Effects of method on participants and disclosure rates in research on sensitive topics.
This study replicates and extends the research of Rosenbaum, Rabenhorst, Reddy, Fleming, and Howells, which also appears in this special issue. Responses from 398 randomly assigned participants regarding differentially sensitive topics were collected via four methods of data collection: written questionnaires, face-to-face interviews, telephone interviews, and an automated telephonic data collection system (ATDC). Several significant differences in data collection methodology and topic area were found, including greater disclosure of sensitive information via the ATDC system than via face-to-face and paper-and-pencil conditions. Participants who were assigned to the ATDC condition felt significantly more comfortable answering questions compared to those in the face-to-face interview condition. Participants in the telephone interview condition reported answering significantly more carefully than participants answering via written questionnaire. Taken together, the results of this study and the previous one it replicates suggest that the ATDC produces disclosure rates that are at least equivalent to, if not greater than, those generated using traditional methods for collecting sensitive data.


Application of Oxazaborolidine Catalysts (CBS) on Enantioselective 1,4-Addition of Diarylphosphine Oxides to α,β-Unsaturated Thioesters.
Here, we report the first catalytic enantioselective 1,4-addition of diarylphosphine oxides to α,β-unsaturated thioesters. Importantly, the most common and commercial oxazaborolidine (CBS) was employed as a catalyst for its new application without being activated by strong protonic acids or Lewis acids and led to the chiral thioesters in excellent yields and enantioselectivities. Furthermore, this method features mild reaction conditions (room temperature and air-insensitive), good substrate tolerance, and easy scalability.


Effect of laser photocoagulation, antiangiogenic therapy or a combined treatment on refractive outcomes of newborns with ROP.
To determine the refractive outcome after treatment with laser photocoagulation, intravitreal antiangiogenic injection or both, for the treatment of type 1 ROP and/or aggressive posterior ROP using defocus equivalent terms. These results will be compared with the spherical equivalent (SE) notation in an initial refraction (during the first 3 years after treatment) and in a final evaluation (three years after treatment). Clinical charts review of preterm patients who developed type 1 ROP and/or aggressive posterior ROP who were treated with laser photocoagulation, intravitreal antiangiogenic injection, or both, between January 2007 and December 2014 at Fundación Oftalmológica de Santander were reviewed. Refractive error was evaluated at two different time points in three different treatment groups. Seventy-seven eyes (56 patients) with ROP diagnosis treated with laser, antiangiogenics or in a combined scheme were included. Median gestational age was 29 weeks (IQR = 3), median birth weight was 1100 (IQR = 335) and mean corrected age at the time of treatment was 37.3 weeks (SD 2.2). Refractive outcomes in SE terms for the first refraction had a median of -0.50 diopters and in defocus terms, 4.00 diopters (D). For the second refraction, -3.00 diopters and 4.00 diopters (D), respectively. Pearson correlation test result for the first measurement was 93% (p = 0.000) and for the second evaluation was 99% (p = 0.000). Low birth weight had a statistically significant association to the increase of the refractive outcome. The high correlation between SE and DE for refractive errors allows us to confirm that DE is an appropriate metric to report refractive outcomes in this group of patients due to the presence of combined refractive ametropias.


Ecological constraints influence the emergence of cooperative breeding when population dynamics determine the fitness of helpers.
Cooperative breeding is a system in which certain individuals facilitate the production of offspring by others. The ecological constraints hypothesis states that ecological conditions deter individuals from breeding independently, and so individuals breed cooperatively to make the best of a bad situation. Current theoretical support for the ecological constraints hypothesis is lacking. We formulate a mathematical model that emphasizes the underlying ecology of cooperative breeders. Our goal is to derive theoretical support for the ecological constraints hypothesis using an ecological model of population dynamics. We consider a population composed of two kinds of individuals, nonbreeders (auxiliaries) and breeders. We suppose that help provided by an auxiliary increases breeder fecundity, but reduces the probability with which the auxiliary becomes a breeder. Our main result is a condition that guarantees success of auxiliary help. We predict that increasing the cost of dispersal promotes helping, in agreement with verbal theory. We also predict that increasing breeder mortality can either hinder helping (at high population densities), or promote it (at low population densities). We conclude that ecological constraints can exert influence over the evolution of auxiliary help when population dynamics are considered; moreover, that influence need not coincide with direct fitness benefits as previously found.


Blunt and penetrating object injuries in housekeepers working in a Turkish University Hospital.
Hospitals have been described as hazardous work environments with an increase in job-related injuries. This situation creates great risks and hazards for housekeepers while carrying out their job. This descriptive study was performed on 402 housekeepers working in patient-care services in Turkey. The data of this study were collected using a questionnaire form. This form included 26 questions about general features of housekeepers and working units, blunt and penetrating object injuries in the past 3 months and hepatitis B virus immunization. The majority of housekeepers (71.1%) are men, (54%) are graduates of primary school or are illiterate, and (73.6%) are married. Their mean age is 31.5 years; the mean length of employment is 3.2 years. Sixty-two point nine percent of them are working in medical/surgical units, 88.8% of them are working in routine cleaning, and 29.1% of them have been injured with various blunt and penetrating objects while working in hospital in the past 3 months. Only 26.6% of the housekeepers have been administered the hepatitis B vaccination. This study showed a high frequency of blunt and penetrating object injuries in housekeepers. Therefore, more efforts are necessary to increase compliance with vaccination in housekeepers.


Aldosterone and nuclear signaling in kidney.
Initiation of transcription is an early step in steroid hormone action. We investigated by means of atomic force microscopy (AFM) and fluorescence imaging the role of nuclear pore complexes (NPCs) in mediating signal transduction of the mineralocorticoid hormone aldosterone from the extracellular space into the cell nucleus. With AFM, we imaged single NPCs of isolated nuclear envelopes under native conditions. We observed that individual NPCs contract in response to a Ca2+ signal, which is known to occur in seconds after aldosterone exposure. In living kidney cells in culture (MDCK cells), aldosterone led within seconds to the contraction of the whole nucleus measured by DNA-fluorescence imaging. Nuclear contraction was elicited at similar time scale and to similar extent by bradykinin, a peptide hormone known to mobilize Ca2+ from internal stores, and by ionomycin, a Ca2+ ionophore known to directly increase intracellular Ca2+. Nuclear contraction is explained by the individual contraction of calcium-sensitive NPCs that occur in high density in the nuclear envelope. We present a model in which nuclear pore complexes play a key role as barrier molecules of high plasticity in the control of aldosterone-induced gene expression.


Interaction stabilizing tertiary structure of bacteriorhodopsin studied by denaturation experiments.
The structural stability of bacteriorhodopsin was studied by denaturation experiments, using aliphatic alcohol as denaturants. The disappearance of a positive peak at 285 nm of the circular dichroism spectra, the change in the intrinsic fluorescence decay time, and the decrease of the regeneration activity bacteriorhodopsin indicated the denaturation of the tertiary structure of this protein at a methanol concentration of about 3 M. The circular dichroism band at 222 nm was unchanged by the denaturation. It was concluded that the alcohol-denatured state in water was similar to the molten globule state of soluble proteins, in which only the tertiary structure was destroyed. Solvent substitution from water to hexane did not cause denaturation of bacteriorhodopsin. However, further addition of alcohol destroyed the secondary as well as the tertiary structures. Comparing the alcohol effects of bacteriorhodopsin in water to that in hexane, the dominant interactions for the structure formation of this protein could be revealed: the hydrophobic interaction that arose from the structure of water is essential for the stability of membrane spanning helices, while the interaction which binds the helices is polar in nature.


Frequent c-fms activation by proviral insertion in mouse myeloblastic leukaemias.
Retroviruses lacking oncogenes can induce tumours in animals, and the tumour cells are frequently found to contain proviral DNA inserted next to a proto-oncogene, which is thus placed under the regulatory control of the retroviral long terminal repeat (LTR). This altered regulation leads to overexpression of the proto-oncogene, which presumably contributes to the growth properties of the tumour cells. fim-2 has been described as a retroviral integration site frequently and specifically involved in murine myeloblastic leukaemias induced in vivo or in vitro by the replication-competent Friend murine leukaemia virus (F-MuLV). Here we report that fim-2 spans the 5'-end of the murine proto-oncogene c-fms, known to code for a transmembrane glycoprotein with tyrosine kinase activity probably identical to the receptor of the haemopoietic growth factor, monocyte-macrophage colony-stimulating factor (M-CSF or CSF-1). Proviral integration in the fim-2 region results in a high expression of a normal sized c-fms messenger RNA. We also observe that some tumours have lost the fim-2/c-fms germ line allele. These results provide the first evidence for the presumed involvement of c-fms in myelomonocytic leukaemias.


Alpha interferon suppresses virion but not soluble human immunodeficiency virus antigen production in chronically infected T-lymphocytic cells.
Alpha interferon (IFN-alpha) is effective in preventing the release of human immunodeficiency virus (HIV) from chronically infected T-lymphocytic (ACH-2) and promonocytic (U1) cell lines stimulated with the phorbol ester phorbol-12-myristate-13 acetate (PMA). In the present study, we observed that together with particle production, shedding of HIV antigen (p24gag) occurs in the T-cell line ACH-2 both constitutively and after stimulation with PMA. IFN-alpha, although effective in suppressing the release of HIV particles, did not inhibit shedding of p24gag into the culture supernatants of either unstimulated or PMA-stimulated cells. These observations may be of relevance in the evaluation of the in vivo efficacy of IFN-alpha treatment of HIV-infected individuals as determined by levels of p24 antigen in plasma.


The dynamics of CO production from the photolysis of acetone across the whole S1 ← S0 absorption spectrum: Roaming and triple fragmentation pathways.
The unimolecular photodissociation dynamics of acetone spanning the entire S1 ← S0 absorption spectrum have been reinvestigated, with a focus on mechanisms that produce CO. At excitation wavelengths of λ > 305.8 nm, all photoproducts are formed on the S0 state after internal conversion. A roaming mechanism forming C2H6 + CO is active in the window λ = 311.2-305.8 nm. From λ = 305.8 to 262 nm, little or no CO is produced with the photochemistry dominated by the Norrish-type I C-C bond cleavage on the lowest excited triplet state, T1. At higher energy (λ < 262 nm), an increasing fraction of CH3CO radicals from the primary reaction have sufficient internal energy to spontaneously decompose to CH3 + CO. A new model is presented to account for the kinetic energy distribution of the secondary CH3 radical, allowing us to determine the height of the energetic barrier to CH3CO decomposition as 68 ± 4 kJ mol-1, which lies midway between previous measurements. The fraction of CO from triple fragmentation rises smoothly from 260 to 248 nm. We see no evidence of the return of roaming, or any other S0 reaction, in this higher energy region of the first electronic absorption band.


