[Acute adrenal insufficiency during unilateral adrenal hemorrhage secondary to the antiphospholipid syndrome].
Acute adrenal insufficiency during antiphospholipid syndrome is usually due to a bilateral adrenal hemorrhage. For a patient, an unilateral involvement has induced an acute adrenal insufficiency. A patient with an antiphospholipid syndrome has developed an acute adrenal insufficiency with an unilateral adrenal hemorrhage. This complication was caused by a concurrent steroid therapy, for an associated lupus, which resulted in a suppression of the contralateral adrenal gland. In patients with antiphospholipid syndrome and concurrent steroid therapy, usually for lupus, unilateral adrenal hemorrhage can cause acute adrenal insufficiency. Withdrawal of steroid might be difficult in case of undetected bilateral hemorrhage.


Natriuretic peptide expression in the heart of the TTR-ANP transgenic mouse-Comparison to the normal heart.
The transgenic mice, TTR-ANP, carrying a fusion gene comprising the transthyretin promoter and the atrial natriuretic peptide (ANP) structural sequence, are known to have elevated ANP plasma levels as well as lowered blood pressure levels. On the other hand, it is not known whether these transgenic mice show changed natriuretic peptide (NP) expression patterns in the heart. Therefore, we examined the distribution of NPs in the myocardium and the conduction system of transgenic mice overexpressing ANP, as well as in wild-type littermates. The hearts were serially sectioned and processed for immunohistochemistry, with antisera against ANP and brain natriuretic peptide (BNP). Florescence microscopy was performed for qualitative analysis. Immunoreactivity for ANP and BNP was detected to a similar degree in the conduction system of both transgenic and wild-type mice. The nodal tissues never exhibited immunoreactions for ANP or BNP, whereas Purkinje fibers of the atrioventricular junctional tissue, bundle branches, and the peripheral Purkinje fiber network exhibited specific immunoreactivity. Atrial and ventricular myocytes of both transgenic and wild-type mice exhibited ANP and BNP to a similar extent. This is the first study examining the expression pattern of NPs in the cardiac conduction system of the mouse as well as the pattern of ANP and BNP expression in the conduction system of TTR-ANP transgenic mice and its wild-type siblings. The findings in this study suggest that ectopic ANP expression and release do not repress cardiac production of ANP.


[A proposal to convert our view from precision into accuracy in routine analysis].
Recently, measurement systems in clinical chemistry have been improved to be more precise in analysis than those in 1980s. As a result, several advances in instruments and reagents have been brought such as incorporating microprocessors into hardwares of instruments and developing ready-to-use reagents, and the precision level of measurement systems is now sufficient for routine analysis. In the near future, however, we will have to focus on the accuracy of measurement systems to obtain accurate and commutable laboratory data. We report a present status of the precision in routine analysis and our activity in data maintenance for accurate analysis by reference methods.


[Integrated quality assurance].
The definition of terms and connotation of "Quality", "Quality Assurance" and "Integration" lead to an analysis and understanding of inhibiting and fostering factors of the "Health Triad" of people, animals and environment. Although "Quality" is largely or ultimately determined by the consumer, there are considerable differences as this term is applied by (a) the individual consumer, (b) the dynamic producer defending or gaining markets, (c) those engaged in traditional product manufacturing, or (d) governments setting (minimum) requirements for the sake of free trade. "Quality Assurance" offers cooperation of partners all along the food chain from "pasture to table". The managerial process turned into a continuum of responsibility and agreement on processes and product characteristics. This overcomes the disadvantages of strategies stressing distinct defense barriers. In practice this philosophy of a predominant role of defence barriers proved largely partnership destructive, in that it permitted to shift responsibilities for failures and to claim administrative competence according to momentary situations and interests. "Integrated Quality Assurance" means mutual agreement of two or more partners along the food chain (e. g. feed producers, farmers, animal health industry, veterinarians and food processors) on product characteristics and production methods. It involves essential system elements including facilities, materials, manpower, information, transport, management etc. Different principles and procedures of quality assurance have been introduced in practice, including agriculture and food processing. These different approaches are not mutually exclusive but largely of complementary nature.(ABSTRACT TRUNCATED AT 250 WORDS)


Neural specializations for speech and pitch: moving beyond the dichotomies.
The idea that speech processing relies on unique, encapsulated, domain-specific mechanisms has been around for some time. Another well-known idea, often espoused as being in opposition to the first proposal, is that processing of speech sounds entails general-purpose neural mechanisms sensitive to the acoustic features that are present in speech. Here, we suggest that these dichotomous views need not be mutually exclusive. Specifically, there is now extensive evidence that spectral and temporal acoustical properties predict the relative specialization of right and left auditory cortices, and that this is a parsimonious way to account not only for the processing of speech sounds, but also for non-speech sounds such as musical tones. We also point out that there is equally compelling evidence that neural responses elicited by speech sounds can differ depending on more abstract, linguistically relevant properties of a stimulus (such as whether it forms part of one's language or not). Tonal languages provide a particularly valuable window to understand the interplay between these processes. The key to reconciling these phenomena probably lies in understanding the interactions between afferent pathways that carry stimulus information, with top-down processing mechanisms that modulate these processes. Although we are still far from the point of having a complete picture, we argue that moving forward will require us to abandon the dichotomy argument in favour of a more integrated approach.


Sperm-associated antigen 5 is a potential biomarker for poor prognosis in breast cancer.
Sperm-associated antigen 5 (SPAG5) is currently considered to serve a role in promoting tumor cell growth and is overexpressed in several types of human cancer. However, to the best of our knowledge, the association of SPAG5 with molecular subtypes of patients with breast cancer (BC) remains to be fully investigated. Reverse transcription-quantitative polymerase chain reaction and immunohistochemistry on tissue microarrays were used in the current study to detect the expression levels of SPAG5 mRNA and protein, respectively, in BC. The association between SPAG5 mRNA and protein levels, and clinical characteristics and prognostic information were investigated. SPAG5 mRNA and protein levels were identified to be higher in BC tissues compared with matched adjacent nontumor tissues. High expression level of SPAG5 protein was associated with tumor size, histological grade, estrogen receptor expression, Ki-67 expression, lymph node status, tumor-node-metastasis (TNM) stage and the triple-negative BC subtype. In addition, high expression level of SPAG5 protein was associated with a poor prognosis in patients with BC. In summary, the current study suggests that SPAG5 is a novel and useful prognostic biomarker in BC.


apoE isoform-specific disruption of amyloid beta peptide clearance from mouse brain.
Neurotoxic amyloid beta peptide (Abeta) accumulates in the brains of individuals with Alzheimer disease (AD). The APOE4 allele is a major risk factor for sporadic AD and has been associated with increased brain parenchymal and vascular amyloid burden. How apoE isoforms influence Abeta accumulation in the brain has, however, remained unclear. Here, we have shown that apoE disrupts Abeta clearance across the mouse blood-brain barrier (BBB) in an isoform-specific manner (specifically, apoE4 had a greater disruptive effect than either apoE3 or apoE2). Abeta binding to apoE4 redirected the rapid clearance of free Abeta40/42 from the LDL receptor-related protein 1 (LRP1) to the VLDL receptor (VLDLR), which internalized apoE4 and Abeta-apoE4 complexes at the BBB more slowly than LRP1. In contrast, apoE2 and apoE3 as well as Abeta-apoE2 and Abeta-apoE3 complexes were cleared at the BBB via both VLDLR and LRP1 at a substantially faster rate than Abeta-apoE4 complexes. Astrocyte-secreted lipo-apoE2, lipo-apoE3, and lipo-apoE4 as well as their complexes with Abeta were cleared at the BBB by mechanisms similar to those of their respective lipid-poor isoforms but at 2- to 3-fold slower rates. Thus, apoE isoforms differentially regulate Abeta clearance from the brain, and this might contribute to the effects of APOE genotype on the disease process in both individuals with AD and animal models of AD.


Utilization of plant-derived recombinant human β-defensins (hBD-1 and hBD-2) for averting salmonellosis.
We describe the use of plant-made β-defensins as effective antimicrobial substances for controlling salmonellosis, a deadly infection caused by Salmonella typhimurium (referred to further as S. typhi). Human β-defensin-1 (hBD-1) and -2 (hBD-2) were expressed under the control of strong constitutive promoters in tobacco plants, and bio-active β-defensins were successfully extracted. In the in vitro studies, enriched recombinant plant-derived human β-defensin-1 (phBD-1) and -2 (phBD-2) obtained from both T1 and T2 transgenic plants showed significant antimicrobial activity against Escherichia coli and S. typhi when used individually and in various combinations. The 2:1 peptide combination of phBD-1:phBD-2 with peptides isolated from T1-and T2-generation plants reduced the growth of S. typhi by 96 and 85 %, respectively. In vivo studies employing the mouse model (Balb/c) of Salmonella infection clearly demonstrated that the administration of plant-derived defensins individually and in different combinations enhanced the mean survival time of Salmonella-infected animals. When treatment consisted of the 2:1 phBD-1:phBD-2 combination, approximately 50 % of the infected mice were still alive at 206 h post-inoculation; the lowest number of viable S. typhi was observed in the liver and spleen of infected animals. We conclude that plant-made recombinant β-defensins (phBD-1 and phBD-2) are promising antimicrobial substances and have the potential to become additional tools against salmonellosis, particularly when used in combination.


Effect of hyperthermia on the radiosensitivity of normal and malignant cells in mice.
The effect of systemic hyperthermia on the in vivo radiation response of normal and malignant mouse cells was evaluated. X-irradiation of L1210 cells and Ehrlich ascites cells at body temperatures above 41 degrees C resulted in strongly enhanced tumor cell death. The magnitude of this thermal effect increased with increasing temperatures. Hypoxic tumor cells were particularly sensitive to combined heat-radiation treatment. L1210 leukemia cells did not become resistant to the sensitizing effects of hyperthermia even after repeated heat exposures over several transplant generations. The sensitizing action of hyperthermia varied with different heating strategies. Heating before or during irradiation did not materially alter the radiation response of tumor cells. Maximal potentiation of radiation damage was achieved only when the tumorous mice were subjected to at least 20 minutes heat incubation after irradiation. LD studies on ICR mice revealed that moderate hyperthermia (41.5 degrees C) does not alter the radiation response of normal body tissues. These findings indicate that it is possible to devise hyperthermic treatment regimens that drastically enhance radiation-induced tumor cell death in vivo without reducing the radioresistance of normal tissues.


