Emergency treatment of Graves' ophthalmopathy.
The ocular emergencies encountered in Graves' ophthalmopathy, namely optic neuropathy, corneal ulceration, subluxation of the globe, and severe periorbital oedema with chemosis have been discussed. Evaluation of the clinical signs and symptoms of these conditions, as well as their treatment, have been outlined. Of particular concern is the complaint of 'blurry vision' that may indicate the presence of optic neuropathy. Early recognition of this entity, with prompt referral to an ophthalmologist is important because there is an inverse relationship between duration of visual loss and efficacy of treatment. The ophthalmological evaluation of a patient with optic neuropathy may demonstrate decreased visual acuity, impaired colour perception, or an afferent pupillary defect. In addition, a visual field examination may be a helpful adjunctive test. Available therapy for optic neuropathy includes high-dose corticosteroids, supervoltage X-irradiation and orbital decompressive surgery. We have reviewed the literature concerning these modalities and outlined our approach to the treatment of optic neuropathy. In general, we recommend orbital decompression at an early stage for this condition. Another worrisome complaint is of 'eye pain'. In this case, distinction must be made between the causes that include ocular inflammation, corneal keratitis and corneal ulceration. The corneal ulceration is characterized by extreme eye pain and erythema, and may require surgical intervention. Severe ocular inflammation may respond well to a course of high-dose steroids. A combination of these ocular emergencies in a patient with Graves' ophthalmology necessitates careful consideration of the available treatment options.


Calculation of shielding door thicknesses for radiation therapy facilities using the ITS Monte Carlo program.
Shielding calculations for door thicknesses for megavoltage radiotherapy facilities with mazes are generally straightforward. To simplify the calculations, the standard formalism adopts several approximations relating to the average beam path, scattering coefficients, and the mean energy of the spectrum of scattered radiation. To test the accuracy of these calculations, the Monte Carlo program, ITS, was applied to this problem by determining the dose and energy spectrum of the radiation at the door for 4- and 10-MV bremsstrahlung beams incident on a phantom at isocenter. This was performed for mazes, one termed "standard" and the other a shorter maze where the primary beam is incident on the wall adjacent to the door. The peak of the photon-energy spectrum at the door was found to be the same for both types of maze, independent of primary beam energy, and also, in the case of the conventional maze, of the primary beam orientation. The spectrum was harder for the short maze and for 10 MV vs. 4 MV. The thickness of the lead door for a short maze configuration was 1.5 cm for 10 MV and 1.2 cm for 4 MV vs. approximately less than 1 mm for a conventional maze. For the conventional maze, the Monte Carlo calculation predicts the dose at the door to be lower than given by NCRP 49 and NCRP 51 by about a factor of 2 at 4 MV but to be the same at 10 MV. For the short maze, the Monte Carlo predicts the dose to be a factor of 3 lower for 4 MV and about a factor of 1.5 lower for 10 MV. Experimental results support the Monte Carlo findings for the short maze.


[The method of the integral evaluation of the behavioral depression in rats].
A new method of the evaluation of behavioral depression was developed based on a ranged scale of changes in a number of depressive symptoms in behavior and general state of animals. The method makes it possible to evaluate the individual expression of depressive symptoms in rats and can be used for revealing a correlation between the decrease in motivation level in depressive animals and alterations of some pathophysiological parameters.


Understanding the Origin of Enhanced Piezoelectric Response in PVDF Matrices with Embedded ZnO Nanoparticles, from Polarizable Molecular Dynamics Simulations.
The pervasive use of portable electronic devices, powered from rechargeable batteries, represents a significant portion of the electricity consumption in the world. A sustainable and alternative energy source for these devices would require unconventional power sources, such as harvesting kinetic/potential energy from mechanical vibrations, ultrasound waves, and biomechanical motion, to name a few. Piezoelectric materials transform mechanical deformation into electric fields or, conversely, external electric fields into mechanical motion. Therefore, accurate prediction of elastic and piezoelectric properties of materials, from the atomic structure and composition, is essential for studying and optimizing new piezogenerators. Here, we demonstrate the application of harmonic-covalent and reactive force fields (FF), Dreiding and ReaxFF, respectively, coupled to the polarizable charge equilibration (PQEq) model for predicting the elastic moduli and piezoelectric response of crystalline zinc oxide (ZnO) and polyvinylidene difluoride (PVDF). Furthermore, we parametrized the ReaxFF atomic interactions for Zn-F in order to characterize the interfacial effects in hybrid PVDF matrices with embedded ZnO nanoparticles (NPs). We capture the nonlinear piezoelectric behavior of the PVDF-ZnO system at different ZnO concentrations and the enhanced response that was recently observed experimentally, between 5 and 7 wt % ZnO concentrations. From our simulation results, we demonstrate that the origin of this enhancement is due to an increase in the total atomic stress distribution at the interface between the two materials. This result provides valuable insight into the design of new and improved piezoelectric nanogenerators and demonstrates the practical value of these first-principles based modeling methods in materials science.


Identification of HLA DR7-restricted epitopes from human telomerase reverse transcriptase recognized by CD4+ T-helper cells.
CD4+ T cells play critical roles in initiating, regulating, and maintaining antitumor immune responses. One way to improve current tumor vaccines that mainly induce CTLs would be to activate antigen-specific CD4+ T cells that recognize MHC class II restricted tumor associated antigens. Human telomerase reverse transcriptase (hTRT) is preferentially expressed by various tumors and, therefore, could be a universal tumor antigen. In this study, we used a combined approach of using the prediction software TEPITOPE to select class II epitope candidates and in vitro T-cell biological analysis to identify class II-restricted epitope(s) in hTRT. We first identified several HLA-DR7-restricted class-II epitope candidates in hTRT by examining human T-cell responses to synthetic peptides. We then characterized these HLA-DR7-restricted hTRT epitope candidates by establishing and analyzing peptide-specific T-cell clones. It was demonstrated that CD4+ T cells specific for the HLA-DR7-restricted hTRT(672) epitope (RPGLLGASVLGLDDI) can respond to naturally processed hTRT proteins. Furthermore, the hTRT(672)-specific T cells recognized hTRT antigen from various tumors, including prostate cancer, breast cancer, melanoma, and leukemia. Thus, the identification of the naturally processed HLA-DR7-restricted hTRT epitope, together with the previous finding of class I-restricted hTRT epitopes, provide a basis for the combined application of class I- and II-restricted hTRT epitopes to induce potent, long-term CD4+ and CD8+ T-cell responses against a broad spectrum of tumors.


Causal relationships between frequency bands of extracellular signals in visual cortex revealed by an information theoretic analysis.
Characterizing how different cortical rhythms interact and how their interaction changes with sensory stimulation is important to gather insights into how these rhythms are generated and what sensory function they may play. Concepts from information theory, such as Transfer Entropy (TE), offer principled ways to quantify the amount of causation between different frequency bands of the signal recorded from extracellular electrodes; yet these techniques are hard to apply to real data. To address the above issues, in this study we develop a method to compute fast and reliably the amount of TE from experimental time series of extracellular potentials. The method consisted in adapting efficiently the calculation of TE to analog signals and in providing appropriate sampling bias corrections. We then used this method to quantify the strength and significance of causal interaction between frequency bands of field potentials and spikes recorded from primary visual cortex of anaesthetized macaques, both during spontaneous activity and during binocular presentation of naturalistic color movies. Causal interactions between different frequency bands were prominent when considering the signals at a fine (ms) temporal resolution, and happened with a very short (ms-scale) delay. The interactions were much less prominent and significant at coarser temporal resolutions. At high temporal resolution, we found strong bidirectional causal interactions between gamma-band (40-100 Hz) and slower field potentials when considering signals recorded within a distance of 2 mm. The interactions involving gamma bands signals were stronger during movie presentation than in absence of stimuli, suggesting a strong role of the gamma cycle in processing naturalistic stimuli. Moreover, the phase of gamma oscillations was playing a stronger role than their amplitude in increasing causations with slower field potentials and spikes during stimulation. The dominant direction of causality was mainly found in the direction from MUA or gamma frequency band signals to lower frequency signals, suggesting that hierarchical correlations between lower and higher frequency cortical rhythms are originated by the faster rhythms.


Biochemical indices of renal osteodystrophy in dialysis patients on the island of Malta.
Renal osteodystrophy (ROD) has never been studied on the small Mediterranean island of Malta, which has a largely inbred population. The genetic contribution to the pattern of renal osteodystrophy is being increasingly recognized. We were, thus, interested in studying indices of bone turnover in Maltese end stage renal failure patients. Sixty unselected patients, representing 65% of all patients undergoing dialysis in the island's renal unit, were prospectively investigated over a period of 5 months with respect to symptoms, calcium/phosphate chemistry, intact parathyroid hormone (iPTH) and bone alkaline phosphatase (bAP). Bone histomorphometry, which is the gold standard in the diagnosis of ROD, was not within the reach of our small unit. Biochemical markers may not be as sensitive and specific as bone biopsy for individual patient diagnosis of ROD sub-type but they can give a fairly good indication of the spectrum of bone turnover on a population basis. The optimum combination of biochemical marker cut-offs available from studies in the literature was then employed to estimate bone turnover. The following biochemical picture emerged: 42% had iPTH < 79.7 pg/ml (which cut off has a reported specificity of 93.7% for low turnover bone disease), 45% had iPTH > 100 pg/ml and bAP > 10 ng/ml (which combined cut off has a reported specificity of 100% for high turnover bone disease), while 13% could not be classified (ie had intermediate values). Based on biochemical data, the pattern of bone turnover seems to be comparable to the European average. Further indepth study using bone histomorphometry is warranted.


The landscape genetics of infectious disease emergence and spread.
The spread of parasites is inherently a spatial process often embedded in physically complex landscapes. It is therefore not surprising that infectious disease researchers are increasingly taking a landscape genetics perspective to elucidate mechanisms underlying basic ecological processes driving infectious disease dynamics and to understand the linkage between spatially dependent population processes and the geographic distribution of genetic variation within both hosts and parasites. The increasing availability of genetic information on hosts and parasites when coupled to their ecological interactions can lead to insights for predicting patterns of disease emergence, spread and control. Here, we review research progress in this area based on four different motivations for the application of landscape genetics approaches: (i) assessing the spatial organization of genetic variation in parasites as a function of environmental variability, (ii) using host population genetic structure as a means to parameterize ecological dynamics that indirectly influence parasite populations, for example, gene flow and movement pathways across heterogeneous landscapes and the concurrent transport of infectious agents, (iii) elucidating the temporal and spatial scales of disease processes and (iv) reconstructing and understanding infectious disease invasion. Throughout this review, we emphasize that landscape genetic principles are relevant to infection dynamics across a range of scales from within host dynamics to global geographic patterns and that they can also be applied to unconventional 'landscapes' such as heterogeneous contact networks underlying the spread of human and livestock diseases. We conclude by discussing some general considerations and problems for inferring epidemiological processes from genetic data and try to identify possible future directions and applications for this rapidly expanding field.