Role of normal serum in the binding of lipopolysaccharide to IgG fractions from rabbit antisera to Escherichia coli J5 and other gram-negative bacteria.
Because lipopolysaccharide (LPS) bound to lipoprotein is less active than unbound LPS in multiple assay systems, the binding of radiolabeled LPS to lipoproteins in sera prepared from normal rabbits and rabbits made hyperimmune to Escherichia coli J5 were compared. LPS-lipoprotein binding in hyperimmune sera to E. coli J5 was not greater than that in normal serum as assessed by ultracentrifugation, but more LPS was precipitated from hyperimmune antisera than normal sera under conditions designed to precipitate LPS-lipoprotein complexes with calcium and dextran. Radiolabeled LPS was precipitated by delipidated antisera and fractions of IgG purified by anion exchange chromatography, but the precipitation was dependent on the presence of normal serum in the reaction mixture. These data suggest that a fluid-phase RIA done in the presence of normal serum may facilitate the detection of IgG in antisera raised to E. coli J5 that binds to heterologous smooth LPS.


Temperature drives caste-specific morphological clines in ants.
The morphology of organisms relates to most aspects of their life history and autecology. As such, elucidating the drivers of morphological variation along environmental gradients might give insight into processes limiting species distributions. In eusocial organisms, the concept of morphology is more complex than in solitary organisms. Eusocial insects such as ants exhibit drastic morphological differences between reproductive and worker castes. How environmental selection operates on the morphology of each caste, and whether caste-specific selection has fitness consequences is largely unknown, but is potentially crucial to understand what limits ant species' distributions. Here we aimed to examine whether ant shape and body size covaries with climate at the scale of an entire continent, and whether such relationship might be caste specific. We used 26,472 georeferenced morphometric measurements from 2,206 individual ants belonging to 32 closely related North American species in the genus Formica to assess how ant morphology relates to geographic variation in the abiotic environment. Although precipitation and seasonality explained some of the geographic variation in morphology, temperature was the best predictor. Specifically, geographic variation in body size was positively related to temperature, meaning that ants are smaller in cold than in warm environments. Moreover, the strength of the relationship between size and temperature was stronger for the reproductive castes (i.e. queens and males) than for the worker caste. The shape of workers and males also varied along these large-scale abiotic gradients. Specifically, the relative length of workers' legs, thoraxes and antennae positively related to temperature, meaning that they had shorter appendages in cold environments. In contrast, males had smaller heads, but larger thoraxes in more seasonal environments. Overall, our results suggest that geographic variation in ambient temperature influences the morphology of ants, but that the strength of this effect is caste specific. In conclusion, whereas ant ecology has traditionally focused on workers, our study shows that considering the ecology of the reproductive castes is imperative to move forward in this field.


[Development of monitoring of population health, environment and public health at a regional level].
A structural model of monitoring, intending the creation of a multifunctional multi-level information system, is suggested for creation of a universal information analytical data bank on population health, human environment, and public health activities at a regional level.


Identifying disease foci from static and dynamic effective connectivity networks: Illustration in soldiers with trauma.
Brain connectivity studies report group differences in pairwise connection strengths. While informative, such results are difficult to interpret since our understanding of the brain relies on region-based properties, rather than on connection information. Given that large disruptions in the brain are often caused by a few pivotal sources, we propose a novel framework to identify the sources of functional disruption from effective connectivity networks. Our approach integrates static and time-varying effective connectivity modeling in a probabilistic framework, to identify aberrant foci and the corresponding aberrant connectomics network. Using resting-state fMRI, we illustrate the utility of this novel approach in U.S. Army soldiers (N = 87) with posttraumatic stress disorder (PTSD), mild traumatic brain injury (mTBI) and combat controls. Additionally, we employed machine-learning classification to identify those significant connectivity features that possessed high predictive ability. We identified three disrupted foci (middle frontal gyrus [MFG], insula, hippocampus), and an aberrant prefrontal-subcortical-parietal network of information flow. We found the MFG to be the pivotal focus of network disruption, with aberrant strength and temporal-variability of effective connectivity to the insula, amygdala and hippocampus. These connectivities also possessed high predictive ability (giving a classification accuracy of 81%); and they exhibited significant associations with symptom severity and neurocognitive functioning. In summary, dysregulation originating in the MFG caused elevated and temporally less-variable connectivity in subcortical regions, followed by a similar effect on parietal memory-related regions. This mechanism likely contributes to the reduced control over traumatic memories leading to re-experiencing, hyperarousal and flashbacks observed in soldiers with PTSD and mTBI. Hum Brain Mapp 39:264-287, 2018. © 2017 Wiley Periodicals, Inc.


The role of anterior segment optical coherence tomography in uveitis-glaucoma-hyphema syndrome.
To describe features of uveitis-glaucoma-hyphema (UGH) syndrome, using Anterior Segment-Optical Coherence Tomography (AS-OCT) and Ultrasound Biomicroscopy (UBM) and to evaluate the diagnostic role of AS-OCT as an imaging technique alternative to UBM. Retrospective case series. Four eyes of 4 patients with UGH syndrome were analyzed. All patients reported previous uncomplicated cataract surgery with in-the-bag implantation of single-piece-intraocular lens (IOL). They underwent at presentation complete ophthalmological examination and imaging with slit-lamp anterior segment photographs, UBM and AS-OCT. Although AS-OCT did not allow to visualize the structures behind the iris, it displayed a contact between IOL (plate and/or haptics) and iris and IOL tilting in 3 out of 4 eyes. AS-OCT directly detected the cause of UGH syndrome in one eye, 2 eyes required some expedients to display the iris chafing, like scans in mydriasis and/or patient's gaze direction change. AS-OCT did not allow to appreciate the IOL-iris contact (showed by UBM technique) only in one eye, probably due to the change of patient position from supine to sitting, and consequent anteriorization of iris diaphragm. Furthermore AS-OCT showed fine details, as capsular bag collapse and indirect signs of haptic malposition in 3 out of 4 eyes. AS-OCT is a non-invasive technique that allows to determine IOL position and IOL-uveal contact in selected cases of UGH syndrome. Considering AS-OCT and UBM advantages and limitations, AS-OCT should be used as first imaging modality when clinical diagnosis is uncertain. When UGH diagnosis cannot be verified using AS-OCT, UBM should be performed.


Molecular and Genetic Predictors of Breast-to-Brain Metastasis: Review and Case Presentation.
Brain metastases are the most common intracranial malignancy, and breast cancer is the second most common cancer to metastasize to the brain. Intracranial disease is a late manifestation of breast cancer with few effective treatment options, affecting 15-50% of breast cancer patients, depending upon molecular subtype. In this review article, we describe the genetic, molecular, and metabolic changes in breast cancer cells that facilitate breast to brain metastasis. We believe that advances in the understanding of breast to brain metastasis pathogenesis will lead to targeted molecular therapies and to improvements in the ability to prospectively identify patients at increased risk for developing intracranial disease.


Neuroreceptors and ion channels as targets of alcohol.
This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Toshio Narahashi and Kinya Kuriyama. The presentations were (1) Modulation of neuroreceptors and ion channels by alcohol, by T. Narahashi; (2) Inhibition by ethanol of NMDA and AMPA receptor-channels, by P. Illes, K. Wirkner, W. Fischer, K. Mühlberg, P. Scheibler, and C. Allgaier; (3) Effects of ethanol on metabotropic glutamate receptors, by K. Minami; (4) Acute alcohol actions on the 5-HT3 ligand-gated ion channel, by D. Lovinger; (5) Inhibition of NMDA receptors by MK801 attenuates ethanol-induced taurine release from the hippocampus, by F. Lallemand, R.J. Ward, and P. DeWitte; and (6) Effect of ethanol on voltage-operated Ca2+ channels in hepatic stellate cells, by T. Itatsu, Y. Takei, H. Oide, M. Hirose, X. E. Wang, S. Watanabe, M. Tateyama, R. Ochi, and N. Sato.


[Focal glomerular sclerosis in a sibling].
We described here one sibling with focal glomerular sclerosis. Proteinuria was noticed at the age of five in brother and four in sister. Both of them developed nephrotic syndrome shortly after the discovery of proteinuria. The nephrotic syndrome was resistant to corticosteroid, immunosuppressive agents or the combination of these drugs. Percutaneous renal biopsy in them revealed morphological and immunohistological features compatible to focal glomerular sclerosis. HLA typing in HLA-A, B, C and DR loci was identical to both. This observation suggests that genetic factors is associated with the pathogenesis of focal glomerular sclerosis.


Performance Analysis of Public Safety Cognitive Radio MANET for Diversified Traffic.
This paper presents properties of a mobile ad hoc network (MANET) with dynamic spectrum management (DSM) and is devoted to the concept and implementation of the new traffic engine that is used in a High-Fidelity simulator of MANET with cognitive nodes for special applications. The communication traffic generated by each node is defined according to its role in the hierarchical structure of the operational scenario, determining its priorities, permission to use particular real time and non-real time services. The service usage is a source based model, defined in the user's profile containing its statistical properties, describing periodicity, duration and randomness of traffic generation. The overall traffic generated by the node is a combination of traffics related to specific services. Their statistical parameters are based on real exercises results. The model was defined in the Matlab environment and next verified using the MAENA simulator for complex, operational scenarios. The achieved results show that use of both central and distributed DSM provides a better performance of the MANET network with complex traffic.


Sea level as affected by river runoff, eastern United States.
Variations in annual river inflow account for 7 to 21 percent of the total variation in average annual sea level along the Atlantic and Gulf of Mexico coasts of the United States. This compares with 29 to 68 percent of the total variation that can be attributed to the secular rise of sea level, and with 10 to 50 percent of the variation that cannot be attributed to either the river inflow or the secular rise.