Glass-ceramic optical fiber containing Ba2TiSi2O8 nanocrystals for frequency conversion of lasers.
A glass-ceramic optical fiber containing Ba2TiSi2O8 nanocrystals fabricated using a novel combination of the melt-in-tube method and successive heat treatment is reported for the first time. For the melt-in-tube method, fibers act as a precursor at the drawing temperature for which the cladding glass is softened while the core glass is melted. It is demonstrated experimentally that following heat treatment, Ba2TiSi2O8 nanocrystals with diameters below 10 nm are evenly distributed throughout the fiber core. Comparing to the conventional rod-in-tube method, the melt-in-tube method is superior in terms of controllability of crystallization to allow for the fabrication of low loss glass-ceramic fibers. When irradiated using a 1030 nm femtosecond laser, an enhanced green emission at a wavelength of 515 nm is observed in the glass-ceramic fiber, which demonstrates second harmonic generation of a laser action in the fabricated glass-ceramic fibers. Therefore, this new glass-ceramic fiber not only provides a highly promising development for frequency conversion of lasers in all optical fiber based networks, but the melt-in-tube fabrication method also offers excellent opportunities for fabricating a wide range of novel glass-ceramic optical fibers for multiple future applications including fiber telecommunications and lasers.


Electrophysiological correlates of spontaneous mind wandering in attention-deficit/hyperactivity disorder.
We recently hypothesised that increased spontaneous mind wandering (MW-S) reflects a core process underlying attention-deficit/hyperactivity disorder (ADHD). Previous studies show that individuals with ADHD and neurotypical individuals with increased MW-S display similar cognitive-performance and electrophysiological (EEG) impairments in attentional processes. However, the cognitive-EEG markers associated with increased MW-S in ADHD remain poorly understood. We therefore investigated such markers in a sample of 69 sex- and age-matched adults with ADHD and 29 controls during the Sustained Attention to Response Task. We compared task performance and EEG measures (P3, time-frequency brain-oscillations) of attentional processes between groups, and examined their association with a validated self-report questionnaire of MW-S. Finally, we tested the hypothesis that MW-S and ADHD diagnosis relate to the same cognitive-EEG impairments using a hierarchical regression model. Compared to controls, adults with ADHD showed attenuations in P3, event-related alpha and beta suppression during response inhibition (No-Go trials), and theta power activations during response execution (Go trials), as well as increased reaction time variability and more commission/omission errors. MW-S was also continuously associated with most cognitive-EEG measures related to ADHD. The hierarchical regressions on measures associated with both ADHD diagnosis and MW-S showed that MW-S did not explain additional variance in the cognitive-EEG markers (except for beta suppression) beyond ADHD diagnosis, and vice versa. These findings are consistent with our hypothesis that ADHD diagnosis and MW-S share common neural deficits, and that MW-S may reflect a core symptom of the disorder.


Bacteriuria localization and response to single-dose therapy in women.
One hundred women with bacteriuria had the infection localized by the "bladder-washout" technique. Thirty-six of the 39 with infection confined to the bladder were cured with a single intramuscular injection of 500 mg of kanamycin sulfate, whereas 47 of the 65 patients with infection originating from their upper tract relapsed almost immediately. None of the seven patients with abnormal pyelograms and associated upper tract infection was cured with kanamycin. These results suport the hypothesis that bladder infections in women can be readily cured with a very short course of therapy. Women who relapse after a single injection of kanamycin almost always have renal infection.


Structure and content of diaries written by close relatives for intensive care unit patients: A narrative approach (DRIP study).
To investigate structure and content of a nurse prompted diary written by relatives for intensive care unit (ICU) patients. A narrative analysis of ICU diaries. From September 2015-August 2016, 12 diaries authored by 12 relatives for 12 ICU patients were sampled at 3-4 months post-ICU discharge. We used Ricoeur's hermeneutical phenomenology as a framework for a narrative analysis of the diaries. The first step was naïve reading, followed by structural analysis exploring the internal relations of the text. The structural analysis was broadened by exploring narrative structures. The last step was critical interpretation of the findings. The diaries had a clear narrative structure; the diary-timeline consisted of: Pre-ICU phase, Early ICU phase, Culmination, Recovery and Post-ICU reflection. Three themes described the content of the diary: Struggling to get the story right for the patient; striving to understand what was happening and longing to re-establish a connection with the patient. Keeping a diary was perceived by the relatives as a challenging but rewarding task. The diary had the potential for reflection and a deeper understanding of the ICU stay. The diary served as a locus for patient and relatives to connect or re-connect, but some diaries might be too personal and emotional to share with the patient. Future research needs to explore advantages and disadvantages of ICU diaries authored by relatives.


Effect of nanostructure on the properties of water at the water-hydrophobic interface: a molecular dynamics simulation.
The local structure of water near hydrophobic surfaces of different surface topographies has been analyzed by molecular dynamics simulation. An alkane crystal has been taken as the parent model for a hydrophobic surface. Surface structures were created by placing pits into it, which were half a nanometer deep and several nanometers wide. Around all structures, the water has a lower density, less orientational ordering, fewer water-water hydrogen bonds, and fewer surface contacts than for a flat unstructured surface. This indicates that the structured surfaces are more hydrophobic than the flat surface. Of the structures investigated, pits with a diameter of approximately 2.5 nm were effective in increasing the hydrophobic character of the surface.


Understanding the Optimal Cooperativity of Human Glucokinase: Kinetic Resonance in Nonequilibrium Conformational Fluctuations.
The cooperativity of a monomeric enzyme arises from dynamic correlation instead of spatial correlation and is a consequence of nonequilibrium conformation fluctuations. We investigate the conformation-modulated kinetics of human glucokinase, a monomeric enzyme with important physiological functions, using a five-state kinetic model. We derive the non-Michealis-Menten (MM) correction term of the activity (i.e., turnover rate), predict its relationship to cooperativity, and reveal the violation of conformational detailed balance. Most importantly, we reproduce and explain the observed resonance effect in human glucokinase (i.e., maximal cooperativity when the conformational fluctuation rate is comparable to the catalytic rate). With the realistic parameters, our theoretical results are in quantitative agreement with the reported measurement by Miller and co-workers. The analysis can be extended to a general chemical network beyond the five-state model, suggesting the generality of kinetic cooperativity and resonance.


Efficient equilibrium sampling of all-atom peptides using library-based Monte Carlo.
We applied our previously developed library-based Monte Carlo (LBMC) to equilibrium sampling of several implicitly solvated all-atom peptides. LBMC can perform equilibrium sampling of molecules using precalculated statistical libraries of molecular-fragment configurations and energies. For this study, we employed residue-based fragments distributed according to the Boltzmann factor of the optimized potential for liquid simulations all-atom (OPLS-AA) forcefield describing the individual fragments. Two solvent models were employed: a simple uniform dielectric and the generalized Born/surface area (GBSA) model. The efficiency of LBMC was compared to standard Langevin dynamics (LD) using three different statistical tools. The statistical analyses indicate that LBMC is more than 100 times faster than LD not only for the simple solvent model but also for GBSA.


Cyclooxygenase Inhibitors as a New Therapeutic Strategy in Small Bowel Transplantation.
The long-term outcome of intestinal transplantations is still not favorable, which is partly due to the intestinal susceptibility to ischemia. There are several indications that the inflammatory response to ischemia-reperfusion injury is mediated by cyclooxygenases and that their inhibition may be associated with improved organ function. The aim of this study was to analyze if cyclooxygenase (COX) inhibitors could improve the early posttransplant outcome after orthotopic small bowel transplantation. Small bowel transplantation was performed between rats to test the impact of nonselective (Piroxicam), preferential (Meloxicam), and selective COX-2 inhibitors (Parecoxib). The donor intestines were either perfused and stored with inhibitor or had inhibitor administered intravenously after transplantation. Using COX inhibitors, a sequential increase of posttransplantation intestinal integrity could be shown, with Parecoxib the least effective and Meloxicam the most effective treatment. These differences were in line with the downregulation of COX-2 activity by the inhibitors. Functionally, the same tendency could be seen in diminished expression of proinflammatory molecules, decreased leucocyte inflammation, and significantly improved graft microcirculation. In most cases, the intravenous administration was more effective. However, the COX inhibitors used were shown to cause relevant hepatotoxicity under nearly all conditions, but particularly under intravenous administration. Only Meloxicam in histidine-tryptophan-ketoglutarate was demonstrated to be a safe drug without hepatotoxic side effects. The activity of COX contributes to ischemia-reperfusion injury after intestinal transplantation. In this comparative study, the administration of the preferential COX-2 inhibitor Meloxicam via histidine-tryptophan-ketoglutarate showed the best graft-protective attributes and the lowest hepatotoxic side effects.


[Revealing of the role of NO in the pathogenesis of hypothyroidism].
There have been studied changes in blood and tissue NO levels and its correction in rats exposed to thyrectomy. NO levels were measured by the method of EPR using spin-trap sodium diethyldithiocarbamat. In 22 hours after thyrectomy contents of free nitric oxide in myocardium and liver tissues increased by 33% and 43,3% respectively. At the same time, intensive EPR signals of nitrosyl complexes of non-heme iron (FeSNO, g=2,03) were registered in EPR spectra of liver and myocardium tissues, at that free nitric oxide levels in blood of animals significantly decreased. In conclusion, NO-dependent signal system plays important role in the regulation of redox-homeostasis at hypothyroidism; long-term inadequate activation of NO synthesis may cause intensification of body oxidative stress, which in turn results in oxidative degradation of vasoactive nitric oxide, disturbance of blood vessel reactivity, alteration of tissue blood and oxygen supply, that in turn facilitate farther aggravation of oxidative metabolism disorder and the development of irreversible alterations in tissues. In case of treatment with L-thyroxin or L-thyroxin + oligocrin oxidative metabolism markers and content of NO in blood and tissues normalize, at that oligocrin enhances thyroxin efficacy. Thus, based on the obtained results of the conducted research we suggest that application of pharmaceutical preparations with antioxidant activity along with specific hormonal therapy is appropriate for treatment of hypothyroidism.


