Effect of aging on kinetic parameters of 3 alpha(beta)-hydroxysteroid oxidoreductases in epithelium and stroma of human normal and hyperplastic prostate.
The accumulation of 5 alpha-dihydrotestosterone (DHT), particularly in stroma, is a possible etiological factor in regard of the age-dependent development of benign prostatic hyperplasia (BPH). In this context, we have recently demonstrated age-dependent alterations of 5 alpha-reductase, which is responsible for the irreversible conversion of testosterone to DHT. Therefore, it was also of interest to study possible age-dependent alterations of those enzymes mainly involved in the reversible metabolism of DHT to 5 alpha-androstanediols. Thus, we determined, in the presence of NADPH/NADP+, kinetic parameters [Km and maximum velocity (Vmax)] of 3-hydroxysteroid oxidoreductases (3 alpha-HSORred, 3 beta-HSORred, and 3 alpha-HSORox) in separated epithelium and stroma of 10 normal (NPR) and 20 hyperplastic prostates (BPH) and correlated the data with the age of the donors (15-86 yr). The mean Km (nanomolar concentrations +/- SEM) of 3 alpha-HSORred was significantly (P less than 0.01) higher in epithelium (NPR, 1391 +/- 181; BPH, 2150 +/- 157) than in stroma (NPR, 778 +/- 22; BPH, 749 +/- 62), indicating the presence of epithelial and stromal enzymes. The mean Km values of 3 beta-HSORred and 3 alpha-HSORox were similar. Concerning 3 alpha-HSORred, the mean potential capacity, i.e. the quotient of Vmax/Km (+/- SEM), was significantly (P less than 0.01) higher in epithelium (0.56 +/- 0.08) than in stroma (0.19 +/- 0.02) of NPR, while in BPH nearly identical mean potential capacities were found in epithelium (0.33 +/- 0.04) and stroma (0.26 +/- 0.02). The respective Vmax/Km of 3 beta-HSORred and 3 alpha-HSORox were significantly (P less than 0.05) lower. In addition, the potential capacity of all three enzymes was distinctly lower than the potential DHT-forming capacity of 5 alpha-reductase. With advancing age, the Vmax/Km decreased significantly (P less than 0.001; 3 alpha-HSORred and 3 beta-HSORred) or tendentiously (3 alpha-HSORox) in epithelium, while in stroma a significant (P less than 0.001; 3 alpha-HSORred and 3 alpha-HSORox) or tendentious (3 beta-HSORred) increase with age was found. Our results indicate that aging has a significant impact on DHT-removing enzymes. However, these enzymes counterbalance only in part the strong potential capacity of 5 alpha-reductase.


Improvement of Memory by Means of Ultra-Low Doses of Antibodies to S-100B Antigen.
Antigen S-100B of nervous tissue, according to the data of numerous studies, affects the mechanisms of nervous system plasticity and memory. The influence of ultralow doses of antibodies to S-100B (6C dilution, according to the homeopathic pharmacopoeia) has been studied on three learning behavioral models on Wistar rats, which were inhibitory avoidance, choosing of bowls with sucrose and feeding behavior cessation after auditory signal. For all three tasks, parameters of reproduction of the learned skills improved after per oral administration of potentiated antibodies to S-100B antigen immediately after learning. Possible mechanisms of the anti-S-100B antibodies influence on memory formation are discussed.


Systemic Lupus Erythematosus Presenting with Alveolar Hemorrhage.
Diffuse alveolar hemorrhage is a rare presentation of systemic lupus erythematosus. Early diagnosis and appropriate treatment can improve outcome. An 18-year-old male presented with hemoptysis and respiratory distress requiring orotracheal intubation. Laboratory tests showed positive anti-nuclear antibody and anti-dsDNA and low C3 and C4. Bronchoalveolar lavage became progressively hemorrhagic after each aliquot. He was treated with pulse methylprednisolone, cyclophosphamide, and plasma exchanges. Alveolar hemorrhage is a rare initial presentation of lupus, with mortality rates reported at about 50%. Lupus should be considered in those presenting with alveolar hemorrhage since delay in therapy may cause a rapid deterioration of the patient. The diagnosis of SLE is illusive when DAH is the presenting symptom. Since early diagnosis and appropriate institution of treatment improve outcome, it is important to keep lupus in mind as an etiology of alveolar hemorrhage. Pulse methylprednisolone, cyclophosphamide, and plasmapheresis therapy resulted in rapid improvement of respiratory function in our patient.


Analysis of alpha-synuclein, dopamine and parkin pathways in neuropathologically confirmed parkinsonian nigra.
The identification of mutations that cause familial Parkinson's disease (PD) provides a framework for studies into pathways that may be perturbed also in the far more common, non-familial form of the disorder. Following this hypothesis, we have examined the gene regulatory network that links alpha-synuclein and parkin pathways with dopamine metabolism in neuropathologically verified cases of sporadic PD. By means of an in silico approach using a database of eukaryotic molecular interactions and a whole genome transcriptome dataset validated by qRT-PCR and histological methods, we found parkin and functionally associated genes to be up-regulated in the lateral substantia nigra (SN). In contrast, alpha-synuclein and ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) gene expression levels were significantly reduced in both the lateral and medial SN in PD. Gene expression for Septin 4, a member of the GTP-binding protein family involved in alpha-synuclein metabolism was elevated in the lateral parkinsonian SN. Additionally, catalase and mitogen-activated protein kinase 8 and poly(ADP-ribose) polymerase family member 1 (PARP1) known to function in DNA repair and cell death induction, all members of the dopamine synthesis pathway, were up-regulated in the lateral SN. In contrast, two additional PD-linked genes, glucocerebrosidase and nuclear receptor subfamily 4, group A, member 2 (NR4A2) showed reduced expression. We show that in sporadic PD, parkin, alpha-synuclein and dopamine pathways are co-deregulated. Alpha-synuclein is a member of all three gene regulatory networks. Our analysis results support the view that alpha-synuclein has a central role in the familial as well as the non-familial form of the disease and provide steps towards a pathway definition of PD.