Mtap2 is a constituent of the protein network that regulates twik-related K+ channel expression and trafficking.
Twik-related K+ (TREK) channels produce background currents that regulate cell excitability. In vivo, TREK-1 is involved in neuronal processes including neuroprotection against ischemia, general anesthesia, pain perception, and mood. Recently, we demonstrated that A-kinase anchoring protein AKAP150 binds to a major regulatory domain of TREK-1, promoting drastic changes in channel regulation by polyunsaturated fatty acids, pH, and stretch, and by G-protein-coupled receptors to neurotransmitters and hormones. Here, we show that the microtubule-associated protein Mtap2 is another constituent of native TREK channels in the brain. Mtap2 binding to TREK-1 and TREK-2 does not affect directly channel properties but enhances channel surface expression and current density. This effect relies on Mtap2 binding to microtubules. Mtap2 and AKAP150 interacting sites in TREK-1 are distinct and both proteins can dock simultaneously. Their effects on TREK-1 surface expression and activation are cumulative. In neurons, the three proteins are simultaneously detected in postsynaptic dense bodies. AKAP150 and Mtap2 put TREK channels at the center of a complex protein network that finely tunes channel trafficking, addressing, and regulation.


Antiviral activity of 1-docosanol, an inhibitor of lipid-enveloped viruses including herpes simplex.
This article reports that 1-docosanol, a 22-carbon-long saturated alcohol, exerts a substantial inhibitory effect on replication of certain viruses (e.g., herpes simplex virus and respiratory syncytial virus) within primary target cells in vitro. To study the basis for its viral inhibitory activity, a suspension of 1-docosanol was formulated in an inert and nontoxic surfactant, Pluronic F-68; this suspension exerted potent inhibitory activity on the ability of susceptible viruses to infect cultured target cells. Susceptible viruses included wild-type herpes simplex viruses 1 and 2 as well as acyclovir-resistant herpes simplex virus 2 and also respiratory syncytial virus--all of which are lipid-enveloped. In contrast, nonenveloped poliovirus was not susceptible to the inhibitory action of 1-docosanol. Although the precise mechanism has yet to be defined, current evidence suggests that 1-docosanol inhibits viral replication by interfering with the early intracellular events surrounding viral entry into target cells. It is possible that interaction between the highly lipophilic compound and components of target cell membranes renders such target cells less susceptible to viral fusion and/or entry. If this mechanism proves to be correct, 1-docosanol may provide a broad spectrum activity against many different viruses, especially those with lipid-containing envelopes.


Solar drying and organoleptic characteristics of two tropical African fish species using improved low-cost solar driers.
This study was done to evaluate the drying performance, efficiency, and effectiveness of five different types of improved low-cost solar driers in terms of moisture loss from two tropical African fish species Clarias gariepinus (African sharp tooth catfish) and Oreochromis niloticus (Nile tilapia) and testing the organoleptic characteristics of the dried samples. The driers used were made from plastic, aluminum, glass, glass with black igneous stone, and mosquito net, with traditional direct open-sun drying as a control. A significant (P < 0.05) decrease in weight resulting from moisture loss in the two fish species was observed in all the driers, with the highest reduction occurring in the glass drier containing black stone. The rate of weight loss was faster in the first 4 days of drying with black stone-inserted glass drier showing the fastest drying rate with a constant weight in C. gariepinus attained on the 11th day and in O. niloticus on the eighth day. The slowest drier was plastic where a constant weight of the species were recorded on and 13th day and 11th day, respectively. Volunteers were used to assess the organoleptic characteristics of the dried samples and they showed lowest acceptability for the open-sun drying, while samples from the glass drier containing black stone had the highest acceptability in terms of the taste, flavor, appearance, texture, odor, palatability, and shelf-life. The low-cost solar driers were effective found in removing water from the fish resulting in significant loss of weight and moisture. The highest drying time, efficient performance, drying effectiveness, and high acceptability of the organoleptic parameters of the dried products from the black stone-inserted glass drier were due to the ability of the glass and the black stone to retain, transmit, and radiate heat to the fish sample all the time (day and night). These low-cost driers are simple to construct, materials for its construction readily available, easy to maintain and operate, hygienic in use, reliable, effective, occupies less area, dry products faster with increased shelf-life, save man-hour, user-friendly, use renewable energy, protect the drying samples from filthiness, wetness, and invasion by pests, insects, and microbes, with well-dried, high-quality, and better preserved final products. The adoption and use any of these low-cost solar driers by artisanal fishermen and general household in sub-Saharan Africa will not only help in reducing post catch losses, but also ensure food safety and security as there is abundant solar energy in these sub-Saharan African tropical countries for the operation of the driers.


State of emergency: behavior of gerbils is affected by the hunger state of their predators.
Predator-prey interactions are usually composed of behaviorally sophisticated games in which the values of the strategies of foraging prey individuals may depend on those of their predators, and vice versa. Therefore, any change in the behavior of the predator should result in changes to the behavior of the prey. However, this key prediction has rarely been tested. To examine the effects of the predator state on prey behavior, we manipulated the state of captive Barn Owls, Tyto alba, and released them into an enclosure containing Allenby's gerbils, Gerbillus andersoni allenbyi, a common prey of the owls. The owls were significantly more active when hungry. In response, the gerbils altered their behavior according to the state of the owl. When the owl was hungry, the gerbils visited fewer food patches, foraged in fewer patches, and harvested less food from each patch. Moreover, the gerbils kept their foraging bouts closer to their burrow, which reduced the overlap among foraging ranges of individual gerbils. Thus, changes in the state of the predator affect the foraging behavior of its prey and can also mediate competition among prey individuals.


Tissue solidification in coping with digestive tract bleeding: hemostatic effect of local injection of 99.5% ethanol.
Tatsuka et al. reported a local injection of 95% ethanol as a new endoscopic treatment of gastric protuberant lesions. In this method, the present author discovered that 99.5% ethanol injection has an excellent hemostatic effect. The author injected 99.5% ethanol into the cut-end of the stalk of 7 massively hemorrhaged cases encountered while performing double snare polypectomy. In all cases, the hemorrhage stopped within 5 or 15 min. In 9 patients with hemorrhagic gastric or duodenal ulcer who were judged at emergency endoscopic examination as needing some hemostatic treatment, an injection of 99.5% ethanol into the bleeding site achieved a satisfactory hemostasis in all of them. Ethanol injection into the surrounding tissue close to the bleeding vessels, a few injecting sites selected usually at 1 to 2 mm away from the bleeding vessels, 0.1 to 0.2 ml a time, could instantly suppress even the pulsatile bleeding with no hazards. If this method is used carefully with endoscopic skill, this should become the first choice for the gastro-intestinal hemorrhage except varices.


Inhibition effect of phenyl compounds from the Oryza sativa roots on melanin production in murine B16-F10 melanoma cells.
Five phenyl compounds, vanillin (1), methyl trans-ferulate (2), trans-p-coumaric acid methyl ester (3), N-benzoyltryptamine (4), and N-(trans-cinnamoyl)tryptamine (5), were isolated from the roots of Oryza sativa L. and identified on the basis of spectroscopic data. Compounds 3 and 5 showed strong inhibition effect on melanin production in murine B16-F10 melanoma cells and tyrosinase activity. Also, the quantitative analysis of the compounds was carried out using LC/MS/MS experiment. Compounds 3 and 5 could be used as skin-whitening agents.


Simvastatin inhibits IL-17 secretion by targeting multiple IL-17-regulatory cytokines and by inhibiting the expression of IL-17 transcription factor RORC in CD4+ lymphocytes.
Statins, extensively used as cholesterol-lowering agents, have recently been identified as immunomodulatory agents. This study investigated the statins' mechanisms that target the autoimmune response in humans, and evaluated their therapeutic potential in multiple sclerosis. Our results demonstrated statin-mediated increases in suppressor of cytokine secretion (SOCS) 3 and suppressor of cytokine secretion 7, which negatively regulate the STAT/JAK signal transduction pathway and IL-6 and IL-23 gene expression in monocytes. Simvastatin also induced IFN-gamma, IL-4, and IL-27 production in monocytes, which together inhibited IL-17 transcription and secretion in CD4(+) T cells. IL-17-producing CD4(+) cells, referred to as Th17 cells, have recently been found to play a central role in the development of autoimmune diseases. Furthermore, simvastatin directly inhibited the expression of retinoic acid-related orphan nuclear hormone receptor C, a transcription factor that controls IL-17 production in CD4(+) T cells. This effect was reversed by mevalonic acid, a downstream metabolite of 3-hydroxy-3-methylglutaryl CoA reductase, confirming that simvastatin's specific effect is through the inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase. These results provide evidence for the novel immunomodulatory mechanisms of statins, which selectively target the regulation of cytokine transcription involved in the development of the human autoimmune response. Based on the described immunomodulatory mechanisms, good safety profile and oral bioavailability, statins represent a promising therapeutic approach for multiple sclerosis and other chronic inflammatory diseases.


Toward a more humane intracerebral pathogenicity index that does not compromise virus pathogenicity ratings.
Determination of the intracerebral pathogenicity index (ICPI) of a virus requires tracking sick animals until death or until the eighth day of the standard observation period. A more humane procedure would be to painlessly kill sick animals, but such intervention in the standard protocol could compromise the rating of the virus. In this paper, a modified scoring system is proposed, whereby humanely killed animals are given a score that, on average, does not alter the ICPI. The variance of an animal's contribution to the optimum modified ICPI is never greater than the variance of its contribution to the standard ICPI.