Systemic interferon alpha 2b treatment in Behçet's syndrome.
To test the efficacy of systemic interferon alpha 2b (IFN alpha 2b) treatment in the mucocutaneous and joint symptoms of Behçet's syndrome. The 48-week open, self-controlled trial was conducted in 3 phases. After the pretreatment phase of 16 weeks, 20 patients (8 men, 12 women; mean age 37 +/- 7 years SD) were treated with IFN-alpha 2b at a dose of 5 million units 3 times a week for 6 weeks followed by 5 million units once a week for 10 weeks. The subsequent 16 weeks not taking the medication was the posttreatment phase. Treatment with IFN-alpha 2b significantly reduced the mean number of arthritis attacks (F = 3.48; p < 0.05), their mean duration (F = 3.77; p < 0.05), and the mean erythrocyte sedimentation rate (F = 6.66; p < 0.001). The mean number of mucocutaneous lesions also showed a decrease, but this was not statistically significant. Except for the duration of arthritis, the mean number and frequency of all symptoms tended to return to pretreatment levels in the posttreatment phase. This pilot study shows that systemic IFN may be effective in the treatment of arthritis of Behçet's syndrome.


Nocardia rubra cell-wall skeleton activates an immune response in cervical tissue via stimulating FPR3 to enhance dendritic cell-mediated Th1 differentiation.
Nocardia rubra cell wall skeleton (Nr-CWS) has proven to be a successful medicine for therapy of cervical human papillomavirus infection. The mechanism of action of Nr-CWS is unclear but may involve a stimulatory effect on the host immune system. We previously found that CD4+ T cells were increased in cervical tissue after Nr-CWS treatment. Microarray data from these cervical tissues revealed the significant upregulation of formylated peptide receptor 3 (FPR3). This study aimed to explore the role of Nr-CWS in immunomodulatory based on these findings. Examination of CD4+ T cell subsets in cervical tissue from patients who received Nr-CWS revealed substantial increases in Th1 cytokines and transcription factors. The regulatory effects of Nr-CWS on the function and phenotype of dendritic cells (DCs) were assessed in comparison with the traditional DC maturation inducer lipopolysaccharide (LPS). Similar to LPS, Nr-CWS potently induced DC maturation and interleukin-12 (IL-12) secretion. Differentiation of T cells induced by Nr-CWS stimulated DCs was assessed using the mixed lymphocyte reaction assay. Significant differentiation towards Th1 was evident. Finally, FPR3 expression in DCs in response to Nr-CWS and LPS was measured. Nr-CWS potently upregulated FPR3 expression, while the LPS did not. Silencing FPR3 in DCs reduced Nr-CWS-induced IL-12 production and Th1 cell polarization in co-cultured T cells. The collective findings indicate that Nr-CWS may target FPR3 on the surface of DC cells and activate a Th1-type immune response. The findings clarify the basis of the antiviral immune effects of Nr-CWS on human papillomavirus.


Proenkephalin mediates the enduring effects of adolescent cannabis exposure associated with adult opiate vulnerability.
Marijuana use by teenagers often predates the use of harder drugs, but the neurobiological underpinnings of such vulnerability are unknown. Animal studies suggest enhanced heroin self-administration (SA) and dysregulation of the endogenous opioid system in the nucleus accumbens shell (NAcsh) of adults following adolescent Δ(9)-tetrahydrocannabinol (THC) exposure. However, a causal link between proenkephalin (Penk) expression and vulnerability to heroin has yet to be established. To investigate the functional significance of NAcsh Penk tone, selective viral-mediated knockdown and overexpression of Penk was performed, followed by analysis of subsequent heroin SA behavior. To determine whether adolescent THC exposure was associated with chromatin alteration, we analyzed levels of histone H3 methylation in the NAcsh via chromatin immunoprecipitation at five sites flanking the Penk gene transcription start site. Here we show that regulation of the Penk opioid neuropeptide gene in NAcsh directly regulates heroin SA behavior. Selective viral-mediated knockdown of Penk in striatopallidal neurons attenuates heroin SA in adolescent THC-exposed rats, whereas Penk overexpression potentiates heroin SA in THC-naïve rats. Furthermore, we report that adolescent THC exposure mediates Penk upregulation through reduction of histone H3 lysine 9 (H3K9) methylation in the NAcsh, thereby disrupting the normal developmental pattern of H3K9 methylation. These data establish a direct association between THC-induced NAcsh Penk upregulation and heroin SA and indicate that epigenetic dysregulation of Penk underlies the long-term effects of THC.


Impact of Elimination or Reduction of Dietary Animal Proteins on Cancer Progression and Survival: Protocol of an Online Pilot Cohort Study.
Current evidence suggests that the incidence of cancer is low in vegan populations, and experimental studies have revealed a significant role of dietary proteins in cancer development and progression. However, little data currently exists regarding the effect of a plant-based diet on the progression of diagnosed cancer. The main objective of this study is to determine if a reduction or total elimination of animal protein from the diet can positively influence the outcome of an existing cancer and, in addition to standard oncological therapies, increase remission rates. The primary aim of this online study is to test the effect on remission rates in cancer patients (primary outcome) with distinct self-selected dietary patterns (omnivore, lacto-ovo-vegetarian, vegan), and allow for an estimation of the effect size. Secondary outcomes are tumor behavior, relapse-free interval, therapies, therapy tolerability and side-effects, comorbidities, medication, quality of life, acceptance, and feasibility of the selected diet. Safety concerns exist for vegan diets (especially in cancer patients) and the study will carefully monitor for deterioration of health, tumor progression, or malnutrition. Furthermore, the study will evaluate the online portal as a study platform (technical and safety aspects, and sequence of displayed questionnaires) as well as the validity of self-reported and online-generated data. The study was performed between April, 2015 and June, 2016, and a preliminary evaluation of safety aspects was undertaken after June, 2016. Primary and secondary outcomes will be evaluated when the final patients complete the study in December, 2016. This study will reveal information about the effects of dietary patterns on cancer disease and progression. The methodology of the study addresses several aspects and limitations of nutrition studies in cancer patients, such as precision of nutrition data, acceptance criteria, online methodology, and safety aspects. Clinicaltrials.gov NCT02437474; https://clinicaltrials.gov/ct2/show/NCT02437474 (Archived by WebCite at http://www.webcitation.org/6jL7UUCVq).


Plasmonic Vertically Coupled Complementary Antennas for Dual-Mode Infrared Molecule Sensing.
Here we report an infrared plasmonic nanosensor for label-free, sensitive, specific, and quantitative identification of nanometer-sized molecules. The device design is based on vertically coupled complementary antennas (VCCAs) with densely patterned hot-spots. The elevated metallic nanobars and complementary nanoslits in the substrate strongly couple at vertical nanogaps between them, resulting in dual-mode sensing dependent on the light polarization parallel or perpendicular to the nanobars. We demonstrate experimentally that a monolayer of octadecanethiol (ODT) molecules (thickness 2.5 nm) leads to significant antenna resonance wavelength shift over 136 nm in the parallel mode, corresponding to 7.5 nm for each carbon atom in the molecular chain or 54 nm for each nanometer in analyte thickness. Additionally, all four characteristic vibrational fingerprint signals, including the weak CH3 modes, are clearly delineated experimentally in both sensing modes. Such a dual-mode sensing with a broad wavelength design range (2.5 to 4.5 μm) is potentially useful for multianalyte detection. Additionally, we create a mathematical algorithm to design gold nanoparticles on VCCA sensors in simulation with their morphologies statistically identical to those in experiments and systematically investigate the impact of the nanoparticle morphology on the nanosensor performance. The nanoparticles form dense hot-spots, promote molecular adsorption, enhance near-field intensity 103 to 104 times, and improve ODT refractometric and fingerprint sensitivities. Our VCCA sensor structure offers a great design flexibility, dual-mode operation, and high detection sensitivity, making it feasible for broad applications from biomarker detection to environment monitoring and energy harvesting.


Effect of different decellularization protocols on reendothelialization with human cells for a perfused renal bioscaffold of the rat.
Scaffolds for tissue engineering can be received by whole organ decellularization while maintaining the site-specific extracellular matrix and the vascular tree. One among other decellularization techniques is the perfusion-based method using specific agents e.g. SDS for the elimination of cellular components. While SDS can disrupt the composition of the extracellular matrix and impair the adherence and growth of site-specific cells there are indications that xenogeneic cell types may benefit from protein denaturation by using higher detergent concentrations. The aim of this work is to investigate the effect of two different SDS-concentrations (i.e. 0.66% and 3%) on the ability of human endothelial cells to adhere and proliferate in an acellular rat kidney scaffold. Acellular rat kidney scaffold was obtained by perfusion-based decellularization through the renal artery using a standardized protocol including SDS at concentrations of 0.66% or 3%. Subsequently cell seeding was performed with human immortalized endothelial cells EA.hy 926 via the renal artery. Recellularized kidneys were harvested after five days of pressure-controlled dynamic culture followed sectioning, histochemical and immunohistochemical staining as well as semiquantitative analysis. Efficacy of decellularization was verified by absence of cellular components as well as preservation of ultrastructure and adhesive proteins of the extracellular matrix. In semiquantitative analysis of recellularization, cell count after five days of dynamic culture more than doubled when using the gentle decellularization protocol with a concentration of SDS at 0.66% compared to 3%. Detectable cells maintained their endothelial phenotype and presented proliferative behavior while only a negligible fraction underwent apoptosis. Recellularization of acellular kidney scaffold with endothelial cells EA.hy 926 seeded through the renal artery benefits from gentle decellularization procedure. Because of that, decellularization with a SDS concentration at 0.66% should be preferred in further studies and coculture experiments.


Altered wing phenotypes of captive-bred migratory birds lower post-release fitness.
Captive breeding and release to the wild is a globally important conservation tool. However, captivity can result in phenotypic changes that incur post-release fitness costs, especially if they affect strenuous or risky behaviours. Bird wing shape is critical for migration success and suboptimal phenotypes are strongly selected against. In this study, I demonstrate surprising plasticity of bird wing phenotypes in captivity for 4/16 studied species. In a model species, captive-born juveniles with wild wing phenotypes (a 1-mm longer distal primary flight feather) survived post-release at 2.7 times the rate of those with captive phenotypes (i.e. a shorter distal feather). Subtle phenotypic changes and their fitness impacts are more common than widely realised because they are easily overlooked. To improve captive breeding for conservation, practitioners must surveil phenotypic changes and find ways to mitigate them.


