems and emotions (social support was a critical variable), and how the depressions resolved. The findings have implications for future interrupted missions: managers can ease, and possibly help end, such depressions by empathizing with the experience of futility, by helping people to make significant shifts in task or position within a project, and by recognizing interim aachievement.


Non-sterilizing, Infection-Permissive Vaccination With Inactivated Influenza Virus Vaccine Reshapes Subsequent Virus Infection-Induced Protective Heterosubtypic Immunity From Cellular to Humoral Cross-Reactive Immune Responses.
Conventional influenza vaccines aim at the induction of virus-neutralizing antibodies that provide with sterilizing immunity. However, influenza vaccination often confers protection from disease but not from infection. The impact of infection-permissive vaccination on the immune response elicited by subsequent influenza virus infection is not well-understood. Here, we investigated to what extent infection-permissive immunity, in contrast to virus-neutralizing immunity, provided by a trivalent inactivated virus vaccine (TIV) modulates disease and virus-induced host immune responses after sublethal vaccine-matching H1N1 infection in a mouse model. More than one TIV vaccination was needed to induce a serum HI titer and provide sterilizing immunity upon homologous virus infection. However, single TIV administration provided infection-permissive immunity, characterized by lower viral lung titers and faster recovery. Despite the presence of replicating virus, single TIV vaccination prevented induction of pro-inflammatory cyto- and chemokines, alveolar macrophage depletion as well as the establishment of lung-resident B and T cells after infection. To investigate virus infection-induced cross-protective heterosubtypic immune responses in vaccinated and unvaccinated animals, mice were re-infected with a lethal dose of H3N2 virus 4 weeks after H1N1 infection. Single TIV vaccination did not prevent H1N1 virus infection-induced heterosubtypic cross-protection, but shifted the mechanism of cross-protection from the cellular to the humoral branch of the immune system. These results suggest that suboptimal vaccination with conventional influenza vaccines may still positively modulate disease outcome after influenza virus infection, while promoting humoral heterosubtypic immunity after virus infection.


Effect of Excipients on Salt Disproportionation during Dissolution: A Novel Application of In Situ Raman Imaging.
We have employed a bespoke setup combining confocal Raman microscopy and an ultraviolet-visible (UV-Vis) spectroscopy flow cell to investigate the effect of excipients on the disproportionation kinetics of Pioglitazone HCl (PioHCl) in tablets during dissolution. Three binary formulations of PioHCl, containing citric acid monohydrate (CA), lactose monohydrate (LM), or magnesium stearate (MgSt), respectively, were used as models to study the influence of excipients' physicochemical properties on the rate of salt disproportionation kinetics and dissolution performance in different aqueous pH environments. It was found that formulation excipients can induce or prevent salt disproportionation by modulating the microenvironmental pH regardless of the pH of the dissolution media. Incorporating CA in PioHCl tablets preserves the salt form and enhances the dissolution performance of the salt in the acidic medium (pH = 1.2). In contrast, LM and MgSt had a detrimental effect on in vitro drug performance by inducing salt disproportionation in the tablet during dissolution in the same acidic medium. Dissolution in the neutral medium (pH = 6.8) showed rapid formation of the free base upon contact with the dissolution medium. The Raman maps of the cross-sectioned tablets revealed the formation of a shell consisting of the free base around the edge of the tablet. This shell decreased the rate of penetration of the dissolution medium into the tablet, which had significant implications on the release of the API into the surrounding solution, as shown by the UV-vis absorption spectroscopy drug release data. Our findings highlight the utility of the Raman/UV-vis flow cell analytical platform as an advanced analytical technique to investigate the effect of excipients and dissolution media on salt disproportionation in real time. This methodology will be used to enhance our understanding of salt stability studies that may pave the way for more stable multicomponent formulations.


Directional excitatory input to direction-selective ganglion cells in the rabbit retina.
Directional responses in retinal ganglion cells are generated in large part by direction-selective release of γ-aminobutyric acid from starburst amacrine cells onto direction-selective ganglion cells (DSGCs). The excitatory inputs to DSGCs are also widely reported to be direction-selective, however, recent evidence suggests that glutamate release from bipolar cells is not directional, and directional excitation seen in patch-clamp analyses may be an artifact resulting from incomplete voltage control. Here, we test this voltage-clamp-artifact hypothesis in recordings from 62 ON-OFF DSGCs in the rabbit retina. The strength of the directional excitatory signal varies considerably across the sample of cells, but is not correlated with the strength of directional inhibition, as required for a voltage-clamp artifact. These results implicate additional mechanisms in generating directional excitatory inputs to DSGCs.