X-ray diffraction analysis of cytochrome P450 2B4 reconstituted into liposomes.
Two general models of the membrane topology of microsomal cytochrome P450 have been proposed: (1) deep immersion in the membrane, and (2) a P450cam-like heme domain anchored to the membrane with one or two membrane-spanning helices. Lamellar X-ray diffraction of oriented membrane multilayers was employed to distinguish these alternatives. Cytochrome P450 2B4 was reconstituted into unilamellar phospholipid proteoliposomes (molar protein to lipid ratio 1:90). Sedimentation of the proteoliposomes produced an ordered stack of bilayers with a one-dimensional repeat distance (d) perpendicular to the plane of the bilayer. The stacked multilayers were exposed to an X-ray beam (lambda = 1.54 A) at near grazing incidence, and lamellar diffraction patterns were recorded. With proteoliposome multilayers, up to six diffraction orders could be observed. Their spacing corresponded to a d of 63.6 A, calculated according to Bragg's Law, comprising the lipid bilayer, the projection of the incorporated protein beyond the bilayer, and the intermembrane water layer. With liposome multilayers containing no P450, the observed d was 59.6 A. These data suggest that the increase of distance between successive bilayers in the stack due to the presence of P450 2B4 was only about 4 A. This distance is much less than would be expected with the "N-terminal membrane-anchor" model of the membrane topology, in which the P450 molecules largely extend beyond the surface of the membrane (> or = 35 A). Furthermore, the mass distribution deduced from Fourier synthesis confirms that the protein is deeply immersed in the membrane.


Increasing Prevalence of Nephrolithiasis in Association with Increased Body Mass Index in Children: A Population Based Study.
Epidemiological studies demonstrate an association of increased body mass index and risk of kidney stone formation in adults. We conducted a population based pediatric study to examine the epidemiology of nephrolithiasis in Israeli children during a 30-year period, and to determine body mass index distribution during the same period. We accessed data from the compulsory medical evaluations of 17-year-old military service candidates in Israel before their enlistment during 1980 to 2013. Candidates for the army with a history of stone disease were compared to those without such a history. Of 1,908,893 candidates 1,691 reported a history of nephrolithiasis, yielding an average prevalence rate of 88.6 per 100,000. During 1980 to 1995 the average reported prevalence of nephrolithiasis was 69 cases per 100,000. From 1995 onward the reported prevalence increased by an average of 6% yearly, reaching 120 per 100,000 during 2010 to 2012. This increased prevalence was observed for males and females but was more prominent among males. Mean ± SD body mass index of stone formers was higher than that of controls (22.7 ± 3.5 vs 22.1 ± 3.9 kg/m2, p <0.001). The trend of increasing body mass index among male candidates during 1995 to 2012 parallels the trend of increasing nephrolithiasis during these years. The odds ratio for nephrolithiasis in candidates with body mass index 30 or greater kg/m2 was 1.7 (range 1.4 to 2.1) compared to candidates with a body mass index of 18.5 to 24.9 kg/m2. This large, population based study documents an increasing prevalence of nephrolithiasis in children. The possible association of this finding with the increase in body mass index during the same period warrants further investigation.


Water-in-Oil Pickering Emulsions Stabilized by Synergistic Particle-Particle Interactions.
Here, we report a novel "double Pickering stabilization" of water-in-oil (W/O) emulsions, where complex formation at the interface between Pickering polyphenol particles adsorbing from the oil side and whey protein microgel (WPM) particles coadsorbing from the aqueous side of the interface is investigated. The interfacial complex formation was strongly dependent on the concentration of WPM particles. At low WPM concentrations, both polyphenol crystals and WPM particles are present at the interface and the water droplets were stabilized through their synergistic action, while at higher concentrations, the WPM particles acted as "colloidal glue" between the water droplets and polyphenol crystals, enhancing the water droplet stability for more than 90 days and prevented coalescence. Via this mechanism, the addition of WPM up to 1 wt % gave a significant improvement in the stability of the W/O emulsions, allowing an increase to a 20 wt % water droplet fraction. The evidence suggests that the complex was probably formed due to electrostatic attraction between oppositely charged polyphenol Pickering particles on the oil side of the interface and WPM Pickering particles mainly on the aqueous side of the interface. Interfacial shear viscosity measurements and monolayer (Langmuir trough) experiments at the air-water interface provided further evidence of this strengthening of the film due to the synergistic particle-particle complex formation at the interface.


Transplasma membrane electron transport in Leishmania donovani promastigotes.
Leishmania donovani promastigotes are capable of reducing certain electron acceptors with redox potential at pH 7 down to -125 mV; outside the plasma membrane promastigotes can reduce ferricyanide. Ferricyanide has been used as an artificial electron acceptor probe for studying the mechanism of transplasma membrane electron transport. Transmembrane ferricyanide reduction by L. donovani promastigotes was not inhibited by such mitochondrial inhibitors as antimycin A or cyanide, but it responded to inhibitors of glycolysis. Transmembrane ferricyanide reduction by Leishmania appears to involve a plasma membrane electron transport chain dissimilar to that of hepatocyte cells. As with other cells, transmembrane electron transport is associated with proton release, which may be involved in internal pH regulation. The Leishmania transmembrane redox system differs from that of mammalian cells in being 4-fold less sensitive to chloroquine and 12-fold more sensitive to niclosamide. Sensitivities to these drugs suggest that transplasma membrane electron transport and associated proton pumping may be targets for the drugs used against leishmaniasis.


Factors Associated with Symptoms of Depression among Injection Drug Users Receiving Antiretroviral Treatment in Indonesia.
Few studies have examined psychiatric comorbidity among HIV positive injection drug users (IDUs) in resource-limiting settings. We sought to identify key factors associated with symptoms of depression among IDUs receiving antiretroviral (ARV) treatment in Jakarta and Denpasar, Indonesia. The cross-sectional study was conducted at five ARV delivery sites in Indonesia. Former IDUs aged 18 years or older having received ARV treatment for at least three months (n=117) were recruited and interviewed face-to-face. A 9-item version of the Center for Epidemiologic Studies Depression Scale was used to measure symptoms of depression. A structured questionnaire measured participants' demographic characteristics, social support and services received, current substance use, and treatment for drug dependency and HIV. Multiple logistic regression was used to calculate adjusted odds ratios (AOR) and 95% confidence intervals (CI). Of the 117 participants, 33% (39) exhibited symptoms of depression, 24% (28) reported using an illicit substance in the past month, and 29% (34) were in methadone treatment. Depressive symptoms were significantly associated with recent substance use in the last 30 days (AOR, 95% CI: 5.3, 1.9 to 15.4) and being on methadone (3.5, 1.2 to 10). Older age (per year 0.9, 0.8 to 1), full-time employment (0.2, 0.1 to 0.7), and living with parents (0.2, 0.1 to 0.6) appeared to be protective. The results suggest that depression is common among Indonesian IDUs, even among patients enrolled in methadone treatment. HIV clinics and drug treatment programs need to recognize the risk/protective factors and also provide services to address this common comorbidity.


Determinants of accrual of women to a large, multicenter clinical trials program of human immunodeficiency virus infection. The AIDS Clinical Trials Group.
To determine factors influencing the enrollment of women in a large multicenter human immunodeficiency virus (HIV) clinical trials program in the United States, we analyzed enrollment and demographic data of the AIDS Clinical Trials Group (ACTG) during the period 1987-90. Women comprised 6.7% of 11,909 ACTG participants enrolled in 1987-90. Women entering ACTG trials were significantly more likely to be white (48.5%) and less likely to have ever used i.v. drugs (22.6%) than U.S. women reported to have AIDS (26.5% were white; 51.0% had ever used i.v. drugs, p < 0.0001). In a multiple logistic regression model, specific attributes of individual trials did not influence enrollment of women with the exception that trials that targeted asymptomatic persons had greater enrollment of women. There was wide variation among research units in the percentage of women enrolled (1.0-37.5%), and evidence of significant regional variation in the ability of units to recruit available women. Units with female principal or coprincipal investigators had more than twice the percentage of female enrollment as units headed by men (10.8 vs. 5.3%, p < 0.001). Enrollment of women in a large HIV clinical trials program was low and appeared to be influenced more by demographic and geographic factors that attributes of specific trials. An apparent positive influence of female leadership on the enrollment of women warrants further study.


Effects of the mycotoxin nivalenol on bovine articular chondrocyte metabolism in vitro.
Kashin-Beck Disease (KBD) is an endemic, age-related degenerative osteoarthropathy and its cause is hypothesised to involve Fusarium mycotoxins. This study investigated the Fusarium mycotoxin Nivalenol (NIV) on the metabolism of bovine articular chondrocytes in vitro. The effect 0.0-0.5 µg/ml NIV on transcript levels of types I and II collagen, aggrecan, matrix metalloproteinases (MMPs), a disintegrin and metalloproteinase with thrombospondin motif (ADAMTS) and the tissue inhibitors of MMPs (TIMPs) was investigated using quantitative PCR. Amounts of sulphated glycosaminoglycans, MMPs and TIMPs were assessed using the Dimethylmethylene Blue assay, gelatin zymography and reverse gelatin zymography respectively. Cytoskeletal organisation was analysed using confocal microscopy and cytoskeletal gene and protein levels were measured by quantitative PCR and Western blot analysis, respectively. NIV caused a dose-dependent increase in aggrecan transcription with a concomitant retention of sGAG in the cell lysate. Furthermore, NIV significantly increased MMPs-2, -3 & -9, ADAMTS-4 and -5, and TIMP-2 and -3 transcript levels but inhibited type I collagen, MMP 1 and TIMP 1 mRNA levels. NIV promoted extensive cytoskeletal network remodelling, particularly with vimentin where a dose-dependent peri-nuclear aggregation occurred. NIV exposure to chondrocytes decreased matrix deposition, whilst enhancing selective catabolic enzyme production, suggesting its potential for induction of cellular catabolism. This NIV-induced extracellular matrix remodelling may be due to extensive remodelling/disassembly of the cytoskeletal elements. Collectively, these findings support the hypothesis that trichothecene mycotoxins, and in particular NIV, have the potential to induce matrix catabolism and propagate the pathogenesis of KBD.


Induction of allergic contact dermatitis by astigmatid mite-derived monoterpene, alpha-acaridial.
alpha-Acaridial [2(E)-(4-methyl-3-pentenyl)butenedial] is a novel monoterpene secreted from the house dust mites. Because of its molecular nature of a highly reactive, small lipidic compound, we addressed whether alpha-acaridial might function as a haptenic allergen that induced allergic contact dermatitis. Mice sensitized with alpha-acaridial were challenged by the same antigen on the ear skin. After 2 days, significant ear swelling with a prominent infiltration of CD4(+) T lymphocytes was observed. In vitro, alpha-acaridial exhibited an outstanding ability to quickly interact with and chemically modify a reference protein. Virtually all cysteine residues and a sizable fraction of lysine residues were found to be selectively modified, suggesting that alpha-acaridial could potentially interact with any proteins. Previously, numerous mite-derived proteinaceous allergens have been associated with contact dermatitis. Our study now emphasizes that small lipidic compounds released from mites comprise a new class of mite allergens, and therefore, is of significant medical implications.