A comparison of the use of sedatives in a hospital support team and in a hospice.
This study examines how frequently and for what indications sedatives are prescribed in a hospital support team and in a hospice. We also looked at the survival of sedated patients from the date of admission and from the start of sedation. Overall 26% of patients were prescribed sedatives in order to sedate them (31% at the hospice and 21% at the hospital) and 43% of patients were given sedatives for symptom control (67% at the hospice and 21% at the hospital). Sedated patients survived for a mean of 1.3 days after the start of sedation, and there was no detectable difference in survival from the date of admission between sedated and nonsedated patients.


[New horizons in the treatment of atopic dermatitis].
Nearly fifty years after their introduction, corticoids continue to be one of the main pillars of dermatological therapy in general and in atopic dermatitis in particular. However, their use is limited by local and systemic adverse effects.There is enormous demand for anti-inflammatory agents not belonging to the corticoid group that would be useful in the different inflammatory dermatoses.In the last few years the therapeutic arsenal for atopic dermatitis has increased with two distinct groups of drugs: topical immunomodulators and leukotriene inhibitors. Both groups of drugs are new and new compounds belonging to these types of drugs will probably appear in the next few years.Among the alternatives to corticoids are the immunomodulators and the most promising of these are macrolide antibiotics. Tacrolimus (FK 506) and pimecrolimus (ASM 981) belong to this group of substances with a high capacity to inhibit T lymphocyte activation. Although they also act on other cells playing a role in atopic dermatitis (mastocytes, Langerhans' cells, B lymphocytes) their action on T lymphocytes seems to be the most important. In T lymphocytes, these drugs act by inhibiting the action of calmodulin, a vital enzyme in the activation chain of these cells that ends in the production of interleukin 2 and other proinflammatory cytokines.The accumulated evidence of the various publications seems to indicate that tacrolimus is a safe and effective treatment of atopic dermatitis in patients aged 2 years or more. The drug was approved for clinical use 3 years ago in Japan and more than 1 year ago in the United States. The number of randomized clinical trials comparing this drug with placebo or various corticoids demonstrate that its action is overwhelming. Its anti-inflammatory action is similar to that of high-potency topical corticoids. Two doses daily are required and the drug has been tested in patients with moderate-to-severe atopic dermatitis. Published data from more than 10,000 patients guarantee its safety. The most frequent short-term adverse effect is a burning sensation in the site of application lasting a few minutes.Pimecrolimus has not yet been commercialized in any country and is currently undergoing phase III clinical investigations. It has been tested in three clinical trials in patients aged more than 3 months old with mild-moderate atopic dermatitis. Its safety profile is good and similar to that of tacrolimus.The number and quality of the data provided by studies of treatment with leukotriene inhibitors (zafirlukast, montelukast and zileuton) is much lower but these substances seem to warrant further investigation. Only five small series undergoing treatment with these products have been published.


Prenatal Maternal Occupational Exposure and Postnatal Child Exposure to Elemental Mercury.
Young children are highly vulnerable to elemental mercury toxicity, and elementary mercury exposure in young children in China unfortunately occurs regularly because of the wide use of fluorescent lamps, glass thermometers, and other mercury-contained items. This study aimed to summarize such recent cases in a referral clinic and to make recommendations for postexposure treatment and prevention of future exposure. Patients were evaluated between January 2007 and December 2009 in environmental health facilities throughout China and were referred to our clinic. A total of 6 children younger than 4 years with significant elemental mercury exposure were included in this case series analysis. The total mercury content in blood and hair (fetal hair if necessary) and average 24-hour urine mercury concentrations were analyzed. Meso-2,3-dimercaptosuccinic acid or surgery was prescribed for the patient if necessary. Young children were found to be exposed in 3 ways as follows: prenatal exposure through maternal occupational contact in compact fluorescent-lamp factories (2 cases), broken thermometers (3 cases), and other causes of accidental inhalation of mercury vapor during the embryonic and lactation periods (1 case). For 3 cases caused by broken thermometers, x-ray images helped to identify the position of mercury residues. Local excision was used to remove mercury from the floor of the mouth in 1 case. One child was prescribed oral meso-2,3-dimercaptosuccinic acid, and a good response was received. Substitution of mercury-in-glass thermometers and vigilance to prevent women of childbearing age from occupational mercury exposure were suggested. Treatment selection should vary according to patient situations.


Rituximab, MS, and pregnancy.
To describe the safety and efficacy of rituximab (RTX) in MS and pregnancy, we conducted a retrospective cohort study of 74 pregnancies among 55 women treated with RTX for MS and their offspring. We used prospectively collected information from the electronic health record at Kaiser Permanente Southern California between 2012 and 2019 of mother and baby to identify treatment history, pregnancy outcomes, and relapses. Last RTX exposure before conception occurred between 1.8 and 5.2 months in 32 (49%) of 65 pregnancies and accidentally during the first trimester in 9 (12%). Among 38 live births, adverse pregnancy outcomes were as follows: 3 preterm deliveries (including 1 set of twins), 1 neonatal death (preterm twin), and 1 perinatal stroke (full-term). No stillbirths, chorioamnionitis, or major malformations were found. Fifteen (27%) women had at least one first-trimester miscarriage, of whom 8 (53%) had a history of infertility. Cumulative dose or timing of last RTX infusion was not associated with an increased risk of miscarriage. Only 2 (5.4%) women experienced relapses, one during pregnancy and the other postpartum. We observed no increase in adverse pregnancy outcomes compared with expected national incidence rates and remarkably little disease activity in RTX-treated women with MS, particularly when compared with periconceptional natalizumab-treated cohorts. However, larger studies are needed to fully assess the safety of RTX use before pregnancy, especially risks associated with prolonged B-cell depletion and hypogammaglobulinemia. Until these data are available, we recommend restricting RTX use before pregnancy to women who require highly effective MS treatments. This study provides Class IV evidence that for pregnant women with MS, RTX controls disease activity and does not increase adverse pregnancy outcomes.


Sowing the seeds of skepticism: Russian state news and anti-GMO sentiment.
Biotech news coverage in English-language Russian media fits the profile of the Russian information warfare strategy described in recent military reports. This raises the question of whether Russia views the dissemination of anti-GMO information as just one of many divisive issues it can exploit as part of its information war, or if GMOs serve more expansive disruptive purposes. Distinctive patterns in Russian news provide evidence of a coordinated information campaign that could turn public opinion against genetic engineering. The recent branding of Russian agriculture as the ecologically clean alternative to genetically engineered foods is suggestive of an economic motive behind the information campaign against western biotechnologies.


A unified path seeking algorithm for IMRT and IMPT beam orientation optimization.
Objective. Fully automated beam orientation optimization (BOO) for intensity-modulated radiotherapy and intensity modulated proton therapy (IMPT) is gaining interest, since achieving optimal plan quality for an unknown number of fixed beam arrangements is tedious. Fast group sparsity-based optimization methods have been proposed to find the optimal orientation, but manual tuning is required to eliminate the exact number of beams from a large candidate set. Here, we introduce a fast, automated gradient descent-based path-seeking algorithm (PathGD), which performs fluence map optimization for sequentially added beams, to visualize the dosimetric benefit of one added field at a time.Approach. Several configurations of 2-4 proton and 5-15 photon beams were selected for three head-and-neck patients using PathGD, which was compared to group sparsity-regularized BOO solved with the fast iterative shrinkage-thresholding algorithm (GS-FISTA), and manually selected IMPT beams or one coplanar photon VMAT arc (MAN). Once beams were chosen, all plans were compared on computational efficiency, dosimetry, and for proton plans, robustness.Main results. With each added proton beam, Clinical Target Volume (CTV) and organs at risk (OAR) dosimetric cost improved on average across plans by [1.1%, 13.6%], and for photons, [0.6%, 2.0%]. Comparing algorithms, beam selection for PathGD was faster than GS-FISTA on average by 35%, and PathGD matched the CTV coverage of GS-FISTA plans while reducing OAR mean and maximum dose in all structures by an average of 13.6%. PathGD was able to improve CTV [Dmax, D95%] by [2.6%, 5.2%] and reduced worst-case [max, mean] dose in OARs by [11.1%, 13.1%].Significance. The benefit of a path-seeking algorithm is the beam-by-beam analysis of dosimetric cost. PathGD was shown to be most efficient and dosimetrically desirable amongst group sparsity and manual BOO methods, and highlights the sensitivity of beam addition for IMPT in particular.


Osmotic stress in colony and planktonic cells of Pseudomonas putida mt-2 revealed significant differences in adaptive response mechanisms.
Planktonic cells and those grown on surfaces (or as colony biofilm) are known to show significant differences regarding growth behavior, cell physiology, gene expression and stress tolerance. In order to compare stress behavior of different growth forms, shake cultures for planktonic growth and agar plate cultivation for colony growth, were carried out with the well investigated model organism, Pseudomonas putida mt-2. Cells were exposed to sodium chloride to cause osmotic stress as one main environmental stressor bacteria have to cope with when growing in soil. Planktonic cells were more tolerant with a complete inhibition of growth at 0.7 M NaCl, compared to 0.5 M for agar-grown cells. Cell surface hydrophobicity, measured as water contact angles, was significantly higher for agar-grown cells (92°) than for planktonic cells (40°), and increased in the presence of NaCl. Agar-grown cells also showed a significantly higher degree of saturation of membrane fatty acids that increased in the presence of NaCl. These results demonstrate that planktonic and colony grown bacteria show different responses when confronted with osmotic stress suggesting that the tolerance and adaptive mechanisms are dependent on the environmental conditions as well as the initial physiological state.