TRPC2.
Trp2 was the second ortholog of the Drosophila trp gene to be identified. Whereas full-length TRPC2 transcripts have been cloned in a number of species including mice, rats, and New World monkeys, TRPC2 is a pseudogene in humans, apes, Old World monkeys, and in a number of other vertebrates. TRPC2 is highly expressed in the rodent VNO. It is also detectable at the protein level in murine erythroblasts, sperm, and brain and has been detected in other tissues by RT-PCR. Its activation by DAG and by erythropoietin has been described in greatest detail, and inhibition by Ca(2+)-calmodulin has been reported. The major demonstrated functions of TRPC2 are regulation of pheromone-evoked signaling in the rodent VNO, regulation of erythropoietin-stimulated calcium influx in murine erythroid cells, and ZP3-evoked calcium influx into sperm. Depletion of TRPC2 in knockout mice resulted in changes in behavior including altered sex discrimination and lack of male-male aggression. The red cells of TRPC2 knockout mice showed increased mean corpuscular volume, mean corpuscular hemoglobin, and hematocrit and reduced mean corpuscular hemoglobin concentration. TRPC2-depleted red cells were resistant to oxidative stress-induced hemolysis.


Microvessel density as a prognostic factor in esophageal squamous cell cancer patients: A meta-analysis.
To date, literature has emerged that shows contradictory results about the prognostic role of microvessel density (MVD) in esophageal squamous cell cancer (ESCC). The aim of the study set out to evaluate the correlation between MVD and the prognosis of ESCC. Identified publications from various databases were obtained and reviewed. A meta-analysis was performed to evaluate the prognostic role of MVD among ESCC patients. A total of 11 eligible studies containing 891 ESCC cases were included in the meta-analysis. The pooled hazard ratio for overall survival was 2.39 (95% confidence interval 1.92-2.96, P < .001). Heterogeneity among the studies was not significant, and publication bias was not found. Subgroup analyses were also performed on different issues, such as districts, antibodies, and median age. High MVD is a prognostic factor among ESCC that indicated worse prognosis in these patients. More studies are needed, and through abundant evidence, the topic could be re-evaluated by then.


Exercise prescription for people with mental illness: an evaluation of mental health professionals' knowledge, beliefs, barriers, and behaviors.
The aim of this study was to understand the knowledge, beliefs, barriers, and behaviors of mental health professionals about physical activity and exercise for people with mental illness. The Portuguese version of The Exercise in Mental Illness Questionnaire was used to assess knowledge, beliefs, barriers, and behaviors about exercise prescription for people with mental illness in a sample of 73 mental health professionals (68.5% women, mean age = 37.0 years) from 10 Psychosocial Care Units (Centros de Atenção Psicossocial) in Porto Alegre and Canoas, state of Rio Grande do Sul, Brazil. Most of respondents had received no formal training in exercise prescription. Exercise ranked fifth as the most important treatment, and most of the sample never or occasionally prescribed exercise. The most frequently reported barriers were lack of training in physical activity and exercise prescription and social stigma related to mental illness. Professionals who themselves met recommended physical activity levels found fewer barriers to prescribing physical activity and did so with greater frequency. Exercise is underrated and underused as a treatment. It is necessary to include physical activity and exercise training in mental health curricula. Physically active professionals are more likely to prescribe exercise and are less likely to encounter barriers to doing so. Interventions to increase physical activity levels among mental health professionals are necessary to decrease barriers to and increase the prescription of physical activity and exercise for mental health patients.


The exposome in practice: Design of the EXPOsOMICS project.
EXPOsOMICS is a European Union funded project that aims to develop a novel approach to the assessment of exposure to high priority environmental pollutants, by characterizing the external and the internal components of the exposome. It focuses on air and water contaminants during critical periods of life. To this end, the project centres on 1) exposure assessment at the personal and population levels within existing European short and long-term population studies, exploiting available tools and methods which have been developed for personal exposure monitoring (PEM); and 2) multiple "omic" technologies for the analysis of biological samples (internal markers of external exposures). The search for the relationships between external exposures and global profiles of molecular features in the same individuals constitutes a novel advancement towards the development of "next generation exposure assessment" for environmental chemicals and their mixtures. The linkage with disease risks opens the way to what are defined here as 'exposome-wide association studies' (EWAS).


The role of indirect photolysis in limiting the persistence of crop protection products in surface waters.
The photodegradation of six crop protection products (CPPs) was studied in 16 natural waters collected from across the midwest of the United States under simulated sunlight to determine the significance of indirect photolysis. The rate of degradation of five of the CPPs was faster in irradiated natural waters than in buffer systems, with the effect particularly significant with the relatively photostable compounds propiconazole and prometryn. Degradation rates were correlated with the concentration of one or more photosensitizers, or ratios thereof, by means of a Pearson's correlation and linear regression analysis. It was found that the photodegradation of chlorotoluron, pinoxaden, propiconazole and prometryn were linked to the concentration of nitrate, pointing to a significant role of hydroxyl radical ((.)OH) as a reactive intermediate. Increased concentrations of dissolved organic carbon (DOC) and bicarbonate relative to nitrate were found to decrease the rate of degradation of these compounds, consistent with a quenching role. Chlorothalonil appeared to be rapidly degraded by means of the carbonate radical ((.)CO(3)(-)), whereas the photodegradation of emamectin was particularly complex. Overall, indirect photolysis significantly enhanced the rate of CPP degradation and fate models based on these experiments appear to offer more realism than those that only take into account direct photolysis.


Preparation and Characterization of Bioactive Chitosan Film Loaded with Cashew (Anacardium occidentale) Leaf Extract.
Chitosan is a biopolymer known for its rapid biodegradability and film-forming properties. This research aimed to synthesize and characterize chitosan films loaded with cashew leaf extract (CLE) obtained from immature and mature cashew leaves via aqueous and 70% ethanolic extraction methods. Freeze-dried CLE samples were dissolved in 50% dimethyl sulfoxide for in vitro analysis and chitosan film preparation. The total phenolic content of mature cashew leaves extracted in ethanol (MECLE) showed higher free radicle scavenging activity by a 2,2-diphenyl-1-picrylhydrazyl assay than the other extracts (p < 0.05). MECLE displayed a lower minimal inhibitory concentration, minimum fungal concentration, and higher zone of inhibition against Aspergillus niger compared to the other treatments (p < 0.05). Film-forming solutions were prepared using 2% chitosan, 2% chitosan with 5% mature cashew leaves extracted in deionized water (MACLE) (w/v), and 2% chitosan with 5% MECLE (w/v), respectively, to cast films. Of these, 2% chitosan (CH) with 5% MECLE (CH-MECLE-5) displayed the highest thickness and water vapor transmission rate, water vapor permeability, and oxygen transmission rate when compared to other film samples (p < 0.05). The CH-MECLE-5 film showed the highest inhibition zone of A. niger compared to the control and treated films (p < 0.05). The lightness (L*) of the CH-MECLE-5 film decreased with increment in b* values, which represented the yellow color of the film. In addition, two-photon microscopy revealed a uniform distribution via the auto-fluorescent 3D structure of MECLE in the CH-MECLE-5 film. Therefore, chitosan combined with 5% MECLE may be a potential bioactive and eco-friendly packaging film.


Parent and Physician Qualitative Perspectives on Reasons for Pediatric Hospital Readmissions.
One in 5 parents report a problem in their child's hospital-to-home transition, leading to adverse events, dissatisfaction, and readmissions. Although researchers in several studies have explored parent insights into discharge needs, few have explored perceptions of causes for pediatric readmissions. We sought to investigate factors contributing to pediatric readmissions, from both parent and physician perspectives. We conducted a qualitative study using semistructured interviews with parents, discharging and readmitting physicians, and subspecialist consultants of children readmitted within 30 days of initial discharge from the pediatric ward at an urban nonfreestanding children's hospital. Participants were interviewed during the readmission and asked about care transition experiences during the initial admission and potential causes and preventability of readmission. Data were analyzed iteratively by using a constant-comparative approach. We identified major themes, solicited feedback, and inferred relationships between themes to develop a conceptual model for preventing readmissions. We conducted 53 interviews from 20 patient readmissions, including 20 parents, 20 readmitting physicians, 11 discharging physicians, and 3 consulting subspecialists. Major themes included the following: (1) unclear roles cause lack of ownership in patient care tasks, (2) lack of collaborative communication leads to discordant understanding of care plans, and (3) incomplete hospital-to-home transitions result in ongoing reliance on the hospital. Clear definition of team member roles, improved communication among care team members and between care teams and families, and enhanced care coordination to facilitate the hospital-to-home transition were perceived as potential interventions that may help prevent readmissions.


Economic evaluation of upper limb prostheses in the Netherlands including the cost-effectiveness of multi-grip versus standard myoelectric hand prostheses.
To investigate the costs, quality of life, and user experiences associated with upper limb prosthesis use, and to evaluate the cost-effectiveness of multi-grip compared to standard myoelectric hand prostheses (MHPs/SHPs). The EQ-5D-5L to assess the quality of life, the patient-reported outcome measure to assess the preferred usage features of upper limb prosthesis (PUF-ULP), and a cost questionnaire (societal perspective) were completed by 242 prosthesis users (57% men; mean age = 58 years). Incremental cost-utility and cost-effectiveness ratios (ICUR/ICER) with respectively the EQ-5D-5L and PUF-ULP were calculated to compare MHPs with SHPs. Statistical uncertainty was estimated using bootstrapping. Netherlands Trial Registry number: NL7682. The mean yearly total costs related to prosthesis use of MHPs (€54 112) and SHPs (€23 501) were higher compared to prostheses with tools/accessories (€11 977), body-powered (€11 298), and cosmetic/passive prostheses (€10 132). EQ-5D-5L and PUF-ULP scores did not differ between prosthesis types. ICUR was €-728 833 per quality-adjusted life year; ICER was €-187 798 per PUF-ULP point gained. Myoelectric prostheses, especially MHPs, were most expensive compared to other prostheses, while no differences in quality of life and user experiences were apparent. MHPs were not cost-effective compared to SHPs. When prescribing MHPs, careful consideration of advantages over SHPs is recommended.