Fission and fusion in island taxa--serendipity, or something to be expected?
A well-used metaphor for oceanic islands is that they act as 'natural laboratories' for the study of evolution. But how can islands or archipelagos be considered analogues of laboratories for understanding the evolutionary process itself? It is not necessarily the case that just because two or more related species occur on an island or archipelago, somehow, this can help us understand more about their evolutionary history. But in some cases, it can. In this issue of Molecular Ecology, Garrick et al. () use population-level sampling within closely related taxa of Galapagos giant tortoises to reveal a complex demographic history of the species Chelonoidis becki - a species endemic to Isabela Island, and geographically restricted to Wolf Volcano. Using microsatellite genotyping and mitochondrial DNA sequencing, they provide a strong case for C. becki being derived from C. darwini from the neighbouring island of Santiago. But the interest here is that colonization did not happen only once. Garrick et al. () reveal C. becki to be the product of a double colonization event, and their data reveal these two founding lineages to be now fusing back into one. Their results are compelling and add to a limited literature describing the evolutionary consequences of double colonization events. Here, we look at the broader implications of the findings of Garrick et al. () and suggest genomic admixture among multiple founding populations may be a characteristic feature within insular taxa.


[Isolation and identification of Bacillus cereus strain Jp-A and its capability in phenol degradation].
In this study, a bacterial strain named as Jp-A was isolated from the activated sludge of a steel factory. Through morphological observation,physiological and biochemical test, and 16srRNA sequence analysis, the strain was identified as Bacillus cereus. Under laboratory condition, the phenol at its initial concentration of 5,10 and 15 mmol x L(-1) could be completely degraded by the strain within 16,24 and 32 h, respectively, but the growth of the strain was inhibited when the phenol concentration was 30 mmol x L(-1). The strain could also utilize and degrade other aromatic hydrocarbons, e. g. , benzene, toluene, chlorophenol and nitrophenol, as its sole source of carbon and energy. Dioxygenase test indicated that the strain degraded phenol via meta-pathways. The key enzyme catechol 2,3-dioxygenase was an induced enzyme, which was mainly located on the cell membrane, and adding glucose could inhibit its generation.


Inhibitory effects of oxatomide on several activities of SRS-A and synthetic leukotrienes in guinea-pigs and rats.
Effects of oxatomide, an orally active anti-allergic drug, on several activities of slow reacting substance of anaphylaxis (SRS-A) and synthetic leukotrienes (LT) C4, D4 and E4 were investigated. In addition, such activities of oxatomide were compared with those of FPL-55712. Oxatomide, at a concentration of 3 X 10(-8) M or higher, inhibited the phasic contractions of isolated guinea-pig ileum induced by partially purified SRS-Agp and SRS-Arat which were anaphylactically generated from guinea-pig lung fragments and rat peritoneal cavities, respectively. The 50% inhibitory concentrations (IC 50) of oxatomide to the contractions by SRS-Agp and SRS-Arat are 2.7 +/- 0.9 X 10(-7) M and 1.6 +/- 0.3 X 10(-7) M, respectively. Oxatomide also inhibited the LTC4, LTD4, histamine or serotonin-induced contractions of ileum. FPL-55712, a specific SRS-A antagonist, inhibited SRS-Agp, SRS-Arat, LTC4 or LTD4-induced contractions at concentrations ranging from 10(-9) M to 10(-6) M without affecting histamine and serotonin responses. Oxatomide produced dose-dependent relaxations of isolated guinea-pig tracheal and lung parenchymal strips precontracted with LTD4 and histamine. Oxatomide, at doses 10 and 30 mg/kg (p.o.), inhibited significantly the increase in vascular permeability produced by LTC4, LTE4, histamine and serotonin in rats. These results suggest that, although less effective and less selective as compared with FPL-55712, oxatomide exerts inhibitory effects on SRS-A activities, and that such effects could partly explain the anti-allergic effects of the compound.


Significant differences in parameters of glucose metabolism in children of hypertensive and normotensive parents.
In the recent years, alterations in the carbohydrate metabolism, including insulin resistance, are considered as risk factors in the development of hypertension and its complications in young age. Hypertension is associated with significant cardiovascular morbidity and mortality. The onset of pathology responsible for the development of hypertension, as well as levels of biomarkers specific for early stages of atherosclerosis are poorly understood. To compare a group of children whose parents have a history of hypertension (study group) with a group of children with normotensive parents (reference group), with consideration of typical risk factors for atherosclerosis, parameters of lipid and carbohydrate metabolism, anthropometric data and new biomarkers of early cardiovascular disease (hsCRP, adiponectin, sICAM-1). The study population consists of 84 children. Of these, 40 children (mean age 13.6±2.7 years) had a parental history of hypertension, and 44 aged 13.1±3.7 yrs were children of normotensive parents. Anthropometric measurements were taken, and measurements of blood pressure, lipid profile, glucose and insulin levels were carried out. The insulin resistance index (HOMA IR) was calculated. Levels of hsCRP, soluble cell adhesion molecules (sICAM) and adiponectin were measured. There were no statistically significant differences in anthropometric parameters (body mass, SDS BMI, skin folds) between groups. Values of systolic blood pressure were statistically significantly higher in the study group (Me 108 vs. 100 mmHg, p= 0.031), as were glycaemia (Me 80 vs. 67 mg/dl p<0.001) and insulinaemia levels (Me 8.89 vs. 5.34 µIU/ml, p=0.024). Higher, statistically significant values of HOMA IR were found in the study group (children of hypertensive parents) (Me 1.68 vs. 0.80 mmol/l × mU/l, p=0.007). Lower adiponectin levels (Me 13959.45 vs. 16822 ng/ml, p=0.020) were found in children with a family history of hypertension. No significant differences were found in the levels of sICAM, hsCRP, and parameters of lipid metabolism. Family history of hypertension is correlated with higher values of systolic blood pressure and higher values of parameters for carbohydrate metabolism in children. Hypertension in parents is a risk factor for cardiovascular disease in their children.


Dexamethasone suppression test in the management of hyperandrogenized patients.
The authors evaluated 86 hyperandrogenized women with measurements of serum cortisol, dehydroepiandrosterone sulfate, testosterone, and dihydrotestosterone in pooled sera before and after a dexamethasone suppression test. According to strict criteria, 70 (81%) of 86 women demonstrated a major glucocorticoid-suppressible component to their hyperandrogenism. Endocrine therapy was dictated by the results of the dexamethasone suppression test. To assess the predictive value of this test, we evaluated the clinical responses of the subgroup of 55 women who received appropriate endocrine suppression therapy for 6 to 15 months. Of this subgroup, 38 were identified as having adrenal hyperandrogenism; 3 had ovarian hyperandrogenism; and 14 had mixed hyperandrogenism. Of the 55 patients, 49 received dexamethasone alone; 3 received dexamethasone plus Ovral (an oral contraceptive containing the synthetic progestogen norgestrel 0.5 mg and ethinyl estradiol 0.05 mg); and 3, all with ovarian hyperandrogenism, received depomedroxyprogesterone acetate (Depo-Provera). Clinical response was assessed in terms of improvement or no improvement in menstrual status, acne, and hirsutism. Of 29 patients with adrenal or mixed hyperandrogenism associated with abnormal menses, the menstrual status of 17 (59%) improved after dexamethasone therapy. Acne improved in 39 (100%) of 39 subjects. Hirsutism showed moderate to marked improvement in 40 (73%) of 55 women after 6 to 15 months of endocrine suppression therapy. These results indicate the endocrine suppression therapy, particularly with repeated low-dose dexamethasone, prescribed on the basis of a dexamethasone suppression test, is an effective means of managing hyperandrogenism.


Dual-phase helical CT of pancreatic adenocarcinoma: assessment of resectability before surgery.
The aim of our study was to prospectively evaluate the accuracy of dual-phase helical CT in the preoperative assessment of resectability in patients with suspected pancreatic cancer using surgical and histopathologic correlation. Between January 1999 and December 2000, 76 patients with suspected pancreatic cancer underwent preoperative evaluation and staging with dual-phase helical CT (3-mm collimation for pancreatic phase, 5-mm collimation for portal phase). Iodinated contrast material was injected IV (170 mL at a rate of 4 mL/sec); acquisition began at 40 sec during the pancreatic phase and at 70 sec during the portal phase. Three radiologists prospectively evaluated the imaging findings to determine the presence of pancreatic tumor and signs of unresectability (liver metastasis, vascular encasement, or regional lymph nodes metastasis). The degree of tumor-vessel contiguity was recorded for each patient (no contiguity with tumor, contiguity of < 50%, or contiguity of > or =50%). Thirty-nine patients with pancreatic adenocarcinoma were surgically explored. Curative resections were attempted in 34 patients and were successful in 25. The positive predictive value for resectability was 73.5%. Nine patients considered resectable on the basis of CT findings were found to be unresectable at surgery because of liver metastasis (n = 5), vascular encasement (n = 2), or lymph node metastasis (n = 2). We found that the overall accuracy of helical CT as a tool for determining whether a pancreatic adenocarcinoma was resectable was 77% (30/39 patients). Dual-phase helical CT is a useful technique for preoperative staging of pancreatic cancer. The main limitation of CT is that it may not reveal small hepatic metastases.


The efficacy and selectivity of tumor cell killing by Akt inhibitors are substantially increased by chloroquine.
This study was to evaluate the enhancement value of chloroquine (CQ) in cancer cell killing when used in combination with Akt inhibitors. The results showed that the combination of CQ and Akt inhibitors is much more effective than either one alone. Importantly, the CQ-mediated chemosensitization of cell killing effects by Akt inhibitors is cancer specific. In particular, when combined with 10 microM CQ, 1,3-dihydro-1-(1-((4-(6-phenyl-1H-imidazo[4,5-g]quinoxalin-7-yl)phenyl)methyl)-4-piperidinyl)-2H-benzimidazol-2-one (an Akt1 and 2 inhibitor; compound 8) killed cancer cells 10-120 times more effectively than normal cells. Thus, CQ is a very effective and cancer-specific chemosensitizer when used in combination with Akt inhibitors.