Escherichia coli capsule bacteriophages. VII. Bacteriophage 29-host capsular polysaccharide interactions.
Different interactions between particles of Escherichia coli capsule bacteriophage 29 and its receptor, the E. coli serotype 29 capsular polysaccharide have been studied. The inactivation of phage 29 (8 x 10(3) PFU/ml) by isolated host capsular glycan was found to be physiologically insignificant (50% inactivation dose equals 100 mug after 1 h at 37 C). No adsorption (less than 2 x 10(4) PFU/mug) of the viruses to K29 polysaccharide-coated erythroyctes (at 0 or 37 C) was observed either. The phage particles were, however, found to catalyze the hydrolysis of beta-D-glucosido-(1leads to 3)-D-glucuronic acid bonds (arrow) in the receptor polymer, leading, ultimately, to the formation of a mixture of K29 hexasaccharide (one repeating unit), dodecasaccharide, and octadecasaccharide: (see article). Testing derivatives of K29 polysaccharide, as well as 82 heterologous bacterial (mainly Enteriobactericeae) capsular glycans, the viral glycanase was found to be highly specific; in accordance with the host range of phage 29, only one enzymatic cross-reaction (with the Klebsiella K31 polysaccharide) was observed. These and previous results, as well as the electron optical findings of M. E. Bayer and H. Thurow (submitted for publication), are discussed in terms of a unifying mechanism of phage 29-host capsule interaction. We propose that the viruses penetrate the capsules by means of their spike-associated glycanase activity, which leads them along capsular polysaccharide strands to membrane-cell wall adhesions where ejection of the viral genomes occurs.


Octreotide in the treatment of refractory diarrhea.
Refractory chronic diarrhea that does not respond to specific antimicrobial therapy or standard unspecific medication may present a challenging and serious clinical problem. Octreotide is a candidate drug for the treatment of these patients as it inhibits gastrointestinal motility, pancreatic secretion and inhibits intestinal absorption. Only few mostly uncontrolled studies in small patient groups were published evaluating the efficacy of octreotide in the treatment of patients with chemotherapy-induced diarrhea, short-bowel syndrome, AIDS-associated diarrhea and other conditions with chronic diarrhea not responding to standard treatment. Most of these studies are not conclusive as they yielded either negative or controversial results. Octreotide may be tried in the treatment of refractory diarrhea, in particular AIDS-associated diarrhea if patients do not respond to conventional treatment strategies. Well-designed controlled trials in large patient groups are needed in order to define the place of octreotide in the treatment of patients with refractory diarrhea.


Progress report.
Nursing Standard is following the progress of a group of students through their training. They have now reached the halfway stage.


Reducing inequities through participatory research and community empowerment.
Information dissemination for behavior change has been the mainstay of traditional health education practice, despite lack of demonstrated effectiveness in improving the public's health. Following a critique of traditional health education practice, an alternative orientation is proposed. Health education for social change, based on Paulo Freire's empowerment education and principles of participatory research, is examined theoretically within the context of the need to address inequities in health. The theoretical justification forms the basis for a description of a case study in reducing nutritional inequities. The case study analyzes how a process of participatory research and community organization was an empowering educational experience for a group of low-income urban women. The process of learning and social action is highlighted by chronicling changes associated with the experience. The realities and limitations of the project are also reflected upon. Implications for health education practice and future social change are highlighted.


The antimicrobial activity of extracts of the lichen Cladonia foliacea and its (-)-usnic acid, atranorin, and fumarprotocetraric acid constituents.
The antimicrobial activity of the chloroform, diethyl ether, acetone, petroleum ether, and ethanol extracts of the lichen Cladonia foliacea and its (-)-usnic acid, atranorin, and fumarprotocetraric acid constituents against 9 bacteria and fungi has been investigated. The extracts and pure compounds alone were found active against the same bacteria and the same yeasts. Bacillus cereus, Bacillus subtilis, Staphylococcus aureus, Streptococcus faecalis, Proteus vulgaris, Listeria monocytogenes, Aeromonas hydrophila, Candida albicans, and Candida glabrata growth were inhibited. In addition, the MICs of the extracts, (-)-usnic acid, atranorin and fumarprotocetraric acid were determined.


Numerical modelling of cancellous bone damage using an orthotropic failure criterion and tissue elastic properties as a function of the mineral content and microporosity.
Elastic and strength properties of lamellar tissue are essential to analyze the mechanical behaviour of bone at the meso- or macro-scale. Although many efforts have been made to model the architecture of cancellous bone, in general, isotropic elastic constants are assumed for tissue modelling, neglecting its non-isotropic behaviour. Therefore, isotropic damage laws are often used to estimate the bone failure. The main goals of this work are: (1) to present a new model for the estimation of the elastic properties of lamellar tissue which includes the bone mineral density (BMD) and the microporosity, (2) to address the numerical modelling of cancellous bone damage using an orthotropic failure criterion and a discrete damage mechanics analysis, including the novel approach for the tissue elastic properties aforementioned. Numerical homogenization has been used to estimate the elastic properties of lamellar bone considering BMD and microporosity. Microcomputed Tomography (μ-CT) scans have been performed to obtain the micro-finite element (μ-FE) model of cancellous bone from a vertebra of swine. In this model, lamellar tissue is orientated by considering a unidirectional layer pattern being the mineralized collagen fibrils aligned with the most representative geometrical feature of the trabeculae network. We have considered the Hashin's failure criterion and the Material Property Degradation (MPDG) method for simulating the onset and evolution of bone damage. The terms of the stiffness matrix for lamellar tissue are derived as functions of the BMD and microporosity at tissue scale. Results obtained for the apparent yield strain values agree with experimental values found in the literature. The influence of the damage parameters on the bone mechanics behaviour is also presented. Stiffness matrix of lamellar tissue depends on both BMD and microporosity. The new approach presented in this work enables to analyze the influence of the BMD and porosity on the mechanical response of bone. Lamellar tissue orientation has to be considered in the mechanical analysis of the cancellous bone. An orthotropic failure criterion can be used to analyze the bone failure onset instead of isotropic criteria. The elastic property degradation method is an efficient procedure to analyze the failure propagation in a 3D numerical model.


Genomic signal processing for DNA sequence clustering.
Genomic signal processing (GSP) methods which convert DNA data to numerical values have recently been proposed, which would offer the opportunity of employing existing digital signal processing methods for genomic data. One of the most used methods for exploring data is cluster analysis which refers to the unsupervised classification of patterns in data. In this paper, we propose a novel approach for performing cluster analysis of DNA sequences that is based on the use of GSP methods and the K-means algorithm. We also propose a visualization method that facilitates the easy inspection and analysis of the results and possible hidden behaviors. Our results support the feasibility of employing the proposed method to find and easily visualize interesting features of sets of DNA data.


Community-acquired invasive aspergillosis and outdoor filamentous fungal spore load: a relationship?
The daily number of outdoor spores was counted and the cases of community-acquired invasive aspergillosis (IA) were observed over a period of 31 months. The outdoor fungal load preceding IA occurrences was significantly higher than that measured during IA-free periods, underlining the importance of preventive measures to protect high-risk patients, even at home.


Toba-CPD: An Extended Chemical Percolation Devolatilization Model for Tobacco Pyrolysis.
Tobacco features chemical compositions different from that of raw lignocellulosic biomass. Currently, the performance of network models, like Bio-Chemical Percolation Devolatilization (Bio-CPD), on tobacco pyrolysis is unclear, and only global kinetics have been proposed for tobacco devolatilization, which does not have the versatility for a wide range of heating conditions and tobacco types. To address this issue, the present work first assessed the performance of the Bio-CPD model on tobacco pyrolysis through an a priori study, which showed large deviations. Afterward, an extended Chemical Percolation Devolatilization model for tobacco pyrolysis (Toba-CPD) was developed by modifying the kinetic parameters using a grid-search optimization strategy. The process of grid-search optimization strategy is based on the kinetic parameters of the Bio-CPD model and modified with experimental results of 11 tobacco types under a wide range of heating rates. Finally, the performance of Toba-CPD was measured with experimental results which were not used during parameters optimization. Results demonstrated that the Toba-CPD models could well reproduce the pyrolysis of various tobacco types under a wide range of heating rates (R 2 > 0.957).


Expression of vitamin D receptor and 25-hydroxyvitamin D3-1{alpha}-hydroxylase in normal and malignant human colon.
Considerable evidence exists to support the use of vitamin D to prevent and/or treat colorectal cancer. However, the routine use of bioactive vitamin D, 1,25-dihydroxyvitamin D3, is limited by the side effect of toxic hypercalcemia. Recent studies, however, suggest that colonic epithelial cells express 25-hydroxyvitamin D3-1alpha-hydroxylase, an enzyme that converts nontoxic pro-vitamin D, 25-hydroxycholecalciferol [25(OH)D3], to its bioactive form. Yet, nothing is known as to the cellular expression of 1alpha-hydroxylase and the vitamin D receptor (VDR) in the earliest histopathologic structures associated with malignant transformation such as aberrant crypt foci (ACF) and polyps [addressing the possibility of using nontoxic 25(OH)D3 for chemoprevention], nor is anything known as to the expression of these proteins in colorectal cancer as a function of tumor cell differentiation or metastasis [relevant to using 25(OH)D3 for chemotherapy]. In this study, we show that 1alpha-hydroxylase is present at equal high levels in normal colonic epithelium as in ACFs, polyps, and colorectal cancer irrespective of tumor cell differentiation. In contrast, VDR levels were low in normal colonic epithelial cells; were increased in ACFs, polyps, and well-differentiated tumor cells; and then declined as a function of tumor cell de-differentiation. Both 1alpha-hydroxylase and VDR levels were negligible in tumor cells metastasizing to regional lymph nodes. Overall, these data support using 25(OH)D3 for colorectal cancer chemoprevention but suggest that pro-vitamin D is less likely to be useful for colorectal cancer chemotherapy.