Conditional deletion of insulin-like growth factor-I receptor in prostate epithelium.
Insulin-like growth factor-I (IGF-I) is a polypeptide hormone that can influence growth, differentiation, and survival of cells expressing the cognate type 1 receptor (IGF-IR). To better understand cell autonomous IGF-IR signaling in the epithelial compartment of the prostate gland, we generated a conditional (Cre/loxP) prostate-specific IGF-IR knockout mouse model. In contrast to epidemiologic studies that established a correlation between elevated serum IGF-I and the risk of developing prostate cancer, we show that abrogation of IGF-IR expression in the dorsal and lateral prostate could activate extracellular signal-regulated kinase 1/2 signaling and cause cell autonomous proliferation and hyperplasia. Moreover, persistent loss of IGF-IR expression in dorsal and ventral lobes induced p53-regulated apoptosis and cellular senescence rescue programs, predicting that titration of IGF-IR signaling might facilitate growth of tumors with compromised p53 activity. Therefore, we crossed the mice carrying the prostate-specific IGF-IR knockout alleles into the transgenic adenocarcinoma of the mouse prostate model that is driven, in part, by T antigen-mediated functional inactivation of p53. Consistent with our prediction, prostate epithelial-specific deletion of IGF-IR accelerated the emergence of aggressive prostate cancer when p53 activity was compromised. Collectively, these data support a critical role for IGF-IR signaling in prostate tumorigenesis and identify an important IGF-IR-dependent growth control mechanism.


Defective neutrophil chemotaxis in bone marrow transplant patients.
Infection is a frequent cause of death in patients receiving bone marrow transplants. Although lymphocyte dysfunction has been observed in a few such patients, no systematic study of neutrophil function has yet been reported. Neutrophil chemotaxis was evaluated by a 51Cr-radioassay after bone marrow transplantation in 34 patients with acute leukemia or aplastic anemia. The response to a chemotactic stimulus (C5a) was severely depressed (less than 35% of normal) in 18 patients, moderately depressed (35-65% of normal) in an additional 6, and normal in 10 subjects. The mean response in the absence of graft vs. host disease and antithymocyte globulin administration was 73.3+/-9.2% (SE) in contrast to 29.7+/-9.6% (P is less than 0.01) in patients with graft vs. host disease treated with antithymocyte golbulin. Both graft vs. host disease and antithymocyte globulin were implicated since the presence of either factor alone was associated with depressed chemotaxis (31.1+/-4.9% for graft vs. host disease, P is less than 0.01; 17.0+/-7.8% for antithymocyte globulin, P is less than 0.02). When normal neutrophils were incubated with antithymocyte globulin in vitro, their chemotactic response was markedly suppressed in the absence of a cytotoxic effect. Transplant patients with defective chemotaxis experienced significantly more infections than those with normal chemotaxis, and analysis of specific etiologic agents showed that this was predominantly related to bacterial pathogens. Chemotactic inhibitors were detected in the sera of seven patients and elevated IgE levels were found in nine subjects, eight of whom had graft vs. host disease. Generation of chemotactic activity by endotoxin activation of serum was reduced in five patients. The results demonstrate a severe defect in neutrophil chemotaxis in some bone marrow transplant patients and suggest that neutrophil dysfunction may predispose to infection in such patients.


Similar uptake of lung carcinogens by smokers of regular, light, and ultralight cigarettes.
Cigarette design has changed markedly over the past 60 years and sales-weighed levels of tar and nicotine have decreased. Currently, cigarettes are classified as regular (>14.5 mg tar), light (>6.5-14.5 mg tar), and ultralight (< or =6.5 mg tar), based on a Federal Trade Commission-specified machine-smoking protocol. Epidemiologic studies suggest that there is no difference in lung cancer risk among people who smoke light or ultralight cigarettes compared with regular cigarettes, but the uptake of lung carcinogens in smokers of these types of cigarettes has never been reported. We recruited 175 smokers, who filled out a tobacco use questionnaire in which their current brand was identified as regular, light, or ultralight. Urine samples were collected and analyzed for 1-hydroxypyrene (1-HOP), total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL plus its glucuronides) and total cotinine (cotinine plus its glucuronides). 1-HOP and total NNAL are biomarkers of uptake of polycyclic aromatic hydrocarbons and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, lung carcinogens in cigarette smoke. Total cotinine is a biomarker of nicotine uptake. There were no statistically significant differences in urinary levels of 1-HOP, total NNAL, and total cotinine in smokers of regular, light, and ultralight cigarettes, whether the results were expressed per mg urinary creatinine, per mL of urine, or per mg creatinine divided by cigarettes per day. Levels of machine measured tar were available for the cigarettes smoked by 149 of the subjects. There was no correlation between levels of tar and any of the biomarkers. These results indicate that lung carcinogen and nicotine uptake, as measured by urinary 1-HOP, total NNAL, and total cotinine is the same in smokers of regular, light, and ultralight cigarettes. The results are consistent with epidemiologic studies that show no difference in lung cancer risk in smokers of these cigarettes.


Association between serum uric acid and cardiovascular mortality and all-cause mortality: a cohort study.
Previous studies have reported the association among serum uric acid (SUA) levels and cardiovascular and all-cause mortality; however, the results have been inconsistent. The aim of this study was to investigate whether SUA is independently associated with cardiovascular and all-cause mortality in relatively healthy Korean adults. A total of 396 951 individuals were enrolled for the study between 2002 and 2012. About 39 991 participants were excluded for various reasons. All-cause and cardiovascular mortality data were collected. Cox proportional hazards models were used to estimate adjusted hazard ratios and 95% confidence intervals for all-cause and cardiovascular mortality according to baseline uric acid quintiles, and the third, middle SUA quintile was the reference group. A total of 356 960 participants were considered to be eligible for the analysis, and median follow-up duration was 5.88 years. The lowest and highest quintiles of SUA were less than 5.2 and more than 7.1 mg/dl in men, and less than 3.5 and more than 5.0 mg/dl in women, respectively. A total of 2082 deaths (312 from cardiovascular disease and 1770 from other causes) occurred during follow-up. In the highest SUA group, adjusted hazard ratios for all-cause mortality were 1.24 (1.01, 1.51) in men and 1.04 (0.76, 1.42) in women, and for cardiovascular mortality were 1.15 (0.72, 1.83) in men and 1.69 (0.70, 4.04) in women after adjustment for various possible confounding factors. In the current large relatively healthy population-based observational study, SUA showed no significant association with all-cause and cardiovascular mortality.


Ultrathin LiCoO2 Nanosheets: An Efficient Water-Oxidation Catalyst.
Ultrathin cation-exchanged layered metal oxides are promising for many applications, while such substances are barely successfully synthesized to show several atomic layer thickness, owing to the strong electrostatic force between the adjacent layers. Herein, we took LiCoO2, a prototype cation-exchanged layered metal oxide, as an example to study. By developing a simple synthetic route, we synthesized LiCoO2 nanosheets with 5-6 cobalt oxide layers, which are the thinnest ever reported. Ultrathin nanosheets thus prepared showed a surprising coexistence of increased oxidation state of cobalt ions and oxygen vacancy, as demonstrated by magnetic susceptibility, X-ray photoelectron, electron paramagnetic resonance, and X-ray absorption fine spectra. This unique feature enables a higher electronic conduction and electrophilicity to the adsorbed oxygen than the bulk. Consequently ultrathin LiCoO2 nanosheets provided a current density of 10 mA cm-2 at a small overpotential of a mere 0.41 V and a small Tafel slope of ∼88 mV/decade, which is strikingly followed by an excellent cycle life. The findings reported in this work suggest that ultrathin cation-exchanged layered metal oxides could be a next generation of advanced catalysts for oxygen evolution reaction.


Role of cell membrane galactosyltransferase in concanavalin A agglutination of erythrocytes.
It has been previously observed that rabbit erythrocyte cell surface galactosyltransferase appears to play a role in concanavalin A agglutination of these erythrocytes (Podolsky et al., 1974). Further, a correlation between the occurrence or level of cell surface galactosyltransferase and concanavalin A agglutinability of other cell types has also been observed. The mechanism by which rabbit erythrocyte galactosyltransferase participates in concanavalin A agglutination has now been further defined. The enzyme was solubilized and purified. Characterization of the enzyme properties has shown them to be similar to those reported for other purified galactosyltransferases. Amino acid and carbohydrate analysis showed a high asparagine content and the presence of D-mannose. Specific alpha-mannosidase treatment of the enzyme showed that some of these D-mannose residues were terminal sugars. The purified enzyme also conferred concanavalin A agglutinability to non-agglutinable human erythrocytes. However, the ability to confer concanavalin A agglutinability was unrelated to the enzyme activity per se (as measured with fetuin acceptor) but appeared to be entirely dependent on the presence of terminal alpha-linked D-mannosyl residues in the enzyme structure. These findings suggest that the presence of terminal alpha-mannosidyl residues on cell surface glycoproteins such as galactosyltransferase may be the determining factor in agglutination of cells by concanavalin A.


Therapy of unstable angina with the low molecular weight heparins.
Unstable angina is in most cases caused by partial or complete coronary artery occlusion due to the disruption of an atherosclerotic plaque and to thrombus formation. An immediate antithrombotic approach is essential to prevent fatal and non-fatal myocardial infarction, and the combination of aspirin and unfractionated heparin has played a pivotal role in the past years. Low molecular weight heparins have improved pharmacokinetic and pharmacodynamic properties over unfractionated heparin that have resulted in greater efficacy and safety in the field of venous thromboembolism. Low molecular weight heparins can be administered by once or twice daily subcutaneous injections at fixed, weight-adjusted doses without the need for monitoring. Because of their potential, many recent clinical trials have evaluated their efficacy and safety in the management of patients with unstable angina. Three low molecular weight heparins have so far been tested: nadroparin, dalteparin and enoxaparin. The results of the published trials confirm that the newer compounds are at least as safe and effective as unfractionated heparin, and offer considerable therapeutic advantages. Nevertheless, the different properties of the three compounds and perhaps the different designs of the clinical trials have led to not entirely comparable findings.


Multilocus population genetics with weak epistasis. II. Equilibrium properties of multilocus models: what is the unit of selection?
Using perturbation techniques, I study the equilibrium of deterministic discrete time multilocus models with weak epistasis. The most important results are on the relationship between epistasis and disequilibrium. Disequilibrium involving a particular set of loci reflects only epistasis simultaneously involving those loci. Moreover, all the disequilibria of all orders vary approximately as the inverse of the probability of at least one recombination event among the loci involved. Finally, higher order disequilibria among loci will be lower than lower order ones, even if the level of epistasis is the same at all orders. In this sense, the unit of selection is small. However, given the larger number of higher order disequilibria, these higher order disequilibria may play an important role in the computation of gametic frequencies from allelic frequencies in models with a large number of loci. Finally, I show that epistasis between blocks of loci will be averages of epistatic effects, not additions of epistatic effects. Thus, failure to find significant epistasis on a chromosomal basis does not rule out the importance of epistatic effects.