Transmitted drug resistance mutations and trends of HIV-1 subtypes in treatment-naïve patients: A single-centre experience.
Transmitted drug resistance (TDR) and HIV-1 genetic diversity may affect treatment efficacy and clinical outcomes. Here we describe the circulating viral subtypes and estimate the prevalence of drug resistance among antiretroviral therapy (ART)-naïve patients attending Sapienza University Hospital (Rome, Italy) from 2006-2017. Genotypic resistance testing (GRT) was performed on 668 ART-naïve patients for integrase (n = 52), protease and reverse transcriptase (n = 668) sequences. Twenty-one different HIV-1 subtypes and circulating recombinant forms (CRFs) were identified. Subtype B was the most common (67.1%), followed by CRF02_AG (8.4%), and subtypes C and F (both 6.0%). A significantly increase in the proportion of non-B strains (P < 0.001) and the rate of non-Italian patients was observed over time. The overall prevalence of TDR was 9.4% (NRTI, 4.2%; NNRTI, 5.8%; and PI, 1.0%) and was higher in subtype B strains. Transmitted INSTI mutations (Q148H and G140S) responsible for high-level resistance to raltegravir and elvitegravir and intermediate resistance to dolutegravir and bictegravir were found, for the first time, in two individuals. Minor or accessory INSTI mutations were detected in 17.3% of patients. No significant decrease in the prevalence of TDR was documented over time. The significant increase in non-B subtypes suggests that the molecular epidemiology of HIV-1 is changing. Detection of a major INSTI mutation in two ART-naïve patients highlights the importance of performing GRT before commencing treatment. This finding and the lack of a significant reduction in TDRs underline the importance of continuous surveillance of resistance mutations.


Improved Quantification of Cell Density in the Arterial Wall-A Novel Nucleus Splitting Approach Applied to 3D Two-Photon Laser-Scanning Microscopy.
Accurate information on vascular smooth muscle cell (VSMC) content, orientation, and distribution in blood vessels is indispensable to increase understanding of arterial remodeling and to improve modeling of vascular biomechanics. We have previously proposed an analysis method to automatically characterize VSMC orientation and transmural distribution in murine carotid arteries under well-controlled biomechanical conditions. However, coincident nuclei, erroneously detected as one large nucleus, were excluded from the analysis, hampering accurate VSMC content characterization and distorting transmural distributions. In the present study, therefore, we aim to (1) improve the previous method by adding a "nucleus splitting" procedure to split coinciding nuclei, (2) evaluate the accuracy of this novel method, and (3) test this method in a mouse model of VSMC apoptosis. After euthanasia, carotid arteries from SM22α-hDTR Apoe -/- and control Apoe -/- mice were bluntly dissected, excised, mounted in a biaxial biomechanical tester and brought to in vivo axial stretch and a pressure of 100 mmHg. Nuclei and elastin fibers were then stained using Syto-41 and Eosin-Y, respectively, and imaged using 3D two-photon laser scanning microscopy. Nuclei were segmented from images and coincident nuclei were split. The nucleus splitting procedure determines the likelihood that voxel pairs within coincident nuclei belong to the same nucleus and utilizes these likelihoods to identify individual nuclei using spectral clustering. Manual nucleus counts were used as a reference to assess the performance of our splitting procedure. Before and after splitting, automatic nucleus counts differed -26.6 ± 9.90% (p < 0.001) and -1.44 ± 7.05% (p = 0.467) from the manual reference, respectively. Whereas the slope of the relative difference between the manual and automated counts as a function of the manual count was significantly negative before splitting (p = 0.008), this slope became insignificant after splitting (p = 0.653). Smooth muscle apoptosis led to a 33.7% decrease in VSMC density (p = 0.008). Nucleus splitting improves the accuracy of automated cell content quantification in murine carotid arteries and overcomes the progressively worsening problem of coincident nuclei with increasing cell content in vessels. The presented image analysis framework provides a robust tool to quantify cell content, orientation, shape, and distribution in vessels to inform experimental and advanced computational studies on vascular structure and function.


Quantification of alphafetoprotein (AFP) endocytosis by PHA-activated peripheral blood mononuclear cells (PBMC) from HIV-infected individuals. A useful test of predictive value for the progression of AIDS.
Serum alphafetoprotein (AFP) is actively taken up, through receptor-mediated endocytosis, by many embryo-fetal cells during ontogenic development but also by neoplastic cells, as well as by normal peripheral T lymphocytes after mitogenic activation. We have previously shown that the ability to internalize AFP is impaired in mitogen-activated T cells from several groups of (HIV+)-seropositive individuals and that this expression roughly correlates with the progression of the disease. It is not clear whether this impaired AFP-endocytosis results from an HIV-mediated inhibition of AFP-receptor expression or if it is the consequence of a target signal transduction impairment due to HIV-infection. In the present work we have explored both possibilities by studying AFP-endocytosis in peripheral blood mononuclear cells (PBMC) from seropositive (HIV+)-asymptomatic heterosexual individuals and in in vitro HIV-infected PBMC from healthy donors, either quiescent or stimulated with phytohemagglutin (PHA). Our results suggest that this novel abnormality of T-cells associated with HIV-infection reflects an unusual proliferative response of PBMC to mitogenic stimuli.


Efficacy of a Mandibular Advancement Appliance on Sleep Disordered Breathing in Children: A Study Protocol of a Crossover Randomized Controlled Trial.
Sleep-Disordered Breathing (SDB) varies from habitual snoring to partial or complete obstruction of the upper airway and can be found in up to 10% of children. SDB can significantly affect children's wellbeing, as it can cause growth disorders, educational and behavioral problems, and even life-threatening conditions, such as cardiorespiratory failure. Adenotonsillectomy represents the primary treatment for pediatric SDB where adeno-tonsillar hypertrophy is indicated. For those with craniofacial anomalies, or for whom adenotonsillectomy or other treatment modalities have failed, or surgery is contra-indicated, mandibular advancement splints (MAS) may represent a viable treatment option. Whilst the efficacy of these appliances has been consistently demonstrated in adults, there is little information about their effectiveness in children. To determine the efficacy of mandibular advancement appliances for the management of SDB and related health problems in children. The study will be designed as a single-blind crossover randomized controlled trial with administration of both an "Active MAS" (Twin-block) and a "Sham MAS." Eligible participants will be children aged 8-12 years whose parents report they snore ≥3 nights per week. Sixteen children will enter the full study after confirming other inclusion criteria, particularly Skeletal class I or class II confirmed by lateral cephalometric radiograph. Each child will be randomly assigned to either a treatment sequence starting with the Active or the Sham MAS. Participants will wear the appliances for 3 weeks separated by a 2-week washout period. For each participant, home-based polysomnographic data will be collected four times; once before and once after each treatment period. The Apnea Hypopnea Index (AHI) will represent the main outcome variable. Secondary outcomes will include, snoring frequency, masseter muscle activity, sleep symptoms, quality of life, daytime sleepiness, children behavior, and nocturnal enuresis. In addition, blood samples will be collected to assess growth hormone changes. This study was registered in the Australian New Zealand Clinical Trials Registry (ANZCTR): [ACTRN12614001013651].


A Measurement Setup and Automated Calculation Method to Determine the Charge Injection Capacity of Implantable Microelectrodes.
The design of safe stimulation protocols for functional electrostimulation requires knowledge of the "maximum reversible charge injection capacity" of the implantable microelectrodes. One of the main difficulties encountered in characterizing such microelectrodes is the calculation of the access voltage Va. This paper proposes a method to calculate Va that does not require prior knowledge of the overpotential terms and of the electrolyte (or excitable tissue) resistance, which is an advantage for in vivo electrochemical characterization of microelectrodes. To validate this method, we compare the calculated results with those obtained from conventional methods for characterizing three flexible platinum microelectrodes by cyclic voltammetry and voltage transient measurements. This paper presents the experimental setup, the required instrumentation, and the signal processing.


[Antibiotic-associated colitis in senile patients].
Antibiotic-associated colitis (AAC) is a relatively frequent disorder in the senile population. Because of the change of life style in the elderly, the clinical pattern of AAC may be varied. The causative antibiotics, duration of administration, duration from taking antibiotics to onset of symptoms, background disorders, symptoms, laboratory data, therapies and prognosis in patients with AAC were investigated retrospectively in 54 cases of averaging 80.5 year old in this hospital. The patients with pseudomembranous colitis (PMC) are older and with a greater preponderance of female gender than patients with acute hemorrhagic colitis. Antimicrobial agents that frequently induced AAC are cephalosporins and penicillins. Symptoms in patients with PMC are diarrhea, abdominal cramping pain and fever. The most common background diseases were neurological and psychiatric disorders. Furthermore, recent advances in understanding the mechanism of toxin A-mediated colinic inflammation, and the management of AAC are reported.


[De Novo renal mass on kidney grafts.]
Cancer is the 3rd cause of death in the Spanish kidney transplant population. The risk of developing a tumour is multifactorial. Improvements in follow-up and increased graft survival have led to an increase in the incidence of de novo tumours in these patients. We have conducted a systematic review of articles published in online medical databases related to de novo tumours in kidney transplant recipients. We have evaluated the incidence of de novo neoplasms in patients who under went a kidney transplant at the Hospital Universitario de Cruces from January 2011 to December 2018. RESULTS AND DISCUSSION: Different characteristics have been described within the transplanted population that could promote the development of tumours. The alteration of the antitumor response, the altered ability to respond to infections, drug´s carcinogenic effect, and agreater susceptibility ultraviolet rays damage are some of the most repeated. As a consequence, overall risk of cancer increases two to three times in the transplanted population. Overall, in our analysis, the neoplasms that showed the highest incidence were urological (21.98%), followed by haematological (16.63%) and digestive tract (14.58%). There is a higher incidence and risk of de novo tumour development in the kidney transplant population, which probably requires optimizing patient follow-up and developing more precise screening strategies that can be modified depending on geographic and individual variations, to reduce the impact on survival that it may have on our patients.


Use of Ambulatory Patch Monitoring Devices to Supplement Inpatient Telemetry-A Descriptive Study of a Single-center Experience During the Coronavirus Disease 2019 Pandemic.
To accommodate the surge in patients with coronavirus disease 2019 during the spring of 2020, outpatient areas in our health system were repurposed as inpatient units. These spaces often lacked the same resources as the standard inpatient unit, including telemetry equipment. We utilized mobile cardiac outpatient telemetry (MCOT) in place of traditional telemetry and suggest that MCOT is an appropriate substitution only for patients at low risk of developing arrhythmia given the prolonged time to notification of the care team regarding events and imprecise measurements of the corrected QT interval when compared to 12-lead electrocardiography.