Oxysterol binding protein-related protein-5 is related to invasion and poor prognosis in pancreatic cancer.
In previous studies, the gene expression profiles of two hamster pancreatic cancer cells with different potentials for invasion and metastasis were analyzed. In the present study, we identified that one of the genes expressed strongly in the highly metastatic cell line is hamster oxysterol binding protein-related protein (ORP)-5. The aim of the present study was to clarify the relationship between ORP5 and invasion and poor prognosis of human pancreatic cancer. Invasion assays were carried out in both hamster and human pancreatic cancer cells by suppressing the ORP5 gene with short interfering RNA or inducing its expression by introducing an expression vector. To evaluate the relationship between ORP5 and the characteristics of human pancreatic cancer, 56 pancreatic cancer tissue specimens were analyzed and the ORP5 expression in each pancreatic cancer tissue specimen was analyzed by immunohistochemistry. In both the hamster and human pancreatic cancer cells, suppression of ORP5 significantly reduced the invasion rate of the cells and induction of ORP5 significantly enhanced the invasion rate of the cells. In the clinical sample, the median survival times of the patients with ORP5-positive (n = 33) and ORP5-negative (n = 23) cancer were 8.3 and 17.2 months, respectively (P = 0.02). Also, the 1-year survival rates of patients with ORP5-positive and ORP5-negative cancer were 36.4 and 73.9%, respectively (P = 0.005). The ORP5 expression level was related to both invasion and poor prognosis in human pancreatic cancer. These findings suggest that the expression of ORP5 may induce cancer cell invasion, resulting in the poor prognosis of pancreatic cancer.


The Study of Nrf2 Signaling Pathway in Ovarian Cancer.
Ovarian cancer is one of the most malignant gynecological tumors in the world, with a high fatality rate and resistance to chemotherapy. Much basic research has revealed that oxidative stress is involved in tumor occurrence and development processes and is associated with tumor progression as well as metastasis. In recent years, oxidative stress has been proven to have a close connection with malignant biological behavior in ovarian cancer, and this topic has garnered increasing attention. This article reviews the research aimed toward elucidating the relationship between oxidative stress and ovarian cancer.


Ethical Dimensions of Public Health Actions and Policies With Special Focus on COVID-19.
During pandemics, the ethicists, public health professionals, and human rights advocates raise a red flag about different public health actions that should, at best, be addressed through integrated, global policies. How to rationalize the healthcare resources and prioritize the cases is not a recent challenge but the serious concern about that is how to achieve this while not increasing the vulnerability of the disadvantaged population. Healthcare professionals use different scoring systems as a part of their decision-making so the medical teams and triage committees can allocate resources for predictable health outcomes and prognosis as well as to appropriately triage the patients accordingly. However, the value of the existing scoring systems to manage COVID-19 cases is not well-established yet. Part of this problem includes managing non-COVID patients with chronic medical conditions like non-communicable diseases and addressing their medical needs during the pandemic complex context in a way to avoid worsening their conditions and, on the other hand, avoid hindering the establishment of comprehensive standards for dealing with COVID-19. In this article, we discuss this dilemma as well as how preexisting ethical standards were challenged by COVID-19. We also discuss how monitoring the consistent application of ethical standards during the medical trials of new medications, vaccines, or unproven medical interventions is also a critical issue.


Lysophosphatidic acid level and the incidence of silent brain infarction in patients with nonvalvular atrial fibrillation.
Lysophosphatidic acid (LPA), which is proposed to play an important role in normal physiological situations such as wound healing, vascular tone, vascular integrity and reproduction, may be involved in the etiology of some diseases such as atherosclerosis, cancer, obesity or myocardial infarction. Abnormal findings, including silent brain infarction (SBI), are frequently observed by magnetic resonance imaging (MRI) in patients with nonvalvular atrial fibrillation (NVAF). However, whether there is a relationship between LPA level and the prevalence of SBI has not been extensively studied. In the present study, the association between them was investigated. 235 patients with NVAF, 116 cases of SBI without NVAF and 120 cases of healthy volunteers (control group), who did not receive any antithrombotic therapy, were enrolled in this study. Plasma LPA levels in the NVAF with SBI group were significantly higher than that in the control group (p < 0.01), NVAF without SBI group (p < 0.01) and SBI without NVAF group (p < 0.01). The LPA levels are lower in the control group than in the NVAF without SBI and SBI without NVAF groups (p < 0.01), however, the latter two groups did not significantly differ from each other for LPA levels (p > 0.05) There were significant differences in the positive rate of platelet activation between each of the groups (p < 0.01). The positive rate of platelet activation was significantly higher in the NVAF with SBI group. We suggest that LPA might be a novel marker for estimation of the status of platelet activation and the risk factor for SBI onset in NVAF patients. We expected that plasma LPA levels could predict the occurrence of SBI in NVAF patients.


Factors associated with death in women with intimate partner violence notification in Brazil.
Intimate partner violence (IPV) is a social and public health concern. This article aims to identify factors associated with death in women with IPV notification. This is a case-control study based on the record-linkage of the Mortality Information System (SIM), from 2011 to September/2017, and the Notifiable Diseases Information System (SINAN), 2011 to 2016. The "case" group consisted of women aged 15 to 59 years old with notification of violence on SINAN, whose author was current or former intimate partner and died by any cause registered on SIM. The "control" group consisted of women 15-59 years old, living in the same municipality of the cases and victim of IPV registered on SINAN, but without a death record on SIM. Multiple logistic regression was used to estimate the odds ratio of death. 151,826 Brazilian women were victim of IPV and were notified by SINAN, and 2,538 died. The main cause of death was homicide. The following characteristics conferred a greater chance of death: having race/skin-color black or yellow; having disabilities; living in rural area; physical violence, torture and multiple types combined; violence perpetrated by a firearm, a sharp object and multiple means combined.


[Association Between Parenting Styles and Symptoms of Attention Deficit Hyperactivity Disorder].
We aimed to study characteristics of child and mother reported parenting styles of children with Attention Deficit Hyperacitivity Disorder (ADHD) and association of parenting styles of mothers with demographic and clinical variables like ADHD symptoms, sex, age, ADHD subtype, and comorbidity. 58 children with ADHD and 30 healthy children were included in this study. All children were assessed by The Schedule for Affective Disorders and Schizophrenia for School Aged Children- Present and Lifetime Version. ADHD symptom severity was assessed by The Conners Parent Rating Scale and The Conners Teacher Rating Scale. The Parenting Style Inventory (PSI) and The Parental Attitude Research Instrument (PARI) were used to assess parenting styles of mothers. ADHD group had lower scores on two subscales of PSI (acceptance/involvement and strictness/supervision) and democratic attitude and equality subscale of PARI and higher scores on strict discipline subscale of PARI compared to control group. In ADHD group, higher symptoms of oppositional defiant disorder were associated with higher mother's strict discipline scores and lower child reported mother's acceptance/involvement scores. Our findings supported the idea that there may be an association between parenting attitudes and ADHD symptoms in families having a child with ADHD. These results indicated the importance of integrated approach to ADHD diagnosis and treatment and evaluating the child with ADHD in the context of family environment.


Pharmacokinetics of gemcitabine in Japanese cancer patients: the impact of a cytidine deaminase polymorphism.
Gemcitabine is rapidly metabolized to its inactive metabolite, 2',2'-difluorodeoxyuridine (dFdU), by cytidine deaminase (CDA). We previously reported that a patient with homozygous 208A alleles of CDA showed severe adverse reactions with an increase in gemcitabine plasma level. This study extended the investigation of the effects of CDA genetic polymorphisms on gemcitabine pharmacokinetics and toxicities. Genotyping of CDA was performed by a direct sequencing of DNA obtained from the peripheral blood of Japanese gemcitabine-naïve cancer patients (n = 256). The patients recruited to the association study received a 30-minute intravenous infusion of gemcitabine at a dose of either 800 or 1,000 mg/m2, and eight blood samples were periodically collected (n = 250). Plasma levels of gemcitabine and dFdU were measured by high-performance liquid chromatography. Plasma CDA activities toward cytidine and gemcitabine were also measured (n = 121). Twenty-six genetic variations, including 14 novel ones and two known nonsynonymous single nucleotide polymorphisms (SNPs), were detected. Haplotypes harboring the nonsynonymous SNPs 79A>C (Lys27Gln) and 208G>A (Ala70Thr) were designated *2 and *3, respectively. The allelic frequencies of the two SNPs were 0.207 and 0.037, respectively. Pharmacokinetic parameters of gemcitabine and plasma CDA activities significantly depended on the number of haplotype *3. Haplotype *3 was also associated with increased incidences of grade 3 or higher neutropenia in the patients who were coadministered fluorouracil, cisplatin, or carboplatin. Haplotype *2 showed no significant effect on gemcitabine pharmacokinetics. Haplotype *3 harboring a nonsynonymous SNP, 208G>A (Ala70Thr), decreased clearance of gemcitabine, and increased incidences of neutropenia when patients were coadministered platinum-containing drugs or fluorouracil.


Eptifibatide bridging therapy for staged carotid artery stenting and cardiac surgery: Safety and feasibility.
Prophylactic carotid artery stenting (CAS) is an effective strategy to reduce perioperative stroke in patients with severe carotid stenosis who require cardiothoracic surgery (CTS). Staging both procedures (CAS-CTS) during a single hospitalization presents conflicting demands for antiplatelet therapy and the optimal pharmacologic strategy between procedures is not established. The purpose of this study is to present our initial experience with a "bridging" protocol for staged CAS-CTS. A retrospective review of staged CAS-CTS procedures at a single referral center was performed. All patients had multivessel coronary and/or valvular disease and severe carotid stenosis (>70%). Patients not previously on aspirin were also started on aspirin prior to surgery, followed by eptifibatide during CAS (intraprocedural bolus followed by post-procedural infusion which was continued until the morning of surgery). Pre- and perioperative (30 days) neurologic morbidity and mortality was the primary endpoint. 11 CAS procedures were performed in 10 patients using the protocol. The median duration of eptifibatide bridge therapy was 36 h (range 24-288 h). There was one minor bleeding complication (1/11, 9.1%) and no major bleeding complications during the bridging and post-operative period. There was one post-operative, non-neurologic death and zero perioperative ischemic strokes. For patients undergoing staged CAS-CTS, Eptifibatide bridging therapy is a viable temporary antiplatelet strategy with a favorable safety profile. This strategy enables a flexible range of time-intervals between procedures.