[2-directional ventricular tachycardia associated with mitral valve prolapse].
We describe the case of a 11 year old male who developed a bidirectional tachycardia associated to mitral valve prolapse as the only evident anatomical anomaly. Simultaneous recordings of surface ECG readings and intracavitary tracings showed left ventricular origin of such tachycardia. In the present study we confirm the site of origin of the arrhythmia and the association between bidirectional tachycardia and mitral valve prolapse.


Risk Factors of Ectopic Pregnancy in Women Undergoing In Vitro Fertilization and Embryo Transfer (IVF-ET).
To identify risk factors associated with ectopic pregnancy (EP) in women undergoing assisted reproductive technology (ART). A retrospective study was conducted among pregnant women after in vitro fertilization and embryo transfer (IVF-ET) in an assisted conception unit of a university hospital between 1994 and 2013. The factors evaluated included the use of donor oocyte, use of intracytoplasmic sperm injection (ICSI), stage of embryo, number of embryos transferred, and fresh or frozen-thawed cycle. One thousand three hundred eighty five pregnancies were identified of which 29 were ectopic pregnancies. Embryo transfer (ET) in fresh cycle significantly increased risk for EP compared with frozen-thawed cycle (p = 0.005). Day-5 ET also significantly increased higher EP risk than day-3 ET (p = 0.041). Three or more embryos transfer (p = 0.085), use of donor oocyte (p = 0.999), and use of ICSI (p = 0.246) did not significantly influence EP risk. Embryo transfer in fresh cycle and day-5 embryo transfer significantly increased EP risk. More patients and embryo characteristics are necessary to be studied to identify more valid predictors.


Using clinicopathological analysis of general practitioner skin surgery to determine educational requirements and guidelines.
To study the impact of skin surgery in general practice on the workload of a pathology laboratory and to identify what further training might be helpful. Analysis of skin biopsy specimens from general practitioners before and after their new contract to determine numbers of specimens, changes in diagnoses, adequacy of treatment of malignant tumours, and areas of low diagnostic accuracy. District general hospital. All 1017 skin biopsy specimens from general practice for 15 months before and 12 months after the new general practitioner contract. The number of pathology specimens received increased from 16 to 65 per month (median = 6 submitted by each general practitioner in the post-contract year). The proportion of the more common pathological diagnoses was unchanged between the two periods, but the proportion of correctly diagnosed naevi, cysts, and seborrhoeic keratoses increased in the second. Although few diagnoses were overtly incorrect, accurate diagnosis of dermatofibromas and malignancies decreased after the contract, and the overall correct diagnosis rate for seborrhoeic keratoses, dermatofibromas, rashes, and malignancies was below 30%. Only nine out of 21 squamous cell carcinomas were adequately excised with tumour free margins, and follow up of malignant tumours may have been inadequate. Skin surgery in general practice has advantages but matters of concern are the increase in laboratory workload, the excision of some benign lesions, and the inappropriateness of biopsy of rashes. Squamous cell carcinoma and other malignant tumours submitted for pathological examination were often unsuspected and inadequately excised, and heightened suspicion is recommended. Pathology request forms may need redesigning to encourage provision of clinical details.


Radiation dose of the P-glycoprotein tracer 11C-laniquidar.
Resistance to current drug therapy is an important issue in the treatment of epilepsy. Inadequate access of central nervous system drugs to their targets in the brain may be caused by overexpression or overactivity of multidrug transporters, such as P-glycoprotein (P-gp), at the blood-brain barrier. Laniquidar, an inhibitor of P-gp, has been labeled with (11)C for use in PET studies of P-gp expression in humans. Given potential interspecies differences in biodistribution, the purpose of this study was to ensure safe use of (11)C-laniquidar by determining the dosimetry of (11)C-laniquidar using whole-body PET studies. Six healthy volunteers were subjected to a series of 10 whole-body PET scans within approximately 70 min. Five blood samples were taken during the series. High uptake of (11)C-laniquidar was seen in liver, spleen, kidneys, and lung, whereas brain uptake was low. The effective dose for (11)C-laniquidar was 4.76 ± 0.13 and 3.69 ± 0.01 μSv·MBq(-1) for women and men, respectively. Biodistribution and measured effective dose indicate that (11)C-laniquidar is a safe tracer for PET imaging, with a total dose of about 2 mSv for a brain PET/CT protocol.


Kneeling difficulty is common following anterior cruciate ligament reconstruction with hamstring autograft and correlates with outcome measures.
Patients frequently have discomfort or difficulty with kneeling following anterior cruciate ligament reconstruction (ACLR). This study aimed to report the prevalence of, and reasons for, kneeling difficulty after ACLR with a hamstring autograft; and to investigate the association between the degree of kneeling difficulty, presence of concurrent meniscal surgery, and clinical outcomes, including patient-reported outcome measures (PROMs) and functional tests. A total of 104 patients undergoing ACLR with ipsilateral hamstring autograft were enrolled. Participants completed a kneeling difficulty questionnaire and other PROMs including the International Knee Documentation Committee (IKDC) questionnaire, the Knee Injury and Osteoarthritis Outcome Score (KOOS), the Cincinnati Knee Rating System (CKRS), the Lysholm Knee Scoring Scale (LKS), the Tegner Activity Scale (TAS), the 36-Item Short Form Health Survey (SF-36), and the Knee Outcome Survey (KOS). Patients were also assessed objectively via peak isokinetic knee extensor and flexor strength, range of movement (ROM), and functional hop tests. The prevalence of kneeling difficulty on the operated knee was 77% and 54% at 1 and 2 years after ACLR, respectively. Strong associations were observed between kneeling difficulty and PROMs, ranging from CKRS at 1 year of r = 0.403 (95% CI 0.228-0.553, p < 0.001) to KOS at 2 years of r = 0.724 (95% CI 0.618, 0.804, p < 0.001). No associations were observed with age, body mass index, or knee ROM measures. Weak-to-moderate associations were demonstrated with functional hop tests. The degree of kneeling difficulty did not differ with concurrent meniscal surgery. Kneeling difficulty occurs in as much as 77% of patients following ACLR with hamstring grafts at 1 year, and 54% at 2 years. This has a moderate-to-very strong association with patient-reported assessment of knee pain, symptoms, sport and recreation, and knee-related quality of life. There appears to be no association with patient age, BMI, time from injury to surgery, knee ROM, or concurrent meniscal surgery. IV.


Potential Benefits of Acanthocephalan Parasites for Chub Hosts in Polluted Environments.
Some parasites are expected to have beneficial impacts on wild populations in polluted environments because of their bioaccumulation potential of pollutants from their hosts. The fate of organic micropollutants in host-parasite systems and the combined effect of parasitism and pollution were investigated in chub Squalius cephalus, a freshwater fish, infected (n = 73) or uninfected (n = 45) by acanthocephalan parasites Pomphorhynchus sp. from differently contaminated riverine sites. Several ubiquitous pollutants (polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), polybrominated diphenyl-ethers (PBDEs), polycyclic aromatic hydrocarbons (PAHs), phthalates, insecticides, pyrethroids, and N,N-diethyl-meta-toluamide (DEET)) and some of their metabolites were characterized for the first time in parasites and various fish matrices (muscle, liver, and stomach content). Most organic pollutants reached higher levels in parasites than in chub matrices. In contrast, metabolite levels were lower in parasite tissues compared to fish matrices. Infected and uninfected chub exhibited no significant differences in their pollutant load. Body condition, organo-somatic indices, and immunity were not affected by parasitism, and few correlations were found with chemical pollution. Interestingly, infected chub exhibited lower oxidative damage compared to uninfected fish, irrespective of their pollutant load. In light of these results, this correlative study supports the hypothesis that acanthocephalan parasites could bring benefits to their hosts to cope with organic pollution.


Essential Role for Zinc Transporter 2 (ZnT2)-mediated Zinc Transport in Mammary Gland Development and Function during Lactation.
The zinc transporter ZnT2 (SLC30A2) imports zinc into vesicles in secreting mammary epithelial cells (MECs) and is critical for zinc efflux into milk during lactation. Recent studies show that ZnT2 also imports zinc into mitochondria and is expressed in the non-lactating mammary gland and non-secreting MECs, highlighting the importance of ZnT2 in general mammary gland biology. In this study we used nulliparous and lactating ZnT2-null mice and characterized the consequences on mammary gland development, function during lactation, and milk composition. We found that ZnT2 was primarily expressed in MECs and to a limited extent in macrophages in the nulliparous mammary gland and loss of ZnT2 impaired mammary expansion during development. Secondly, we found that lactating ZnT2-null mice had substantial defects in mammary gland architecture and MEC function during secretion, including fewer, condensed and disorganized alveoli, impaired Stat5 activation, and unpolarized MECs. Loss of ZnT2 led to reduced milk volume and milk containing less protein, fat, and lactose compared with wild-type littermates, implicating ZnT2 in the regulation of mammary differentiation and optimal milk production during lactation. Together, these results demonstrate that ZnT2-mediated zinc transport is critical for mammary gland function, suggesting that defects in ZnT2 not only reduce milk zinc concentration but may compromise breast health and increase the risk for lactation insufficiency in lactating women.


Analyzing hematopoietic stem cell homing, lodgment, and engraftment to better understand the bone marrow niche.
The existence of a bone marrow (BM) niche--the location in which hematopoietic stem cells (HSCs) reside--was proposed more than 30 years ago. Recent data suggest that the interaction of HSCs with cellular and extracellular components within the BM is critical for HSC regulation. The tracking of immunofluorescently labeled, prospectively isolated HSCs to and within the BM cavity allows the assessment of the regulatory processes involved in (1) homing, which involves transendothelial migration into the BM; (2) lodgment, including transmarrow migration through the extravascular space; and (3) BM reconstitution. Together, such analyses provide a better understanding of the cellular and extracellular components involved in the regulation of HSC quiescence and differentiation. Homing and lodgment of transplanted HSCs, the first critical steps in engraftment, involve multiple interactions between HSCs and the BM microenvironment. Herein, we describe a refined method of analyzing homing efficiency and spatial distribution of HSCs harvested from endosteal and/or central BM regions; we also review alternate methods. Using these techniques, microenvironment modifications within the recipient or surface protein-expression modifications on donor HSCs in animal models provide insights into components influencing the homing, lodgment, and engraftment processes.