Aberrant cortisol regulations in bilateral macronodular adrenal hyperplasia: a frequent finding in a prospective study of 32 patients with overt or subclinical Cushing's syndrome.
ACTH-independent macronodular adrenal hyperplasia (AIMAH) is a rare and heterogeneous condition characterized by abnormal steroid production. Cortisol secretion can be regulated by aberrant hormone receptors. A large series of patients with AIMAH were evaluated to provide information on the prevalence and profile of aberrant regulations, in relation with the functional status. Thirty-two consecutive patients with AIMAH were prospectively studied: 10 had a Cushing's syndrome (CS), and 22 had a subclinical CS (SCS). A baseline endocrine evaluation was followed by an in vivo protocol in search of aberrant cortisol responses (seven provocative tests). An acute inhibition test with the somatostatin analog octreotide was also performed. At least one aberrant cortisol response was identified in 28 of 32 (87%) patients. The overall prevalence of aberrant responses was independent of the functional status. Responses to the upright posture and to metoclopramide were frequently observed (67 and 56% respectively). A glucagon response was frequently observed in the SCS group (58%). A cortisol inhibition by octreotide was specifically found in the three CS patients who positively responded to the mixed meal, and was observed also in 12 of 13 (92%) patients with SCS. Cortisol responses indicative of aberrant receptor expression were highly prevalent in AIMAH. Thorough phenotyping of AIMAH may help uncover the underlying pathophysiology.


[Antibiotic therapy of hospital-acquired pneumonia and its pharmacoeconomics].
Important hospital-acquired infections include pneumonia, mainly because of the increasing resistance of bacterial pathogens to antimicrobials and the associated potential failure of antibiotic therapy. The present study aimed at determining the most frequent etiological agents of hospital-acquired pneumonia (HAP) and assessing the relationship between 30-day mortality and adequacy of antibiotic therapy. Based on the obtained information, optimal patterns of antibiotic therapy were to be defined, including a pharmacoeconomic perspective. In patients with clinically confirmed HAP, bacterial etiological agents were identified, their susceptibility to antimicrobials was determined and statistical methods were used to assess the relationship between adequacy of antibiotic therapy and 30-day mortality. The study comprised 68 patients with clinically confirmed HAP. The most common etiological agents were strains of Pseudomonas aeruginosa (30.8 %), Klebsiella pneumoniae (23.1 %) and Burkholderia cepacia complex (15.4 %). Gram-negative bacteria accounted for 86.5 % of all bacterial pathogens. The overall mortality reached 42.5 %. In the subgroup of patients with inadequate antibiotic therapy, 30-day mortality was significantly higher (83.3 %) than in the subgroup with adequate therapy (30.0 %; p = 0.002). The risk for 30-day mortality was 2.78 times higher in case of inadequate antibiotic therapy (95%CI: 1.52-5.07). The proportion of Pseudomonas aeruginosa strains was significantly higher in the subgroup of patients with inadequate antibiotic therapy than in those with adequate therapy (67 % vs. 27 %; p = 0.032). Results of the present study suggest a significant relationship between mortality of patients with HAP and ineffective antibiotic therapy due to resistance of the bacterial pathogen. Thus, it is clear that initial antibiotic therapy must be based on qualified assumption of sufficient activity against the most common bacterial pathogens and results of surveillance of bacterial resistance in the relevant epidemiological unit. At the same time, however, it must be stressed that it is impossible to cover all potential variants of the etiological agents and their resistance phenotypes.


Analysis, requirements and development of a collaborative social and medical services data model.
In any medical and social service setting, patient data must be readily shared among multiple providers for delivery of expeditious, quality care. This paper describes the development and implementation of a generalized social and medical services data model for an ambulatory population. The model, part of the Collaborative Social and Medical Services System Project, is based on the data needs of the Baylor College of Medicine Teen Health Clinics and follows the guidelines of the ANSI HISPP/MSDS JWG for a Common Data Model. Design details were determined by informal staff interviews, operational observations, and examination of clinic guidelines and forms. The social and medical services data model is implemented using object-oriented data modeling techniques and will be implemented in C++ using an Object-Oriented Database Management System.


Mental health training scheme for police officers.
A previous study found that 61% of police officers said they had not received sufficient training to deal with problems involving mentally ill people. Training in this area can help police officers acquire awareness and understanding in order to aid the management of people with mental health problems. Police feedback on the training was largely positive, emphasising the potential for nationwide training on such issues.