Current thoughts on the role of the androgen receptor and prostate cancer progression.
Androgens play a central role in the development and maintenance of prostate tissue. Treatment of prostate cancer by androgen ablation either surgically or biochemically results in massive cell death and tumor regression. However, this is often followed by the onset of aggressive disease, which is fatal. Various studies have been conducted to understand the mechanism leading to the establishment of aggressive disease following treatment. An interesting comprehensive study recently conducted by Chen et al shows the increase in androgen receptor (AR) transcript to be the key factor in disease recurrence following treatment. This up-regulation in the AR levels is shown to increase sensitivity to low levels of androgen, leading to ligand-dependent downstream gene expression and tumor recurrence. A "mass action" model has been proposed to explain this phenomenon. Moreover, the increase in mRNA levels has been shown to facilitate conversion of classic antagonists to agonists of hormones action by the recruitment of a subset of co-activators to the promoters of AR-responsive genes. This study underscores the importance of ARs in the establishment of prostate cancer and offers several insights into the mechanism by which tumors recur following androgen ablation. The study also prompts several questions about the reason behind the observed up-regulation and also the mechanism by which classic antagonists are rendered agonistic. The need for the design of novel therapeutic analogues is also emphasized.


Effect of rifampin and bacitracin on nasal carriers of Staphylococcus aureus.
Anterior nares cultures from 664 hospital personnel identified 165 (24.8%) as carriers of Staphylococcus aureus. Persistent carriers (17.8%) were identified and randomly assigned to one of four treatment groups: rifampin (600 mg once a day for 5 days), bacitracin ointment (topically applied three times a day for 10 days), combined rifampin and bacitracin, and control (no treatment). Bacitracin ointment was ineffective in eliminating S. aureus from the anterior nares and had a postreatment carrier rate equal to the control rate. Rifampin therapy caused a highly significant reduction (79%) in carriage; however, combined therapy was not as effective as treatment with rifampin alone. Of 132 strains of staphylococci isolated before and after treatment, all were susceptible to less than 0.016 micrograms of rifampin per ml. This study demonstrates that rifampin may be an effective antistaphylococcal antibiotic and could be used to control the carrier state in high-risk situations.


1H-MRS of the anterior cingulate cortex in childhood and adolescent obsessive-compulsive disorder: a case-control study.
Abnormal glutamate concentrations in the anterior cingulate cortex (ACC) have been identified in children and adults with obsessive-compulsive disorder (OCD). The purpose of the present study was to measure in vivo (1)H-MRS neurometabolite concentrations in the ACC of children and adolescents with OCD, in order to identify metabolite abnormalities compared to healthy controls and to assess their relationship with clinical variables. 3T proton-magnetic resonance spectroscopy was used to probe ACC biochemistry in 47 paediatric and adolescent OCD patients (11-18 years old) compared to 31 healthy subjects of similar age, sex and estimated intellectual quotient. There were no significant differences in the concentration of glutamate plus glutamine (Glx) adjusted for CSF between OCD patients and healthy controls [F1,74=0.00; P=0.943], but there were significant differences in the concentration of Glx adjusted for CSF in paediatric and adolescent OCD patients according to duration of illness (less than or more than 24 months) [F2,73=3.95; P=0.024]. In addition, we found significantly lower levels of myo-inositol adjusted for CSF in the ACC [F1,74=5.686; P=0.02] in patients compared with controls. The present findings do not confirm the hypothesis of differences in Glx concentrations in the ACC between children and adolescents with OCD and healthy controls; however, the observation of differences in the Glx concentration in children and adolescent OCD patients depending on the duration of illness is of interest.


Administration of dexamethasone prior to training blocks ACTH-induced recovery of an extinguished avoidance response.
Pretest administration of ACTH has been shown to produce recovery of an extinguished avoidance response. Presumably this effect is found because endogenous ACTH is a component of the original training memory. However, another possible explanation of this finding is that administration of the peptide acts as a novel stimulus that "disinhibits" the extinguished response. In order to test this "disinhibitory" hypothesis of ACTH-induced recovery of an extinguished avoidance response, some subjects were given dexamethasone 2 hr prior to training and extinction. This synthetic glucocorticoid is effective in blocking endogenous release of ACTH. Thus, ACTH should not be a component of the training memory in subjects given dexamethasone prior to training and extinction but would be a relatively novel stimulus condition at testing. Pretest administration of ACTH was found to be effective in alleviating performance deficits induced by extinction only for subjects given saline prior to training and extinction. Administration of ACTH had no effect on the avoidance responding of subjects given dexamethasone. These findings suggest that pretest administration of ACTH affects retrieval processes rather than acts as a disinhibitor.


Electroreductive dimerization of coumarin and coumarin analogues at carbon cathodes.
Electrochemical reduction of coumarin (1), 6-methylcoumarin (2), 7-methylcoumarin (3), 7-methoxycoumarin (4), and 5,7-dimethoxycoumarin (5) at carbon cathodes in dimethylformamide containing 0.10 M tetra-n-butylammonium tetrafluoroborate has been investigated by means of cyclic voltammetry and controlled-potential (bulk) electrolysis. Cyclic voltammograms for reduction of 1-5 exhibit two irreversible cathodic peaks: (a) the first peak arises from one-electron reduction of the coumarin to form a radical-anion intermediate, which is protonated by the medium to give a neutral radical; (b) although most of this radical undergoes self-coupling to yield a hydrodimer, reduction of the remaining radical (ultimately to produce a dihydrocoumarin) causes the second cathodic peak. At a potential corresponding to the first voltammetric peak, bulk electrolysis of 1-5 affords the corresponding hydrodimer as a mixture of meso and dl diastereomers. Although the meso form dominates, the dl-to-meso ratio varies, due to steric effects arising from substituents on the aromatic ring. Electroreduction of an equimolar mixture of 1 and 4 gives, along with the anticipated symmetrical hydrodimers, an unsymmetrical product derived from the two coumarins. A mechanistic scheme involving both radical-anion and radical intermediates is proposed to account for the formation of the various products.


Results of peri-articular steroid injection in the treatment of chronic extra-articular pain after total knee arthroplasty.
The authors conducted study to analyze results of peri-articular steroid injection in the treatment of chronic pain from soft tissue inflammation after total knee arthroplasty (TKA). The authors retrieved data from all patients underwent TKA whom suffered with chronic extra-articular pain and received local peri-articular steroid injection by 2 senior authors during January 1, 2008 to June 30, 2010. Clinical evaluation such as pain score, knee score and functional score were recorded pre-injection and three months after injection. 554 TKA cases were operated during January 1, 2008 and June 30, 2010. 29 knees from 28 female patients were injected with steroid injection and included in the present study. Mean age of 64.7 year and mean BMI of 27.7. Three patients in this group were diagnoses as Diabetes. The most common site of injection was in Tibia, with either Anserinus bursa or around Gerdy's tubercle. Mean time to injection after operation was 5 months. Mean VAS was reduced from 56.5 +/- 20.32 to 20.57 +/- 16.1. Mean knee score and functional score were improved from 74.62 +/- 14.24 to 85.71 +/- 11.85 and from 53.4 +/- 22.57 to 67.04 +/- 21.17 consecutively. All clinical difference has statistically significant with p-value < 0.05. There was no incident of superficial or deep infection at mean follow-up time of 2 years and 5 months. Local steroid injection is a safe and effective choice for treatment of pain from chronic soft tissue inflammation after TKA.


Bivalves from the latest Jurassic-earliest Cretaceous hydrocarbon seep carbonates from central Spitsbergen, Svalbard.
The bivalve fauna from the latest Jurassic-earliest Cretaceous hydrocarbon seep deposits from central Spitsbergen, Svalbard comprises at least 17 species, four of which belong to chemosymbiotic taxa often found at seeps. These are the solemyid Solemya (Petrasma) cf. woodwardiana; Nucinella svalbardensis sp. nov., which belongs to a group of large Nucinella species known from seeps and deep water environments; the lucinid bivalve, Tehamatea rasmusseni sp. nov., included in a genus widely distributed in other Jurassic-Cretaceous seeps; and Cretaxinus hurumi gen. et sp. nov., which is the oldest known thyasirid and is discussed in relation to other large seep-restricted genera in this family. The remaining species in the fauna belong to 'background' genera known from coeval normal marine sediments, mostly from the Boreal area. These include the nuculid Dacromya chetaensis, two new malletiids (Mesosaccella rogovi sp. nov. and M. toddi sp. nov.), the oxytomiid Oxytoma octavia, at least three Buchia species, at least two pectinids, including Camptonectes (Costicamptonectes) aff. milnelandensis and Camptonectes (Camptochlamys) clatrathus, the limid Pseudolimea arctica, the arcticid Pseudotrapezium aff. groenlandicum, and the pholadomyid Goniomya literata. The large number of 'background' species in the bivalve fauna is probably a reflection of the shallow-water setting of the Svalbard seeps. This might also explain the lack of the seep-restricted modiomorphid bivalve Caspiconcha from the fauna. With solemyids, Nucinella, lucinids and thyasirids, the latest Jurassic-earliest Cretaceous bivalve seep fauna of Svalbard contains typical representatives of the Mesozoic bivalve seep faunas, both long established and young evolutionary colonists.


Exposure to mobile phone radiation opens new horizons in Alzheimer's disease treatment.
Alzheimer's disease, the most common type of dementia and a progressive neurodegenerative disease, occurs when the nerve cells in the brain die. Although there are medications that can help delay the development of Alzheimer's disease, there is currently no cure for this disease. Exposure to ionizing and non-ionizing radiation may cause adverse health effects such as cancer. Looking at the other side of the coin, there are reports indicating stimulatory or beneficial effects after exposure to cell phone radiofrequency radiation. Mortazavi et al. have previously reported some beneficial cognitive effects such as decreased reaction time after human short-term exposure to cell phone radiation or occupational exposure to radar microwave radiation. On the other hand, some recent reports have indicated that RF radiation may have a role in protecting against cognitive impairment in Alzheimer's disease. Although the majority of these data come from animal studies that cannot be easily extrapolated to humans, it can be concluded that this memory enhancing approach may open new horizons in treatment of cognitive impairment in Alzheimer disease.


The effectiveness of in vivo root planing in removing bacterial endotoxin from the roots of periodontally involved teeth.
In this study, scaling alone resulted in endotoxin values considerably greater than the values for healthy root surfaces. However, the root-planed Samples contained only about 1 ng more of endotoxin than did the healthy root surfaces. This small difference can be accounted for by the presence of small flecks of calculus left after root planing. Considering that out of a total sample size of 48 surfaces there was only 1 ng difference in the amount of endotoxin between planed teeth and uninvolved teeth, the basic conclusion must be that root planing, as performed in this study, was able to render diseased root surfaces approximately as free of detectable endotoxin as were uninvolved, healthy root surfaces of unerupted teeth.