[Dual diagnosis in psychoactive substance abusing or dependent persons].
There has been noticed a systematic growth of using psychoactive substance (SP) in last years. The co-occurrence of mental and physical disorders related to substance abuse of treated patients is more often a serious problem to medical services. Dual diagnosis (DD) is a clinical term referring to co-morbidity or the co-occurrence in the same individual of a psychoactive substance use disorder and another psychiatric disorder. The aim of the study is to investigate the prevalence of dual diagnosis in patients with diagnosis of substance use disorder hospitalized in years 1994-2005, to assess the kind of co-morbid mental disorders and the course of treatment in three groups: patients with DD, with diagnosis of mental disorder without substance use and with diagnosis related to substance use. The retrospective study of 4 349 case records of patients hospitalized in the department of psychiatry in years 1994-2005. Out of this number two groups of patients were separated: persons abusing or dependent on SP (n = 825) and patients with dual diagnosis (n = 362). The control group (n = 200) was created among patients with mental disorders and without SP abuse. Socio-demographic factors, number and the length of hospitalizations, aggressive behaviours, suicide attempts, discharges from hospital on demand were analyzed. In the DD group there was an attempt to evaluate the relation between substance use disorders and co-occuring mental disorders performed. The frequency of DD among all patients hospitalized in the studied period of time was 8.3%, whereas among patients abusing SP was 30.5%. This study demonstrates that patients with the DD are statistically longer hospitalized, discharged from hospitals at their own request and more often need treatment in hospitals, statistically more often try to commit suicide and perform aggressive behavior. Mental disorders were substantially often secondary to substance related disorders in the DD group. There was proved that patients mainly abused alcohol and the most frequent mental disorder were mood (affective) disorders.


[Differentiation of an outcome sample in elective labor induction with PGE2 by the oxytocin sensitivity test].
The goal of the present study was to evaluate whether the implementation of an oxytocin sensitivity test in addition to pelvic scoring would improve prediction of successful induction and could lead to a further reduction in the already low rate of protracted labour and operative deliveries in cases of elective induction by means of prostaglandin (PG) E2 tablets. In order to establish the optimal dosage we compared the endocervical application of 1.5 mg PG E2 with 3 mg intravaginally. Out of 158 women without risk factors examined at term 73.5% decided to have labour induced. In the induction groups given endocervical or intravaginal PG E2 the delivery intervals were significantly shorter and the rate of operative deliveries was reduced. In comparison with those women who decided to await spontaneous onset of labour, the fetal outcome was, however, the same. The endocervical application of 1.5 mg PG E2 did not prove any better than 3 mg given intravaginally. The performance of a pretherapeutic oxytocin sensitivity test yielded additional information about the chances of inducing labour successfully. The results confirmed the efficacy and acceptance of this method of inducing labour.


Natural killer cells prevent direct anterior-to-posterior spread of herpes simplex virus type 1 in the eye.
Anterior chamber (AC) inoculation of the KOS strain of herpes simplex virus type 1 (HSV-1) results in morphologic sparing of the ipsilateral retina, whereas the retina of the uninoculated contralateral eye becomes infected and undergoes acute retinal necrosis. Natural killer (NK) cells are an important component of the primary immune response to most virus infections. The purpose of this study was to determine whether NK cells are involved in preventing early direct anterior-to-posterior spread of HSV-1 after AC inoculation. Normal BALB/c mice were inoculated with 4 X 10(4) plaque-forming units (PFU) of the KOS strain of HSV-1 using the AC route. NK activity was measured in the spleen, the superficial cervical and submandibular lymph nodes, and the inoculated eye by lysis of chromium-labeled, NK-sensitive YAC-1 target cells. Histopathologic scoring and immunohistochemical staining for HSV-1 were performed in NK-depleted (injected intravenously with anti-asialo GM1) or mock-depleted (injected intravenously with normal rabbit serum) mice. In mock-depleted mice, NK activity in the spleens, superficial cervical and submandibular lymph nodes, and inoculated eyes peaked at postinoculation (pi) day 5 and declined by pi day 7. Treatment with anti-asialo GM1 eliminated NK activity in the eye and at nonocular sites. The histopathologic scores at pi day 5 indicated more damage to the retinas of NK-depleted mice than to those of mock-depleted mice, and immunohistochemical staining for HSV-1 showed spread of the virus to the sensory retina only in NK-depleted mice. NK cells were activated within 5 days after AC inoculation of the KOS strain of HSV-1. Activation of NK cells appears to play a role in preventing direct anterior-to-posterior spread of the virus in the inoculated eye which, in turn, protects the retina of this eye and helps to explain why the architecture of the retina of this eye is spared.


Crystal structure of the C-terminal tetrad repeat from synexin (annexin VII) of Dictyostelium discoideum.
Synexin (annexin VII) is a cytosolic Ca(2+)-binding protein that promotes membrane fusion and forms voltage-regulated ion channels in artificial and natural membranes. The crystal structure of the C-terminal tetrad repeat from recombinant synexin (annexin VII) of Dictyostelium discoideum was solved to 2.45 A resolution. The protein crystallized in a dimeric form with two molecules joined face-to-face by their convex sides. Mainly hydrogen bonds and van der Waals contacts are involved in dimer formation, while not Ca2+ is bound to the conserved Ca(2+)-binding sites. The truncated N terminus is folded into a short antiparallel beta-sheet, from which the side-chain of Tyr111 penetrates sideways into the central, hydrophilic pore and may directly affect the ion channel activity. In order to investigate the structure of the missing N-terminal domain, we synthesized a 37-membered peptide of the N-terminal tail, (GYPPQQ)6G. CD and NMR studies showed a random coil conformation of the peptide in solution, suggesting for the synexin N terminus the lack of a well-ordered, three-dimensional fold.


Aldosterone up-regulates mRNA for the alpha3 and beta1 isoforms of (Na,K)-ATPase in several brain regions from adrenalectomized rats.
In physiological doses, mineralocorticoids (MC) normalize the high salt intake developed after adrenalectomy. We have studied whether this effect of MC is accompanied by changes in the mRNA of neuronal alpha3 and beta1 subunits of the (Na,K)-ATPase because this enzyme could by a mediator of MC action in target cells. We employed [35S]oligonucleotide probes for the mentioned subunits hybridized to brain sections from adrenalectomized rats and adrenalectomized rats receiving aldosterone (ALDO) during 4 days. Using t-test statistics to measure differences in mean levels of grain density, and the Kolmogorov-Smirnov non-parametric test applied to frequency histograms, we showed that ALDO increased the alpha3 subunit mRNA in the septum medialis, preoptic area medialis, caudate-putamen, periventricular gray substance, amygdala lateralis, hippocampal subfields CA1 to CA4 and the gyrus dentatus. Significant increases for the beta1 subunit mRNA were found in periventricular gray substance, the CA1-CA4 hippocampal subfields and gyrus dentatus. Therefore, the salt-suppression effect of MC was accompanied by coordinate increases in (Na,K)-ATPase alpha3 and beta1 subunit mRNA in the hippocampus, gyrus dentatus and periventricular gray substance, whereas in other regions the stimulatory effect was exclusive of the alpha3 subunit mRNA only. The results suggest that the enzyme could be a target of ALDO action not only in areas related to salt appetite control (amygdala, preoptic area) but also in brain regions subserving other functions of the MC.


Genetic adaptation by Pseudomonas aeruginosa to the airways of cystic fibrosis patients.
In many human infections, hosts and pathogens coexist for years or decades. Important examples include HIV, herpes viruses, tuberculosis, leprosy, and malaria. With the exception of intensively studied viral infections such as HIV/AIDs, little is known about the extent to which the clonal expansion that occurs during long-term infection by pathogens involves important genetic adaptations. We report here a detailed, whole-genome analysis of one such infection, that of a cystic fibrosis (CF) patient by the opportunistic bacterial pathogen Pseudomonas aeruginosa. The bacteria underwent numerous genetic adaptations during 8 years of infection, as evidenced by a positive-selection signal across the genome and an overwhelming signal in specific genes, several of which are mutated during the course of most CF infections. Of particular interest is our finding that virulence factors that are required for the initiation of acute infections are often selected against during chronic infections. It is apparent that the genotypes of the P. aeruginosa strains present in advanced CF infections differ systematically from those of "wild-type" P. aeruginosa and that these differences may offer new opportunities for treatment of this chronic disease.


Update on selected renal cell tumors with clear cell features. With emphasis on multilocular cystic clear cell renal cell carcinoma.
Clear cell renal cell carcinoma (CCRCC) is the most common malignant tumor of renal epithelial origin and, with the exception of some rare tumors, the most deadly. The exception is represented by the multilocular cystic CCRCC, whose prognosis is excellent with survival rates of 100% when diagnosis is made according to the WHO definition. For this reason a proposal has been made to rename this tumor as multilocular cystic renal cell neoplasms of low malignant potential. Another exemption could be the clear cell (tubulo) papillary renal cell carcinoma/clear cell papillary renal cell carcinoma (CCPRCC), a tumor with tubulopapillary architecture and clear cytoplasm. Published data indicates that these are neoplasms with indolent clinical behavior. No cases with metastasis have been reported. Neoplasms meeting criteria for CCPRCC will subsequently be reclassified as of "low malignant potential" rather than carcinoma. The stroma of CCPRCC not infrequently demonstrates smooth muscle metaplasia. It should be remembered, however, that smooth muscle stromal metaplasia and proliferation are not entirely specific to this entity. Hence, it is suggested that smooth muscle metaplasia in the kidney may be a nonspecific common reaction to a variety of stimuli. Xp11 translocation renal cell carcinomas are a group of neoplasms distinguished by chromosomal translocations with breakpoints involving the TFE3 transcription factor gene, which maps to the Xp11.2 locus. The most distinctive histologic pattern of the Xp11 translocation renal cell carcinoma is that of a neoplasm with both clear cells and papillary architecture, and abundant psammoma bodies. TFE3 immunohistochemical staining is reported to be sensitive and specific for a diagnosis of translocation-associated carcinoma as long as the labeling is strong, diffuse, and nuclear. This immunostaining is particularly useful if the differential diagnosis includes CCRCC and CCPRCC. In conclusion, recognition of CCRCC and differentiation from other renal cell neoplasms with clear cytoplasm is important not only for prognostication but also for treatment-related reasons.