Functional interaction between the integrin antagonist neutrophil inhibitory factor and the I domain of CD11b/CD18.
Neutrophil inhibitory factor (NIF) is a hookworm-derived glycoprotein ligand of the integrin CD11b/CD18 that inhibits human neutrophil function (Moyle, M., Foster, D. L., McGrath, D. E., Brown, S. M., Laroche, Y., De Meutter, J., Stanssens, P., Bogowitz, C. A., Fried, V. A., Ely, J. A., Soule, H. R., and Vlasuk, G. P. (1994) J. Biol. Chem. 269, 1008-10015). Here, we present evidence that recombinant NIF (rNIF) associates with the approximately 200-amino acid residue I domain of CD11b/CD18 and that this interaction is essential for inhibition of neutrophil function by NIF. First, radiolabeled rNIF binds to a recombinant glutathione S-transferase fusion protein that contains the CD11b I domain. This high affinity interaction has a partial dependence on divalent cations. The association of rNIF with the CD11b I domain is specific because 125I-rNIF does not bind either a glutathione S-transferase fusion protein that contains the I domain of the integrin CD11a/CD18 or recombinant glutathione S-transferase without the I domain. Second, the CD11b I domain fusion protein effectively competes with CD11b/CD18 on human neutrophils for 125I-rNIF binding. Third, the CD11b I domain fusion protein blocks the inhibition of certain neutrophil functions by rNIF, including adhesion of neutrophils to human endothelial cell monolayers and adhesion-dependent release of hydrogen peroxide from neutrophils. Specificity is demonstrated by the inability of the CD11a I domain fusion protein to block either rNIF binding to neutrophils or rNIF activity. Fourth, rNIF blocks the interaction between neutrophils and fibrinogen, a CD11b/CD18 ligand that is also thought to bind the I domain of CD11b. In contrast, rNIF does not appear to block the binding of factor X to CD11b/CD18 on neutrophils. These results suggest that CD11b/CD18 has multiple distinct binding sites for its cognate ligands, including, but not limited to, the I domain. NIF interferes with the binding of a subset of these CD11b/CD18 ligands in a highly selective manner.


The Antibiofilm Effect of a Medical Device Containing TIAB on Microorganisms Associated with Surgical Site Infection.
Surgical site infections (SSIs) represent the most common nosocomial infections, and surgical sutures are optimal surfaces for bacterial adhesion and biofilm formation. Staphylococcus spp., Enterococcus spp., and Escherichia coli are the most commonly isolated microorganisms. The aim of this research was to evaluate the antibiofilm activity of a medical device (MD) containing TIAB, which is a silver-nanotech patented product. The antibacterial effect was evaluated against Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212, and E. coli ATCC 25922 by assessing the minimum inhibitory concentration (MIC) by the Alamar Blue® (AB) assay. The antibiofilm effect was determined by evaluation of the minimum biofilm inhibitory concentration (MBIC) and colony-forming unit (CFU) count. Subsequently, the MD was applied on sutures exposed to the bacterial species. The antimicrobial and antibiofilm effects were evaluated by the agar diffusion test method, confocal laser scanning microscopy (CLSM), and scanning electron microscopy (SEM). The MIC was determined for S. aureus and E. faecalis at 2 mg/mL, while the MBIC was 1.5 mg/mL for S. aureus and 1 mg/mL for E. faecalis. The formation of an inhibition zone around three different treated sutures confirmed the antimicrobial activity, while the SEM and CLSM analysis performed on the MD-treated sutures underlined the presence of a few adhesive cells, which were for the most part dead. The MD showed antimicrobial and antibiofilm activities versus S. aureus and E. faecalis, but a lower efficacy against E. coli. Surgical sutures coated with the MD have the potential to reduce SSIs as well as the risk of biofilm formation post-surgery.


Low complication rate of sellar reconstruction by artificial dura mater during endoscopic endonasal transsphenoidal surgery.
To evaluate effect of sellar reconstruction during pituitary adenoma resection surgery by the endoscopic endonasal transsphenoidal approach using artificial cerebral dura mater patch.This was a retrospective study of 1281 patients who underwent endoscopic transsphenoidal resection for the treatment of pituitary adenomas between December 2006 and May 2014 at the Neurosurgery Department of the People's Liberation Army General Hospital. The patients were classified into 4 grades according to intraoperative cerebrospinal fluid (CSF) leakage site. All patients were followed up for 3 months by telephone and outpatient visits.One thousand seventy three (83.7%) patients underwent sellar reconstruction using artificial dura matter patched outside the sellar region (method A), 106 (8.3%) using artificial dura matter patched inside the sellar region (method B), and 102 (8.0%) using artificial dura matter and a mucosal flap (method C). Method A was used for grade 0-1 leakage, method B for grade 1 to 2 leakage, and method C for grade 2 to 3 leakage. During the 3-month follow-up, postoperative CSF leakage was observed in 7 patients (0.6%): 2 among patients who underwent method B (1.9%) and 5 among those who underwent method C (4.9%). Meningitis was diagnosed in 13 patients (1.0%): 2 among patients who underwent method A (0.2%), 4 among those who underwent method B (3.8%), and 7 among those who underwent method C (6.7%).Compared with other reconstruction methods, sellar reconstruction surgery that only use artificial dura mater as repair material had a low rate of complications.