Safety assessment of traditional Plaisentif cheese.
Traditional foods are gaining more and more market due to consumers' increasing willingness to buy products linked to national cultures: among these products, cheese plays an important role. Plaisentif is a traditional Piedmont cheese, only made during violets blooming season. The aim of this work is to evaluate the safety of this cheese, taking into account the EU Regulations. Microbiological hazards as well chemical, biogenic amines and mycotoxins, analysis were investigated. Salmonella spp. and Listeria monocytogenes were never detected in cheeses after ripening. Biogenic amines were present in very low quantities. Ochratoxin A was never detected and patulin was detected in over one cheese during the two years of sampling. This is the first attempt to characterize traditional Plaisentif cheese from a safety point of view. All the information acquired can be held as a necessary basis for reinforcing the culture of traditional products, for economic opportunities in mountainous regions and for safeguarding traditions and cultural identities.


Primary testicular lymphoma: a strictly homogeneous hematological disease?
Primary testicular lymphomas display mostly aggressive diffuse large cell B-cell lymphomas, which could be further subclassified into germinal center B-cell-like and an activated B-cell phenotype via immunohistochemistry. A retrospective analysis of primary testicular lymphomas diagnosed at the Institute of Pathology, Salzburger Landeskliniken (SALK) between January 1997 and December 2008 was done. Immunohistochemical staining and complete clinical data evaluation was carried out and linked to overall survival time. We found 18 cases of primary testicular lymphoma diagnosed in elderly patients showing no side predilection and having an aggressive clinical behavior with short overall survival independent of treatment. The lymphomas could for the most be classified into diffuse large cell B-cell lymphomas [15/18 (83.3%)] showing a non-significant prevalence of activated B cell phenotype [9/15 (60%)] compared to the germinal centre phenotype [6/15 (40%)]. Two of the cases were mantle cell lymphomas consisting of the infrequent pleomorphic subtype. The survival analysis revealed no significant difference for any of the investigated antigens. Primary testicular lymphomas are for the most DLBCL, but subtype classification reveal molecular heterogeneity inside this lymphoma entity. A distinction between those subtypes is necessary because of different clinical behavior and treatment.


In whose best interests? A case study of a family affected by dementia.
Many people with dementia are cared for by family members. Family carers often feel bound to support the person with dementia at the expense of their own needs, which can be neglected. They often experience distress when making decisions, especially over ethical dilemmas when their own interests and those of the person being cared for conflict. This paper presents a case study approach to consider best interests decision making for families affected by dementia. In the case study, a carer is supporting his father to remain living at home although he feels this unsafe and the demands of this cause tension with his family and affect his performance at work.


[Effect of cardiac glycosides on the calcium ion binding by biomembrane lipids].
By using methods of fluorescent and spine (electron paramagnetic resonance) probes it was shown that cardiac glycosides (digoxin, digitoxin, convallatoxin, corelborine and strophanthin) effectively interact with biomembrane lipids enhancing conformational motility of lipids and cause additional binding of calcium ions with the membrane.


Acute pneumonitis after subcutaneous injections of silicone for augmentation mammaplasty.
In a period of 3 years, seven cases of acute pneumonitis have been found after patients have been subcutaneously injected with silicone for the sole purpose of augmentation mammaplasty. Adverse symptoms following these silicone injections were fever, hypoxemia, hemoptysis, and abnormal diffuse bilateral alveolar infiltrates in both lungs. Pulmonary hemorrhaging occurred, and this was substantiated by using the bronchoscope with the bronchoalveolar lavage (BAL). The alveolar macrophage obtained from the BAL contained large quantities of pleomorphic cytoplasmic particles, which in actual fact were silicone particles. They were identified as silicone by scanning electron microscopy and energy-dispersive analysis of x-rays. This evidently showed that silicone diffusion into the circulatory system and subsequent embolization of the lung. Pulmonary function studies had shown restrictive changes with increase or normal single-breath carbon monoxide diffusing capacity (Dsb). Perfusion lung scans were interpreted as showing diffuse abnormalities consisting of decreased peripheral uptake. Acute hypoxemic respiratory failure was noted in four of these patients. Silicone injections of this nature were therefore a respiratory risk and caused the inducement of pneumonitis.


Hepatitis C viral protein translation: mechanisms and implications in developing antivirals.
Hepatitis C viral protein translation occurs in a cap-independent manner through the use of an internal ribosomal entry site (IRES) present within the viral 5'-untranslated region. The IRES is composed of highly conserved structural domains that directly recruit the 40S ribosomal subunit to the viral genomic RNA. This frees the virus from relying on a large number of translation initiation factors that are required for cap-dependent translation, conferring a selective advantage to the virus especially in times when the availability of such factors is low. Although the mechanism of translation initiation on the Hepatitis C virus (HCV) IRES is well established, modulation of the HCV IRES activity by both cellular and viral factors is not well understood. As the IRES is essential in the HCV life cycle and as such remains well conserved in an otherwise highly heterogenic virus, the process of HCV protein translation represents an attractive target in the development of novel antivirals. This review will focus on the mechanisms of HCV protein translation and how this process is postulated to be modulated by cis-acting viral factors, as well as trans-acting viral and cellular factors. Numerous therapeutic approaches investigated in targeting HCV protein translation for the development of novel antivirals will also be discussed.


Fatal Work-Related Injuries: Southeastern United States, 2008-2011.
In 2008, the work-related injury fatality rate was 3.8 per 100,000 workers in the United States but was 5.2 per 100,000 workers for the southeast region. Work-related fatalities in the southeast were examined for the period 2008 to 2011. Median work-related injury fatality rates are reported for the southeast region, each of the 12 states, and the United States. The percentages of employees in high fatality industries and work-related fatalities by cause were calculated. Finally, the Occupational Safety and Health Administration's database was searched for fatality reports. States with the highest rates (per 100,000 workers) included Arkansas (7.2), Louisiana (6.8), and West Virginia (6.6). Arkansas, Louisiana, Mississippi, and West Virginia each had more than 20% of their employees in high fatality industries. Forty percent of work-related injury fatalities were from transportation incidents in the southeast and the United States. Future analyses should include work-related injury fatality rates by industry and compare rates with other U.S. regions.


[On the problem of HIV infection in the objects of forensic medical expertise].
The authors overview the current state of research in the field of diagnostics and identification of the signs suggesting the presence of HIV in the materials obtained from the human corpses undergoing forensic medical expertise at different stages of their post-mortem changes. Another objective of the present work was to evaluate the risk of HIV infection for the medical personnel involved in the autopsy studies taking into consideration the significance attached in different countries to the problem of anti-infectious protection of the staff of the state institutions of forensic medical expertise. The authors discuss the possibilities and limitations of the application of the methods for HIV diagnostics, such as immunoenzymatic assays. The special attention is given to the advantages of the molecular genetic methods based on the use of the specific fragments of the viral RNA genome as the diagnostic markers. The solid methodological basis for molecular genetic diagnostics of HIV infection is provided by PCR-amplification with the detection in the real-time regime. It is supposed that this approach will make it possible not only to determine, with the high degree of accuracy and specificity, the presence of the viral genome in the biological materials but also to reduce to a minimum the probability of both false-positive and false-negative responses.


[A form of bladder allergy: eosynophilic cystitis].
Eosynophile cystitis is the serious result of an antigen-antibody reaction in the bladder. The rarity with which it occurs, its ambiguous clinical picture and its solely anatomo-pathological diagnosis combine to make it atypical and hence the scanty numbers of papers published on the subject. The author presents a case of his own, following a bibliographic review in which special emphasis is placed on the etiopathogeny of the process.


[The diagnostic and prognostication of glaucoma.]
The glaucoma is a leading cause of irreversible blindness in all countries. In the nearest years an increasing of patients with the given pathology is prognosticated. Nowadays, development of disease is related to alteration of interleukin profile in lacrimal fluid. however, diagnostic significance of interleukins is studied insufficiently. The purpose of study. To determine diagnostic significance of interleukins on a local level for amelioration of diagnostic and prognostication of development of glaucoma. The content of interleukins in lacrimal fluid was analyzed in 80 patients with glaucoma stage II and 45 healthy individuals using technique of sandwich-linked enzyme-linked immunosorbent assay with calculation of informativeness of indices of immunity. The results. The analysis established high diagnostic significance of IL-2, IL-17, IL-8 for verification of glaucoma. They are proposed to be applied in laboratory diagnostic and prognostication of disease. The developed regression model ensures with high accuracy prognostication of development of glaucoma in case of increased level of IL-2, IL-17, IL-8.


Submental lipectomy with skin excision.
A new method of excision of submental skin and fat with modified Z-incision affords easy excision, wide exposure, and simple closure. Thirty-two patients over an 18-year period have had satisfactory results with inconspicuous scars. Modification of platysma muscles and subplatysmal fat excision are facilitated by the wide exposure. Use of this method has been limited to those cases in which a large submental fold is present in a patient who declines to have a regular rhytidectomy or in cases of residual submental redundancy after a complete rhytidectomy. Occasionally, a rhytidectomy is not sufficient.


The effects of hyperthyroidism on MIBG uptakes in the human heart--preliminary report.
Twelve cases of hyperthyroidism with cardiac manifestations (4 males, 8 females, ages: 20 to 70 years) and 12 normal controls of euthyroidism (6 males, 6 females, ages: 27 to 70 years) were included in our study. Each case accepted an I.V. injection of I-131 MIBG (I.R.E., Belgium) with 0.5mCi/1.7m2 of body surface area. The 24 and 48 hr imagings of the anterior chest, including total heart and lungs, were used to estimate cardiac sympathetic nerve innervation by the following formula: H/L = (the mean counts of pixels in the regions of interest (ROI) over the heart)/(the mean counts of pixels in the ROI over the lungs). The results showed that the 24 and 48 hr H/L values in euthyroidism were a little higher than those in hyperthyroidism, but the differences were not significant by a Wilcoxon rank sum test. The correlation between H/L and 24 hr I-131 thyroid uptake in patients with hyperthyroidism were also evaluated and the results showed no significant correlation between the H/L and uptake. In conclusion, we consider that the clinical manifestations concerning the heart in hyperthyroidism may not totally depend on the effects of increased cardiac sympathetic nerve innervation.