Attitudes toward the level of men's involvement in abortion decisions.
College students completed a questionnaire that assessed their attitudes toward the level of male responsibility in abortion decisions. Overall, both men and women thought that men should have some degree of involvement in the abortion decision. However, as expected by the first hypothesis, men indicated a desire for more responsibility in the abortion decision than women thought the men should have. A second hypothesis predicted women would feel more strongly than men that abortion was strictly a woman's issue. Contrary to the hypothesis, women tended to disagree that abortion was strictly a women's issue. Implications of the findings are discussed.


Total GABA level in human auditory cortex is associated with speech-in-noise understanding in older age.
Speech-in-noise (SIN) understanding often becomes difficult for older adults because of impaired hearing and aging-related changes in central auditory processing. Central auditory processing depends on a fine balance between excitatory and inhibitory neural mechanisms, which may be upset in older age by a change in the level of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). In this study, we used MEGA-PRESS magnetic resonance spectroscopy (MRS) to estimate GABA levels in both the left and right auditory cortices of young and older adults. We found that total auditory GABA levels were lower in older compared to young adults. To understand the relationship between GABA and hearing function, we correlated GABA levels with hearing loss and SIN performance. In older adults, the GABA level in the right auditory cortex was correlated with age and SIN performance. The relationship between chronological age and SIN loss was partially mediated by the GABA level in the right auditory cortex. These findings support the hypothesis that inhibitory mechanisms in the auditory system are reduced in aging, and this reduction relates to functional impairments.


Pre-eclampsia: aspirin beneficial.
Two meta-analyses suggest that low-dose aspirin taken daily during pregnancy reduces the incidence of pre-eclampsia in women at risk and reduces mortality among the infants born to mothers at high risk of pre-eclampsia.


Ethical issues in forensic psychiatric research on mentally disordered offenders.
This paper analyses ethical issues in forensic psychiatric research on mentally disordered offenders, especially those detained in the psychiatric treatment system. The idea of a 'dual role' dilemma afflicting forensic psychiatry is more complicated than acknowledged. Our suggestion acknowledges the good of criminal law and crime prevention as a part that should be balanced against familiar research ethical considerations. Research aiming at improvements of criminal justice and treatment is a societal priority, and the total benefit of studies has to be balanced against the risks for research subjects inferred by almost all systematic studies. Direct substantial risks must be balanced by health benefits, and normal informed consent requirements apply. When direct risks are slight, as in register-based epidemiology, lack of consent may be counter-balanced by special measures to protect integrity and the general benefit of better understanding of susceptibility, treatment and prevention. Special requirements on consent procedures in the forensic psychiatric context are suggested, and the issue of the relation between decision competence and legal accountability is found to be in need of further study. The major ethical hazard in forensic psychiatric research connects to the role of researchers as assessors and consultants in a society entertaining strong prejudices against mentally disordered offenders.


Instrumentation in Maxillofacial Surgery: Few Practical Tips.
When a newly inducted plastic surgery resident embarks on maxillofacial surgery, with drills, screws, plates and burrs, it seems like a new domain altogether. As a new resident, it is truly fascinating as to how such wide variety of bony work is done without scarring over the face. Here we discuss a few practical tips which the author has learned during his surgical sojourn in residency. It is hoped that the readers who are new to maxillofacial surgery, shall find these useful.


A Biochemical Analysis of the Stapes.
BACKGROUND Otosclerosis is a primary disease of the bony labyrinth. In the course of otosclerosis, abnormal resorption and recalcification of the endochondral layer of the temporal bone is observed. The otosclerotic process most commonly develops in the anterior part of the oval window. MATERIAL AND METHODS We analyzed stapes superstructures from 4 patients undergoing surgery for otosclerosis. The first step involved tissue assessment under a scanning electron microscope. The resulting images were analyzed in terms of morphological changes. The stapes superstructure was then divided into small "ossicles", including fragments from the closest vicinity of the stapes footplate and a fragment of the head of the stapes. This material was examined using a scanning electron microscope with a unit for chemical analysis in microareas. RESULTS Chemical analysis confirms the appearance of considerable quantities of the following elements: carbon, oxygen, potassium, and calcium, and the appearance of small quantities of sodium and magnesium. Based on a detailed analysis of the chemical composition, these fragments could represent a calcium phosphate compound from the following system: CaO-P₂O₅-H₂O. Fragments of the superstructure from the region closest to the base of the stapes demonstrated a considerably larger presence of carbon, oxygen, and nitrogen, which most likely suggests an increased metabolic process in this region. CONCLUSIONS Our analysis revealed an increased metabolic activity in the closest vicinity of the otosclerotic focus, the fissula ante fenestram. The increased metabolism correlated with the bone tissue changes seen on scanning electron microscopy.


Electroretinographic profile in emmetropic Singaporean eyes.
To characterise the electroretinographic (ERG) profile in 70 Singaporean emmetropic eyes. Seventy eyes of thirty-five patients with refractive error of -1.00D or less and with a normal ophthalmic examination were chosen. They were subjected to three flash patterns generated with a Nihon-Kohden Flash Stimulator. The results were captured on a Nihon-Kohden Neuropack 8. The mean age of the patients was 25 years (range 20 to 30). The mean spherical refractive error was -0.3D (range 0D to -1.00D). For the scotopic dim flash, the mean amplitude for the 'b' wave was 304.6 +/- 69.2 mu v (range 175 mu v to 469 mu v) and the mean latency was 47.56 +/- 4.87 ms (range 41.2 ms to 62.0 ms). For the scotopic bright flash, the mean amplitude for the 'b' wave was 469.54 +/- 127.15 mu v (range 257 mu v to 750 mu v) and the mean latency was 40.54 +/- 3.91 ms (range 32.0 ms to 48.9 ms). In the flicker response, the mean amplitude for the 'b' wave was 34.19 +/- 12.97 mu v (range 14 mu v to 64 mu v) with mean latency at 34.46 +/- 0.58 ms (range 33.1 ms to 35.9 ms). With ERG normal values so generated, comparisons with these can then be made for abnormal cases.


Relation between the wave front and the tip movement of spirals.
The relation between the movement of spiral waves and their tip for a simple spiral is experimentally investigated in a spatial open reactor using the Belousov-Zhabotinsky reaction. In the quasi-two dimensional regime, our results agree with the combustion model proposed by Lázár et al. [Chaos 5, 443 (1995)] which states that the speed of spiral tip movement is proportional to the speed of spiral waves, c(tip) infinity c(front), when expressed in the radius of the spiral tip trajectory R and the spiral wavelength lambda, R infinity lambda. The measurement shows that the slope of the linear R-lambda curve is about 0.13, independent of the control parameter. This observation is also consistent with the combustion model.


TIGIT, A Novel Therapeutic Target for Tumor Immunotherapy.
Co-inhibitory and co-stimulatory receptors act in concert to regulate adaptive immune cell function, and the balance of these receptors is essential for the maintenance of immune homeostasis. Tumors constitute highly suppressive microenvironments in which elevated expression of co-inhibitory receptors on tumor-infiltrating lymphocytes (TILs) is often found. Functional blockade of the co-inhibitory receptors such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death 1 (PD-1) have yielded encouraging outcomes in tumors, generating substantial interest in seeking for additional co-inhibitory molecules that may act as potential interfering targets. T-cell Ig and ITIM domain (TIGIT) is a newly identified co-inhibitory receptor expressed by regulatory T cells (Tregs), activated T cells, and natural killer (NK) cells. Several groups reported consistently that TIGIT expression was elevated on CD8+ TILs and Tregs in a variety of tumors. Moreover, TIGIT blockade has exhibited therapeutic benefits in animal models of different tumors. Therefore, TIGIT upregulation plays an important role in tumor immunity and may serve as a promising therapeutic target for tumor management.


Sudden cardiac death and coronary disease in the young: A nationwide cohort study in Denmark.
Sudden cardiac death caused by coronary artery disease (CAD-SCD) is the most frequent cause of SCD in persons <50years. The aim of this study was to examine differences in clinical characteristics and autopsy findings of the heart among 18-35 and 36-49year old CAD-SCD cases. We have previously identified all sudden cardiac deaths in Denmark through review of death certificates and autopsy reports including all deaths between 2000 and 2006 in individuals aged 18-35years and all deaths between 2007 and 2009 in individuals aged 18-49years. In this study we included the 197 autopsied CAD-SCD cases. Full autopsy report and medical records from general practitioners and hospitals were obtained. There was a male predominance (n=151, 76%) and the median age was 42years. In witnessed cases, 51% had a shockable rhythm and 9 cases returned to spontaneous circulation briefly, CAD-SCD victims aged 36-49years had more severe atherosclerosis in all coronary arteries, more multi-vessel disease (29% vs. 15%, p=0.049) and less commonly (38% vs. 54%, p=0.039) acute coronary occlusion than victims <36years. Sixty-eight percent(n=133) of CAD-SCD victims had cardiac symptoms prior to death. This nationwide study found several differences in the pathologic lesions of the heart in victims aged 18-35 and 36-49years, which might be associated with different disease progression leading to death in these age groups. We also report a high frequency of cardiac symptoms prior to death in young CAD-SCD cases, which may enable clinicians to prevent these tragic deaths.


Association of lactate with blood pressure before and after rapid weight loss.
The mechanism linking obesity with its downstream complications is poorly understood. Accumulating evidence suggests that insufficient oxidative capacity plays a central role in the development of insulin resistance and, perhaps, hypertension. To investigate this hypothesis, we measured lactate, a marker of the gap between energy expenditure and oxidative capacity, in 40 obese subjects with the metabolic syndrome (Ob-MS), 40 obese subjects without the metabolic syndrome (Ob), and 20 lean controls (LCs). The 40 Ob-MS participants were then entered into a 12-20 week very low-calorie diet (VLCD) intervention. The change in lactate and a number of other metabolic factors including blood pressure were subsequently assessed. At baseline, median lactate levels were significantly higher in both the Ob (36.4 mg/dl) and Ob-MS (34.7 mg/dl) groups when compared to LCs (17.4 mg/dl; P < 0.001). After the VLCD intervention, Ob-MS subjects lost 14.7 kg on average, corresponding to a 5.0 kg/m(2) decrease in body mass index (BMI). Lactate levels fell from 41.3 to 28.7 mg/dl, a 31% reduction (P = 0.006). Even after adjustment for BMI change, change in lactate was strongly associated with change in diastolic blood pressure (DBP) (P = 0.007) and mean arterial pressure (P = 0.014), but not with systolic blood pressure (SBP) (P = 0.20) or other obesity-related traits. Baseline and longitudinal associations between lactate and DBP suggest that insufficient oxidative capacity may play a role in obesity-related hypertension.