A socioemotional intervention in a Latin American orphanage.
A pilot intervention that emphasized training and technical assistance to promote warm, sensitive, and responsive one-on-one caregiver-child interactions primarily during feeding and bathing/changing was implemented using regular staff in a depressed orphanage for children birth to approximately 8 years of age in Latin America. Despite a variety of unanticipated irregularities in the implementation of the intervention, many beyond the researchers' control, ward environments improved; caregivers displayed more warm, sensitive, and responsive interactions with children; and children improved an average of 13.5 developmental quotient (DQ) points after 4+ months' exposure to the completed intervention. Furthermore, 82% of the children had DQs greater than 70 before the intervention, but only 27.8% did so afterward. Although the training for all caregivers was aimed at children birth to 3 years, the number of different caregivers was reduced, and technical assistance was provided only to caregivers serving children less than 3 years, younger and older children (3-8 years) improved approximately the same amount. However, children who were transitioned from a younger to an older ward during the intervention improved less than did children who remained in either a younger or an older ward, the first evidence suggesting that the common orphanage practice of periodically graduating children from one homogeneous age group to another may impede their development. The study is consistent with others that have shown that orphanages can be changed, and increases primarily in warm, sensitive, responsive caregiver-child interactions can produce improvements in children's development.


[Comparison between rapid detection method of enzyme substrate technique and multiple-tube fermentation technique in water coliform bacteria detection].
To compare between rapid detection method of enzyme substrate technique and multiple-tube fermentation technique in water coliform bacteria detection. Using inoculated and real water samples to compare the equivalence and false positive rate between two methods. Results demonstrate that enzyme substrate technique shows equivalence with multiple-tube fermentation technique (P = 0.059), false positive rate between the two methods has no statistical difference. It is suggested that enzyme substrate technique can be used as a standard method for water microbiological safety evaluation.


Ligand-induced desensitization of B-cell membrane immunoglobulin-mediated Ca2+ mobilization and protein kinase C translocation.
Binding of ligand to B-cell membrane immunoglobulin (mIg) can lead to activation of a number of distinct biologic responses, including altered expression of genes encoding c-fos, c-myc, and Ia, as well as proliferation and immunologic tolerance. Tolerance could reflect a functional uncoupling of receptors from systems that generate intracellular second messengers (i.e., receptor desensitization). To better understand the molecular basis of immune regulation, we examined the ability of mIg to function as a signal transducer after the cell's initial contact with mIg-binding ligand. The results show that ligand binding to as little as 2-10% of mIgM or mIgD renders the cell unresponsive to ligand binding to the reciprocal isotype as judged by Ca2+ mobilization and protein kinase C translocation responses. This heterologous receptor desensitization lasts longer than 24 hr and does not reflect loss of receptor from the cell surface. Studies with the calcium ionophore ionomycin, 1,2-dioctanoyl-sn-glycerol, and the protein kinase inhibitor staurosporine indicate that both protein kinase C-dependent and protein kinase C-independent (staurosporine-insensitive) mechanisms mediate heterologous desensitization after mIg crosslinking.


Prostate-specific antigen and external beam radiation therapy in prostate cancer.
This study of 133 patients with localized prostate cancer (Stages A2 to C), treated by external beam radiation therapy (XRT), was undertaken for two reasons: (1) to investigate the usefulness of pretreatment serum prostate-specific antigen (PSA) levels in evaluating patients before XRT; and (2) to investigate post-XRT changes in PSA values and their likely clinical significance. It was found that pretreatment PSA values in patients with localized disease exhibit wide patient to patient variability with a greater than 100-fold difference between the lowest and highest values. Although mean PSA values were significantly higher in Stage C disease (51 patients; mean PSA, 17.3 ng/ml) than in Stage A2 disease (31 patients; mean PSA, 9.0 ng/ml), Stage B1 disease (23 patients; mean PSA, 9.1 ng/ml), or Stage B2 disease (28 patients; mean PSA, 10.6 ng/ml), individual values were of virtually no help in assigning individual patients to a clinical stage. PSA levels did not correlate with grade. After XRT, PSA values fell significantly and dramatically in virtually all patients (98%) by 3 months follow-up. Mean PSA fell from 12.5 to 2.6 ng/ml, and median PSA fell from 6.6 to 1.9 ng/ml. In most patients, PSA continued to fall up to 12 months after XRT and then stabilized at 21 months. Although PSA values fell dramatically after XRT, PSA was detectable in the serum of all patients. PSA values tended to transiently and mildly elevate during XRT. In a small proportion of patients, rising PSA values were observed after 6 months. The full significance of this requires further follow-up, of four such patients, one has relapsed. PSA is a more sensitive marker of prostatic radiation than prostatic acid phosphatase.