Anticancer activity of baicalein and luteolin studied in colorectal adenocarcinoma LoVo cells and in drug-resistant LoVo/Dx cells.
Due to the type-specific diversity of cancer cells, an analysis and elucidation of molecular mechanisms responsible for anticancer properties of biologically active compounds are essential. Plant-derived polyphenolic compounds such as flavonoids may be useful in cancer chemoprevention or treatment because they influence diverse molecular pathways in cancer cells. In these studies anticancer activity of natural occurring flavones, baicalein and luteolin was investigated in colon cancer cells LoVo and in their drug resistant subline LoVo/Dx. Inhibitory activity of these flavones on cells growth and their ability to induce apoptosis were observed. A less pronounced influence of studied flavones on proliferation and apoptosis of LoVo/Dx as compared with LoVo cells well correlated with significantly lower cytotoxicity of these compounds in drug-resistant cells. These effects may be related to overexpression of multidrug transporter P-glycoprotein in drug-resistant LoVo/Dx cells. Our studies indicated that baicalein could be a substrate of this drug transporter.


Frequency of ALK Rearrangement by FISH Testing and its Correlation with ALK-IHC in Adenocarcinoma of Primary Lung Origin
Anaplastic lymphoma kinase (ALK) gene can be oncogenic either by forming fusion with other genes, amplification of the gene or by having mutations. ALK rearrangement can either be detected by standard "fluorescence in situ hybridization (FISH)" or "immunohistochemistry (IHC)". Objective of this study was to record the prevalence of ALK rearrangement in adenocarcinoma of Primary Lung origin and compare it with ALK-IHC staining. Data of 64 patients of lung adenocarcinoma from 2015-2017 was analyzed. All of the FFPE biopsies were tested for EGFR (qPCR) followed by ALK rearrangement (by FISH and IHC) on EGFR negative samples. Out of 64 samples, 21.8% (14) showed EGFR mutations and 14% (7/50) were positive for ALK rearrangement when checked by FISH. In IHC testing for ALK (FISH positive) 8% (4/50) showed positivity. In conclusion ALK-FISH positive cases are higher than other studies likely due to the relatively small sample size. FISH testing was found to be more sensitive than IHC; one reason may be the low level of ALK. Our study warrants that currently FISH remains the gold standard for screening of ALK gene rearrangements.


Gap junction plasticity as a mechanism to regulate network-wide oscillations.
Cortical oscillations are thought to be involved in many cognitive functions and processes. Several mechanisms have been proposed to regulate oscillations. One prominent but understudied mechanism is gap junction coupling. Gap junctions are ubiquitous in cortex between GABAergic interneurons. Moreover, recent experiments indicate their strength can be modified in an activity-dependent manner, similar to chemical synapses. We hypothesized that activity-dependent gap junction plasticity acts as a mechanism to regulate oscillations in the cortex. We developed a computational model of gap junction plasticity in a recurrent cortical network based on recent experimental findings. We showed that gap junction plasticity can serve as a homeostatic mechanism for oscillations by maintaining a tight balance between two network states: asynchronous irregular activity and synchronized oscillations. This homeostatic mechanism allows for robust communication between neuronal assemblies through two different mechanisms: transient oscillations and frequency modulation. This implies a direct functional role for gap junction plasticity in information transmission in cortex.


Role of surface electrostatics in the operation of a high-conductance Ca2+-activated K+ channel.
This paper demonstrates that local electric fields originating from negatively charged groups on a K+-specific ion channel modify its behavior. Single high-conductance, Ca2+-activated K+ channels were studied in neutral phospholipid bilayers. The channel protein surface charges were manipulated experimentally by carboxyl group esterification using trimethyloxonium (TMO) or by electrolyte screening. Three channel properties--ion conduction, ion blockade, and voltage-dependent gating--are affected by surface electrostatics. Negative charges increase the affinity of cationic pore blockers by establishing a local negative potential at the pore entrance; these charges modify channel gating by establishing a potential gradient across the ion channel; finally, both effects influence ion permeation through the pore.


Mapping of independent V3 envelope determinants of human immunodeficiency virus type 1 macrophage tropism and syncytium formation in lymphocytes.
The V3 region of the human immunodeficiency virus type 1 (HIV-1) envelope protein is known to have a major influence on macrophage tropism as well as the ability to cause syncytium formation or fusion in CD4-positive lymphocyte cultures. Using infectious molecular HIV-1 clones, a series of mutant clones was created which allowed detailed mapping of V3 amino acid positions involved in these properties. In these experiments the non-syncytium-inducing phenotype in T cells did not always correlate with macrophage tropism. Macrophage tropism appeared to depend on the presence of certain combinations of amino acids at five specific positions within and just outside of the V3 loop itself, whereas syncytium formation in lymphocytes was influenced by substitution of particular residues at two to four positions within V3. In most cases, different V3 amino acid positions were found to independently influence macrophage tropism and syncytium formation in T cells and position 13 was the only V3 location which appeared to simultaneously influence both macrophage tropism and syncytium formation in lymphocytes.


Exacerbation of chronic inflammatory diseases by infectious agents: Fact or fiction?
Chronic inflammatory diseases caused by obesity represent critical public health concerns worldwide. In these diseases such as metabolic syndrome, diabetes and atherosclerosis, adipose tissue acts as an endocrine organ that releases large quantities of inflammatory mediators into circulation. Besides classically recognized effectors on the development of obesity and resultant conditions, infection has attracted attention as an enhancer of chronic inflammatory diseases. Infectious diseases have long been associated with obesity, metabolic syndrome, diabetes and atherosclerosis. However, the infectious hypothesis for chronic inflammatory diseases has been challenged by inconclusive clinical trials. Nevertheless, the large body of evidence accumulated over decades on the association of infectious diseases with obesity, diabetes and cardiovascular disease should not be disregarded. Instead, re-formulation of hypotheses of the mechanisms by which microbes affect obesity-associated diseases may be required with an emphasis on the early events in the progression of such diseases and the multifactorial nature of pathogen-host interactions. This review focuses on pathogens that directly promote obesity and on pathogens that cause chronic infections and thereby enhance metabolic diseases in obese patients. A new perspective on the interaction between infections and obesity-related diseases may improve management of chronic inflammatory diseases that rank high among global threats to human health.


Biomechanical evaluation of titanium, biodegradable plate and screw, and cyanoacrylate glue fixation systems in craniofacial surgery.
Choice of appropriate fixation after reduction of displaced bone fragments or advancement of osteotomized segments requires knowledge of the maximal force to which these segments can be subjected. The present study was performed to obtain a biomechanical comparison of a variety of resorbable fixation systems as an alternative to metal plates and screws. Sheep cadaver parietal bone segments were osteotomized and fixed with one of six methods of fixation: (A) titanium plates and screws consisting of (1) miniplates and 2.0-mm-diameter screws; (2) midface plates and 1.5-mm screws; (3) microplates and 1.0-mm screws; (B) resorbable systems consisting of combinations of butyl-2-cyanoacrylate glue and biodegradable polylactic acid/polyglycolic acid copolymer plates and 2.0-mm screws as follows: (1) direct glue fixation of segments; (2) resorbable plates fixed to bone segments with cyanoacrylate glue; (3) resorbable plates fixed with resorbable screws. Compression testing was performed upon bone segments advanced and fixed across a central gap, and distraction testing was performed on bone segments fixed in direct contact. Force to failure in both distraction and compression was significantly greater in bone segments fixed with titanium miniplates than with any other method of fixation. Segments fixed with plates and screws, either nonresorbable or resorbable, achieved stronger fixation in distraction than in compression for all plate sizes tested. Resorbable plate and screw fixation was as strong as standard titanium midface and microplating systems in distraction, and stronger than the latter techniques in compression. With compressive forces of relapse, fixation with glue and resorbable plates was as strong as standard titanium midface and microplating systems. However, with distractive forces of relapse, glue fixation of either the bone segments or resorbable plates was weaker than both titanium and resorbable alternatives in which plates and screws were used. These findings may have direct impact on the choice of fixation devices used to support osteotomized or fractured bone segments, which are subjected to persistent muscular and soft-tissue pull.


Buried penis release in adults with suction lipectomy and abdominoplasty.
The buried penis in adults who had substantial weight gain was treated with a combination of suction lipectomy of the abdomen and pubic area and the release of the suspensory ligament of the penis and with abdominoplasty with suture anchoring of the pubic and penile skin base dermis to the rectus fascia superiorly. This procedure was performed in 11 patients over the past 10 years with satisfactory results. One patient required additional excess skin excision from the side of the pubic and scrotal area to improve the results.


Growth Repressor GmRAV Binds to the GmGA3ox Promoter to Negatively Regulate Plant Height Development in Soybean.
Plant height is an important component of plant architecture, and significantly affects crop quality and yield. A soybean GmRAV (Related to ABI3/VP1) transcription factor containing both AP2 and B3 domains is a growth repressor. Three GmRAV-overexpressing (GmRAV-ox) transgenic lines displayed extremely shorter height and shortened internodes compared with control plants, whereas transgenic inhibition of GmRAV expression resulted in increased plant height. GmRAV-ox soybean plants showed a low active gibberellin level and the dwarf phenotype could be rescued by treatment with exogenous GA3 treatment. ChIP (Chromatin immunoprecipitation)-qPCR assay showed that GmRAV could directly regulate the expression of the GA4 biosynthetic genes GA3-oxidase (GmGA3ox) by binding two CAACA motifs in the GmGA3ox promoter. The GmGA3ox promoter was bound by GmRAV, whose expression levels in leaves were both elevated in GmRAV-i-3 and decreased in GmRAV-ox-7 soybean plants. Transient expression assay in N. benthamiana also showed that the proGmRAV:GmRAV-3F6H effector strongly repressed the expression of LUC reporter gene driven by GmGA3ox promoter containing two CAACA motifs. Together, our results suggested that GmRAV protein repressed the expression of GmGA3ox by directly binding to the two CAACA motifs in the promoter to limit soybean plant height.