Addressing social barriers and closing the gender knowledge gap: exposure to road shows is associated with more knowledge and more positive beliefs, attitudes and social norms regarding exclusive breastfeeding in rural Zimbabwe.
Exclusive breastfeeding (EBF) is rarely practiced despite its significant child survival benefits. A key constraint to increasing EBF rates in Zimbabwe and most of the developing world is that key decision makers (fathers/partners and other family members) are often poorly informed about EBF and do not attend antenatal clinics where health information is routinely provided. Informed by formative research, a district-wide campaign was conducted in rural Zimbabwe to encourage EBF and expressing and heat treating (EHT) breast milk as a means to maintain EBF. The campaign combined traditional strategies of education, counselling and outreach through health service delivery with a novel road show 'edutainment' intervention to reach men and other community members. A post campaign evaluation measured the association of road show exposure with 20 knowledge items and summative scores of social norms, beliefs and attitudes obtained through exploratory factor analysis. In adjusted models, road show exposure was associated with correct EBF knowledge (β=1.0, 0.001), EHT knowledge (β=1.3, P<0.001) and greater perceived benefits of condom use during pregnancy and breastfeeding (β=0.5, P<0.001), and more positive EBF social norms (β=0.6, P<0.001), EBF beliefs and attitudes (β=1.0, P<0.001) and attitudes towards condom use during breastfeeding (β=0.6, P<0.001). Road show exposure was more strongly associated with EBF knowledge among men (P-value for gender×exposure group interaction=0.03), suggesting that it also closed the knowledge gap between men and women. Longitudinal studies will determine whether road shows were associated with changes in EBF practices.


Effect of professional self-concept on burnout among community health nurses in Chengdu, China: the mediator role of organisational commitment.
To examine the associations among professional self-concept, organisational commitment and burnout, and to analyse the mediating role of organisational commitment on the relationship between professional self-concept and burnout among community health nurses in Chengdu, China. Previous studies have focused on work environmental variables that contributed to burnout in nurses. However, no study has explored the mediating effect of organisational commitment on the correlation between professional self-concept and burnout in community health nurses. A cross-sectional descriptive study. This study was conducted at 36 community health centres in Chengdu, China with 485 nurses sampled using a two-stage sampling method. The measures used in our study included Nurses' Self-concept Questionnaire, Organisational Commitment Scale and Maslach Burnout Inventory. The results of structural equation model techniques indicated that, in the direct approach, positive professional self-concept resulted in increased organisational commitment and reduced burnout. Higher organisational commitment resulted in less burnout. In the indirect approach, organisational commitment performed as a partial mediator on the correlation between professional self-concept and burnout. Positive perception of professional self-concept can result in reduced burnout via enhancing organisational commitment. It is crucial for nursing administrators to develop effective intervention strategies such as skills escalator training and assertive training, and establishing a supportive working environment to enhance nurses' professional self-concept and organisational commitment, and decrease burnout.


CYP3A5 Gene-Guided Tacrolimus Treatment of Living-Donor Egyptian Kidney Transplanted Patients.
Tacrolimus is an approved first-line immunosuppressive agent for kidney transplantations. Part of interindividual and interethnic differences in the response of patients to tacrolimus is attributed to polymorphisms at CYP3A5 metabolic enzyme. CYP3A5 gene expression status is associated with tacrolimus dose requirement in renal transplant recipients. In this study, we determined the allelic frequency of CYP3A5*3 in 76 renal transplanted patients of Egyptian descent. Secondly, we evaluated the influence of the CYP3A5 gene variant on tacrolimus doses required for these patients as well on dose-adjusted tacrolimus trough-concentrations. The CYP3A5*3 variant was the most frequent allele detected at 85.53%. Additionally, our results showed that, mean tacrolimus daily requirements for heterozygous patients (CYP3A5*1/*3) were significantly higher compared to homozygous patients (CYP3A5*3/*3) during the first year after kidney transplantation. This is the first study in Egypt contributing to the individualization of tacrolimus dosing in Egyptian patients, informed by the CYP3A5 genotype.


Use of cancer-specific genomic rearrangements to quantify disease burden in plasma from patients with solid tumors.
Detection of recurrent somatic rearrangements routinely allows monitoring of residual disease burden in leukemias, but is not used for most solid tumors. However, next-generation sequencing now allows rapid identification of patient-specific rearrangements in solid tumors. We mapped genomic rearrangements in three cancers and showed that PCR assays for rearrangements could detect a single copy of the tumor genome in plasma without false positives. Disease status, drug responsiveness, and incipient relapse could be serially assessed. In future, this strategy could be readily established in diagnostic laboratories, with major impact on monitoring of disease status and personalizing treatment of solid tumors.


Hydrodynamics and energy-saving swimming techniques of Pacific bluefin tuna.
Weihs theoretically revealed that during the movement of fish with negative buoyancy, more kinetic energy is saved in the glide and upward (GAU) swimming mode than in the continuous horizontal swimming mode. Because kinetic energy saving depends on dynamic parameters such as the drag and lift of the body, the effects of variations in these parameters on energy saving for different species remain unknown. Here, the kinetic energy saving of Pacific bluefin tuna (PBT), Thunnus orientalis, exhibiting the GAU swimming mode was investigated. The dynamic properties of PBT were estimated by carrying out CFD analysis. The CFD model was produced by using a three-dimensional laser surface profiler, and the model was controlled such that it exhibited swimming motion similar to that of a live PBT swimming in a flume tank. The drag generated by tail beating, which significantly affects the kinetic energy during motion, was twice that generated in the glide mode. The faster the upward swimming speed, the lesser is the kinetic energy saving; therefore, when the upward swimming speed is more than twice the glide speed, there is no gain in the GAU mode. However, when SMR (Standard Metabolic Rate) is considered, if the energy based on SMR is assumed to be 30% of the total energy spent during motion, the most efficient upward swimming speed is 1.4 times the glide speed. The GAU swimming mode of PBT leads to energy saving during motion, and the upward swimming speed and the lift force produced by the pectoral fins for the most efficient drive are unique for different species of different sizes.


The single institutional outcome of postoperative radiotherapy and concurrent chemoradiotherapy in resected non-small cell lung cancer.
This study was conducted to observe the outcomes of postoperative radiotherapy (PORT) with or without concurrent chemotherapy in resected non-small cell lung cancer (NSCLC) in single institution. From 2002 to 2013, 78 patients diagnosed with NSCLC after curative resection were treated with radiotherapy alone (RT, n = 48) or concurrent chemoradiation (CCRT, n = 30). The indications of adjuvant radiation therapy were N2 node positive (n = 31), close or involved resection margin (n = 28), or gross residual disease due to incomplete resection (n = 19). The median radiation dose was 57.6 Gy (range, 29.9 to 66 Gy). Median survival time was 33.7 months (range, 4.4 to 140.3 months). The 5-year overall survival (OS) rate was 49.5% (RT 46% vs. CCRT 55.2%; p = 0.731). The 3-year disease-free survival rate was 45.5% (RT 39.4% vs. CCRT 55.3%; p = 0.130). The 3-year local control rate was 68.1% (RT 64.4% vs. CCRT 77.7%; p = 0.165). The 3-year DMFS rate was 56.1% (RT 52.6% vs. CCRT 61.7%; p = 0.314). In multivariate analysis, age ≥66 years and pathologic stage III were significant poor prognostic factors for OS. Treatment failure occurred in 40 patients. Four patients had radiologically confirmed grade 3 radiation pneumonitis. In NSCLC, adjuvant RT or CCRT after curative surgery is a safe and feasible modality of treatment. OS gain was seen in patients less than 66 years. Postoperative CCRT showed a propensity of achieving better local control and improved disease-free survival compared to RT alone according to our data.


Don't confuse dental soft tissues with odontogenic tumors.
Surgical pathologists are cautioned against the misinterpretation of immature dental tissues (dental papillae and follicles) and dental pulp as odontogenic tumors, especially odontogenic myxomas and fibromas. The close histologic similarity of the immature tissues to tumors may require a clinical-radiologic correlation with the histopathologic specimen in order to distinguish the locally aggressive tumors from innocuous dental tissues.


Propagation of fluorescent viruses in growing plaques.
To study virus propagation, we have developed a method by which the propagation of the Lambda bacteriophage can be observed and quantified. This is done by creating a fusion protein of the capsid protein gpD and the enhanced yellow fluorescent protein (EYFP). We show that this fusion allows capsid formation and that the modified viruses propagate on a surface covered with host bacteria thus forming fluorescent plaques. The intensity of fluorescence in a growing plaque determines the distribution of phages. This provides a new tool to study the propagation of infection at the microscopic level.


Nuclear inositide specific phospholipase C signalling - interactions and activity.
Evidence accumulated over the past 20 years has highlighted the presence of an autonomous nuclear inositol lipid metabolism, and suggests that lipid signalling molecules are important components of signalling pathways operating within the nucleus. Nuclear polyphosphoinositide (PI) signalling relies on the synthesis and metabolism of phosphatidylinositol 4,5-bisphosphate, which can modulate the activity of effector proteins and is a substrate of signalling enzymes. The regulation of the nuclear PI pool is totally independent from the plasma membrane counterpart, suggesting that the nucleus constitutes a functionally distinct compartment of inositol lipids metabolism. Among the nuclear enzymes involved in PI metabolism, inositide specific phospholipase C (PI-PLC) has been one of the most extensively studied. Several isoforms of PI-PLCs have been identified in the nucleus, namely PI-PLC-β1, γ1, δ1 and ζ; however, the β1 isozyme is the best characterized. In the present review, we focus on the signal transduction-related metabolism of nuclear PI-PLC and review the most convincing evidence for PI-PLC expression and activity being involved in differentiation and proliferation programmes in several cell systems. Moreover, nuclear PI-PLC is an intermediate effector and interactor for nuclear inositide signalling. The inositide cycle exists and shows a biological role inside the nucleus. It is an autonomous lipid-dependent signalling system, independently regulated with respect to the one at the plasma membrane counterpart, and is involved in cell cycle progression and differentiation.


[Analysis of poisonous trace elements in huangwu gongmitai].
A comparative study was made on the dissolved amount of poisonous trace elements mercury and arsenic contained in hydrargyri subchloridum and realgar of gynecological suppository in artificially simulated vaginal acid-base liquid with that contained in hydrargyri subchloridum and realgar in artificial gastric juice stipulated in Pharmacopeia of China. The result shows that the dissolved amount of mercury and arsenic contained in the suppository is much smaller than that stipulated in Pharmacopeia for oral administration.