Situation of Advertising Practices among Private Ayurveda Centers of Nepal - A Cross Sectional Study.
Advertisement plays a vital role in seeking health care services among the people. After the free market policy, advertising has been used by different private institutions for the promotion of their businesses. A descriptive cross-sectional study was done among the 40 private Ayurveda centers registered in the province registry of Nepal using convenience sampling. Semi-structured Interview and Key Informant interviews techniques were undertaken for quantitative and qualitative data collection. Data collected was edited, cleaned, and entered in MS-Excel, followed by analysis in the SPSS 22 version. Correlation between investment in advertisement and patient flow was found to be highly significant with a relation of 0.89 at 99% confidence level (p-value 0.01). Linear regression analysis shows 77.8 percent variability in the patient flow was explained by advertising. A one-unit increase advertisement investment was found to bring about 0.744 unit increase in patient flow. Unregulated advertising was done through Television, Radio, magazines, social media, and pamphlets. Free health camps conducted by the centers, and patient-to-patient referrals were found to be emerging ways. The phrases in ads like "100% cure" were replaced by the phrases such as "successful treatment" and "without operation treatment". This study shows unregulated, haphazard, and unethical advertising predominant among the private centres. There is a need for proper enforcement of the regulating act, formulation of proper guidelines about advertising, social media advertising, its content and censorship before broadcasting.


Dual effects of D-amphetamine on dopamine neurons mediated by dopamine and nondopamine receptors.
By increasing dopamine (DA) release and activating feedback mechanisms, amphetamine and related psychostimulants are known to inhibit DA cell firing. Here, we report that D-amphetamine also has an excitatory effect on DA cells, which under control conditions, is masked by the inhibitory effect of D-amphetamine and is revealed when D2-like receptors are blocked. Thus, using in vivo single-unit recording in rats, we found that the selective D2 antagonist raclopride not only blocked the inhibition induced by D-amphetamine but also enabled D-amphetamine to excite DA cells. The excitation, expressed as an increase in both firing rate and bursting, persisted when both D1- and D2-like receptors were blocked by SCH23390 and eticlopride, suggesting that it is not mediated by DA receptors. The norepinephrine uptake blocker nisoxetine mimicked the effect of D-amphetamine, especially the increase in bursting, whereas the 5-HT uptake blocker fluoxetine produced no significant effect. Adrenergic alpha1 antagonists prazosin and WB4101 and the nonselective alpha antagonist phenoxybenzamine completely blocked increase in bursting induced by D-amphetamine and partially blocked the increase in firing rate. The alpha2 antagonist idazoxan and the beta antagonist propranolole, however, failed to prevent D-amphetamine from producing the excitation. Thus, revising the traditional concept, this study suggests that D-amphetamine has two effects on DA cells, a DA-mediated inhibition and a non-DA-mediated excitation. The latter is mediated in part through adrenergic alpha1 receptors.


Salvianolic acid B protects SH-SY5Y neuroblastoma cells from 1-methyl-4-phenylpyridinium-induced apoptosis.
Parkinson's disease (PD) is associated with mitochondrial dysfunction, oxidative stress, and activation of the apoptotic cascade. In the study, we investigated the effects of salvianolic acid B (Sal B) on 1-methyl-4-phenylpyridinium (MPP(+))-treated SH-SY5Y cells, a classic in vitro model for PD. We found Sal B inhibited the loss of cell viability by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The underlying mechanisms of Sal B action were further studied. Treatment of SH-SY5Y cells with MPP(+) caused a loss of cell viability and mitochondrial membrane potential, condensation of nuclei, elevation in the level of reactive oxygen species (which was associated with cytochrome c release), an increase in the Bax/Bcl-2 mRNA ratio, and activation of caspase-3. Sal B ameliorated the MPP(+)-altered phenotypes. These results indicate that the Sal B protected SH-SY5Y cells against MPP(+)-induced apoptosis by relieving oxidative stress and modulating the apoptotic process. Our findings suggest that salvianolic acid B may be a promising agent to prevent PD.


[Method of determining proteolytic activity by using a conjugate of bovine serum albumin with peroxidase].
The authors propose a method for determination of proteolytic activity, based on the hydrolysis of peroxidase-labeled molecules of bovine serum albumin immobilized on the surface of polystyrene microassay plates with the subsequent determination of peroxidase activity on the carrier or in the solution. The optimum conditions for the sorption of the labeled substrate have been established. The method permits the determination of bacillary alkaline protease at a concentration of 01. microgram/ml within 45 minutes. The determination of four proteases has demonstrated that this method shows good correlation with the routine one (r = 0.98), but is more sensitive and less time- and labor-consuming.


A 17-kD centromere protein (CENP-A) copurifies with nucleosome core particles and with histones.
We have detected and begun to characterize a 17-kD centromere-specific protein, CENP-A (Earnshaw, W. C., and N. Rothfield, 1985, Chromosoma., 91:313-321). Sera from several humans with CREST scleroderma autoimmune disease (CREST: calcinosis, Raynaud's phenomenon, esophageal dsymotility, sclerodactyly, and telangiectasia) bind this protein in immunoblot assays of HeLa whole cell or nuclear extracts. We have affinity purified the anti-17-kD centromere protein (anti-CENP-A) specific antibodies from immunoblots of HeLa nuclear protein. The antibodies react with epitopes present on CENP-A derived from humans but apparently do not recognize specific epitopes in either rat or chicken nuclei. Only human nuclear protein is CENP-A positive by immunoblot. Furthermore, human cells show localization of anti-CENP-A antibody to centromeres by immunofluorescence microscopy, whereas rat cells do not. On extraction from the nucleus, CENP-A copurifies with core histones and with nucleosome core particles. We conclude that this centromere-specific protein is a histone-like component of chromatin. The data suggest that CENP-A functions as a centromere-specific core histone.


Contradictory mRNA and protein misexpression of EEF1A1 in ductal breast carcinoma due to cell cycle regulation and cellular stress.
Encoded by EEF1A1, the eukaryotic translation elongation factor eEF1α1 strongly promotes the heat shock response, which protects cancer cells from proteotoxic stress, following for instance oxidative stress, hypoxia or aneuploidy. Unexpectedly, therefore, we find that EEF1A1 mRNA levels are reduced in virtually all breast cancers, in particular in ductal carcinomas. Univariate and multivariate analyses indicate that EEF1A1 mRNA underexpression independently predicts poor patient prognosis for estrogen receptor-positive (ER+) cancers. EEF1A1 mRNA levels are lowest in the most invasive, lymph node-positive, advanced stage and postmenopausal tumors. In sharp contrast, immunohistochemistry on 100 ductal breast carcinomas revealed that at the protein level eEF1α1 is ubiquitously overexpressed, especially in ER+ , progesterone receptor-positive and lymph node-negative tumors. Explaining this paradox, we find that EEF1A1 mRNA levels in breast carcinomas are low due to EEF1A1 allelic copy number loss, found in 27% of tumors, and cell cycle-specific expression, because mRNA levels are high in G1 and low in proliferating cells. This also links estrogen-induced cell proliferation to clinical observations. In contrast, high eEF1α1 protein levels protect tumor cells from stress-induced cell death. These observations suggest that, by obviating EEF1A1 transcription, cancer cells can rapidly induce the heat shock response following proteotoxic stress, and survive.


N-linked high mannose-type oligosaccharides in the protozoa Crithidia fasciculata and Crithidia harmosa contain galactofuranose residues.
Incubation of Crithidia fasciculata cells with [U-14C] glucose led to the synthesis of Man-P-dolichol but not of Glc-P-dolichol. The main and largest dolichol-P-P-linked oligosaccharide formed was Man7GlcNAc2 whether labeling was performed in 5 mM sodium pyruvate or 5.5 mM glucose. The protein-linked, endo-beta-N-acetylglucosaminidase H-sensitive oligosaccharides isolated from mature glycoproteins were Man7GlcNAc and Gal1Man6GlcNAc, the latter being a mixture of two isomers. All the galactose residues were present in the furanose configuration, as judged by their extreme lability to acid hydrolysis, by the products obtained upon mild periodate oxidation, and by their sensitivity to beta-galactofuranosidase. Labeling cells for short times or at low temperature yielded a protein-bound, endo-beta-N-acetylglucosaminidase H-sensitive oligosaccharide whose composition was Glc1Man7GlcNAc, of transient existence, and that was mainly labeled in the glucose residue. The latter oligosaccharide was detected on paper chromatography only as a smearing of Man7GlcNAc and Gal1Man6GlcNAc when cells were labeled with [2-3H] mannose, thus indicating that it was only present in minute amounts. Protein-bound endo beta-N-acetylglucosaminidase H-resistant oligosaccharides liberated, upon a mild acid treatment, galactose residues and an unidentified substituent. The treatment rendered the oligosaccharides sensitive to endo beta-N-acetylglucosaminidase H, which liberated Man7GlcNAc and two isomers of Man6GlcNAc. An almost similar mechanism of protein N-glycosylation, including the existence of galactofuranose residues in N-linked oligosaccharides, was found to occur in Crithidia harmosa.


Diagnostic and prognostic significance of the IgM antibody to the hepatitis delta virus.
The IgM class antibody to the hepatitis delta virus (HDV) was determined in different clinical categories of hepatitis B surface antigen carriers infected by the HDV (positive in the test for total antibody to HDV). The IgM antibody was found at high titers in each of 70 patients with inflammatory liver disease and at a low titer in one of six patients with inactive cirrhosis; it was not found in eight carriers with normal liver histology. The IgM antibody persisted in high titer over many years in patients with unremitting or progressive liver disease, but declined or disappeared before the homologous IgG antibody in the patients whose disease improved or resolved. Testing for IgM antibody to HDV distinguishes hepatitis B surface antigen carriers who have underlying inflammatory HDV liver disease from those with past HDV infection and provides prognostic information on the course of chronic HDV hepatitis.


Correlation and prediction uncertainties in the cyberknife synchrony respiratory tracking system.
The CyberKnife uses an online prediction model to improve radiation delivery when treating lung tumors. This study evaluates the prediction model used by the CyberKnife radiation therapy system in terms of treatment margins about the gross tumor volume (GTV). From the data log files produced by the CyberKnife synchrony model, the uncertainty in radiation delivery can be calculated. Modeler points indicate the tracked position of the tumor and Predictor points predict the position about 115 ms in the future. The discrepancy between Predictor points and their corresponding Modeler points was analyzed for 100 treatment model data sets from 23 de-identified lung patients. The treatment margins were determined in each anatomic direction to cover an arbitrary volume of the GTV, derived from the Modeler points, when the radiation is targeted at the Predictor points. Each treatment model had about 30 min of motion data, of which about 10 min constituted treatment time; only these 10 min were used in the analysis. The frequencies of margin sizes were analyzed and truncated Gaussian normal functions were fit to each direction's distribution. The standard deviation of each Gaussian distribution was then used to describe the necessary margin expansions in each signed dimension in order to achieve the desired coverage. In this study, 95% modeler point coverage was compared to 99% modeler coverage. Two other error sources were investigated: the correlation error and the targeting error. These were added to the prediction error to give an aggregate error for the CyberKnife during treatment of lung tumors. Considering the magnitude of 2sigma from the mean of the Gaussian in each signed dimension, the margin expansions needed for 95% modeler point coverage were 1.2 mm in the lateral (LAT) direction and 1.7 mm in the anterior-posterior (AP) direction. For the superior-inferior (SI) direction, the fit was poor; but empirically, the expansions were 3.5 mm. For 99% modeler point coverage, the AP margin was 3.6 mm and the lateral margin was 2.9 mm. The SI margins for 99% modeler point coverage were highly variable. The aggregate error at 95% was 6.9 mm in the SI direction, 4.6 mm in the AP direction, and 3.5 in the lateral direction. The Predictor points follow the Modeler points closely. Margins were found in each clinical direction that would provide 95% modeler point coverage for 95% of the models reviewed in this study. Similar margins were found in two clinical directions for 99% modeler point coverage in 95% of models. These results can offer guidance in the selection of CTV margins for treatment with the CyberKnife.


Evaluation of the kinetic mechanism of Escherichia coli glycinamide ribonucleotide transformylase.
A kinetic scheme is presented for Escherichia coli glycinamide ribonucleotide transformylase (GAR transformylase, EC 126.96.36.199) based on a steady-state and pre-steady-state kinetic analysis of the reaction in both directions employing stopped-flow absorbance and fluorescence spectroscopy. Steady-state parameters showed that kcat for the reverse direction is about 10 times lower than that for the forward direction although the Km values for formyl dideazafolate and dideazafolate or for glycinamide ribonucleotide and formyl glycinamide ribonucleotide are similar. No pre-steady-state transient was observed in either direction, and the single-turnover rate constant under saturating levels of substrates in each direction was found to be very close to the respective steady-state kcat value. This indicates that steps involving ternary complexes are rate-determining for steady-state turnover in each direction. By conducting the single-turnover reactions under various preincubation and mixing conditions, a random sequential kinetic mechanism was implicated in which the enzyme binds glycinamide ribonucleotide or formyl dideazafolate productively in no obligatory order. The collective data provided a quantitative kinetic scheme to serve as a basis for the analysis of mutations.


Simple and rapid identification of the Mycobacterium tuberculosis complex by immunochromatographic assay using anti-MPB64 monoclonal antibodies.
A newly developed immunochromatographic assay (MPB64-ICA) for identification of the Mycobacterium tuberculosis complex was evaluated with 20 reference strains of mycobacterial species and 111 clinical isolates. MPB64-ICA displayed a very strong reaction band with organisms belonging to the M. tuberculosis complex but not with mycobacteria other than M. tuberculosis (MOTT bacilli), except for one of four M. marinum strains tested and one M. flavescens strain, both of which gave very weak signals. The effectiveness of MPB64-ICA in combination with two liquid culture systems (MB-REDOX and MGIT) was tested. A total of 108 of 362 sputum specimens processed were positive for acid-fast bacilli. Samples taken from the cultures on the same days when either of the two culture systems became positive for mycobacteria were assayed with MPB64-ICA. Of 108 cultures with mycobacteria, 51 showed a positive signal with the test, in which the presence of the M. tuberculosis complex was demonstrated later by the Accuprobe for M. tuberculosis complex. In addition, MPB64-ICA could correctly detect the M. tuberculosis complex in mixed cultures of the M. tuberculosis complex and MOTT bacilli. These results indicate that MPB64-ICA can be easily used for rapid identification of the M. tuberculosis complex in combination with culture systems based on liquid media without any technical complexity in clinical laboratories.


Four-quadrant optical matrix-vector multiplication machine as a neural-network processor.
Optical processors for neural networks are primarily fast matrix-vector multiplication machines that can potentially compete with serial computers owing to their parallelism and their ability to facilitate densely connected networks. However, in most proposed systems the multiplication supports only two quadrants and is thus unable to provide bipolar neuron outputs for increasing network capabilities and learning rate. We propose and demonstrate an opto-electronic four-quadrant matrix-vector multiplier that can be used for feed-forward neural-network recall and learning. Experimental results obtained with common commercial components demonstrate a novel, useful, and reliable approach for fourquadrant matrix-vector multiplication in general and for feed-forward neural-network training and recall in particular.


Interprofessionalism and shared decision-making in primary care: a stepwise approach towards a new model.
Most shared decision-making (SDM) models within healthcare have been limited to the patient-physician dyad. As a first step towards promoting an interprofessional approach to SDM in primary care, this article reports how an interprofessional and interdisciplinary group developed and achieved consensus on a new interprofessional SDM model. The key concepts within published reviews of SDM models and interprofessionalism were identified, analysed, and discussed by the group in order to reach consensus on the new interprofessional SDM (IP-SDM) model. The IP-SDM model comprises three levels: the individual (micro) level and two healthcare system (meso and macro) levels. At the individual level, the patient presents with a health condition that requires decision-making and follows a structured process to make an informed, value-based decision in concert with a team of healthcare professionals. The model acknowledges (at the meso level) the influence of individual team members' professional roles including the decision coach and organizational routines. At the macro level it acknowledges the influence of system level factors (i.e. health policies, professional organisations, and social context) on the meso and individual levels. Subsequently, the IP-SDM model will be validated with other stakeholders.


[Indications to balloon angioplasty and intracoronary stenting in patients with ischemic heart disease].
Four hundred and ten patients with ischemic heart disease (IHD) were treated. The study group consisted of 197 patients with IHD who have undergone intracoronary stenting (IS). The control group consisted of 213 patients treated with traditional balloon coronary angioplasty (BCA). All the patients in both groups were divided in four subgroups depending on a type of stenosis by classification ACC/AHA. A positive angiographic and clinical result straight away after IS was seen in all 197 patients. Any links with a stenosis type or with construction of the stent were not revealed. In 5 (2.5%) patients on day 5-7 after IS acute coronary occlusion in the place of stenting was seen. In 2 (1%) patients attempt of recanalization was unsuccessful, in both cases transmural myocardial infarction has developed. Thus, in further study 195 (98.98%) patients were included. Out of 213 patients after traditional BCA immediate good angiographic and clinical results were achieved in 191 (89.7%). There were no differences in rate of good immediate results of IS and BCA of types A and B1 stenoses. In types B2 and C stenosis immediate good results were achieved more often in group with IS. Good immediate results after BCA were better in patients with type A stenosis than with B2 and C stenoses. Rate of the "stent-like" result after BCA of types A and B1 stenosis was higher than after dilatation of types B2 and C stenosis. There was no difference in rate of restenosis after traditional BCA and IS of types A and B1 stenosis. In BCA of types B2 and C stenosis restenosis was seen more often than in IS. It is concluded that in patients with types A and B1 stenoses "stent-like" result is achieved more often after traditional BCA than in patients with types B2 and C stenosis. In patients with type A stenosis and "stent-like" result stenting does not improve significantly long-term results. In patients with types B2 and C stenosis and "stent-like" result IS is tustified. Good immediate results of angioplasty in these patients don't reduce the rate of restenosis, white IS does reduce its rate.


A Case of Healthcare Associated Pneumonia Caused by Chryseobacterium indologenes in an Immunocompetent Patient.
Chryseobacterium indologenes is nonmotile, oxidase, and indole positive Gram-negative aerobic bacilli which is widely found in plants, soil, foodstuffs, and water. It can colonize hospital environment due to ability to survive in chlorine-treated water supplies. Chryseobacteria can also colonize patients via contaminated medical devices such as respirators, intubation tubes, humidifiers, intravascular catheters, and prosthetic valves. Immune suppression, comorbidities, use of broad-spectrum antibiotics, and extreme age are other important risk factors for Chryseobacterium infections. We report a case of an 82-year-old male admitted to our hospital with the complaint of altered mental status with history of trauma, and recent orthopedic and neurosurgery operations. He was transferred to neurosurgery intensive care unit due to respiratory failure. Urine culture yielded extended spectrum beta lactamase (ESBL) (+). E. coli and C. indologenes were isolated from transtracheal aspirate. He was treated with ertapenem, and levofloxacin and discharged with full recovery.


Effect of time and storage conditions of Chemstrip bG on estimating blood glucose aboard ambulances.
This study tested the hypothesis that the age of Chemstrip bG aboard ambulances is not associated with decline of accuracy. This was accomplished by removing and testing Chemstrips bG from ambulances in Salt Lake City, Utah, U.S.A. Chemstrips were developed with three concentrations of glucose (2.0, 3.8, 12.4 mmol/L; 35, 68, 223 mg/dL, respectively) in a blinded manner by three different researchers and compared with fresh controls and with the Dimension Analyzer-derived glucose. Results showed that older Chemstrips read significantly higher than fresh strips at each value of glucose tested (p less than 0.05). Increased age was associated with higher readings. Therefore, it is possible that cases of hypoglycemia may be missed by reliance on older Chemstrips. While fresh strips tended to underestimate glucose at 12.4 mmol/L, age and storage aboard ambulances tended to reverse this underestimation; older Chemstrips were associated with a more accurate reading at 12.4 mmol/L. Older age was also associated with increased standard deviation of Chemstrips. Unless this bias is considered in clinical practice, it might result in a failure to detect and treat a patient with hypoglycemia. Chemstrips aboard ambulances should be interpreted with caution when evaluating a patient on the threshold of hypoglycemia. Meanwhile, institution of a quality control program is indicated. This would include periodic testing, but might also include storage of Chemstrips, when not in use, in a climate-controlled area either on or off the ambulance.