Perceived subjective versus objective knowledge: Consumer valuation of genetically modified certification on food producing plants.
Previous research has identified subjective and objective knowledge as determinants of consumers' acceptance of genetically modified organisms (GMO) in the medical and food industries. In contrast to a large body of literature on the effects of attitudes or knowledge on food preferences, the extent to which consumers' knowledge affects their valuation of non-GMO food producing plants (i.e., plants grown for food or ornamental purposes) is less understood. This manuscript investigates the relationship between consumers' knowledge of relevant non-GMO certification programs and their acceptance and willingness-to-pay (WTP) for non-GMO plants. The first study used an Internet respondent panel and choice experiment, while the second study utilized an in-person experimental auction. In line with previously reported low public acceptance of genetically modified food products, respondents were receptive of and willing to pay premiums for non-GMO food producing plants. This study found that subjective and objective knowledge impacted the premiums for non-GMO labels, with the high subjective and low objective knowledge group generating the highest WTP. Low subjective and low objective knowledge resulted in the lowest WTP. Findings suggest a disconnect between subjective and objective knowledge of non-GMO certification programs, which in turn influences consumer valuation of those products.


Induction of amylase and protease as antibiofilm agents by starch, casein, and yeast extract in Arthrobacter sp. CW01.
In unfavourable environment, such as nutrient limitation, some bacteria encased themselves into a three dimensional polymer matrix called biofilm. The majority of microbial infections in human are biofilm related, including chronic lung, wound, and ear infections. The matrix of biofilm which consists of extracellular polymeric substances (EPS) causes bacterial colonization on medical implanted device in patients, such as catheter and lead to patient's death. Biofilm infections are harder to treat due to increasing antibiotic resistance compared to planktonic microbial cells and escalating the antibiotic concentration may result into in vivo toxicity for the patients. Special compounds which are non-microbicidal that could inhibit or destroy biofilm formation are called antibiofilm compounds, for example enzymes, anti-quorum sensing, and anti-adhesins. Arthrobacter sp. CW01 produced antibiofilm compound known as amylase. This time our preliminary study proved that the antibiofilm compound was not only amylase, but also protease. Therefore, this research aimed to optimize the production of antibiofilm agents using amylase and protease inducing media. The five types of production media used in this research were brain heart infusion (BHI) (Oxoid), BHI with starch (BHIS), casein with starch (CS), yeast extract with starch (YS), and casein-yeast extract with starch (CYS). Biofilm eradication and inhibition activities were assayed against Pseudomonas aeruginosa (ATCC 27,853) and Staphylococcus aureus (ATCC 25,923). The results showed that different production media influenced the antibiofilm activity. Addition of starch, casein and yeast extract increased the production of amylase and protease significantly. Higher amylase activity would gradually increase the antibiofilm activity until it reached the certain optimum point. It was shown that crude extracts which contained amylase only (BHI, BHIS and YS) had the optimum eradication activity against P. aeruginosa and S. aureus biofilm around 60-70 %. Meanwhile, CS and CYS crude extracts which contained both amylase and protease increased the biofilm eradication activity against both pathogens, which were around 70-90 %. It was concluded that the combination of amylase and protease was more effective as antibiofilm agents against P. aeruginosa and S. aureus rather than amylase only.


Histochemical heterogeneity of dispersed human lung mast cells.
Cytocentrifuge preparations of enzymatically dispersed human lung parenchymal mast cells were examined by light microscopy after fixation in either Mota's basic lead acetate or 10% neutral buffered formalin followed by toluidine blue staining at pH 0.5. Fixation in Mota's basic lead acetate allowed detection of all mast cells. However, after formalin fixation only 10.8 +/- 1.3%, range 4.7 to 17%, n = 8 remained detectable (i.e., formalin "resistant"). Therefore, the vast majority of human lung mast cells lose their metachromatic staining after formalin fixation (i.e., are formalin "sensitive"). Mast cells were then separated on the basis of diameter by countercurrent elutriation and on the basis of density by discontinuous Percoll gradients. Histochemically distinct populations of mast cell types emerged in all lungs studied. The proportion of formalin-resistant mast cells increased as a function of diameter: less than 5% at diameters of less than or equal to 11 mu and densities less than or equal to 1.063 g/ml, to 30 to 40% in cells of diameters greater than or equal to 16 mu and densities greater than or equal to 1.100 g/ml. Maximum anti-IgE challenge of nearly homogeneous formalin-sensitive mast cells (94.3 +/- 2.1% purity, n = 6) caused the generation of both leukotriene C4 (64.6 +/- 26.4 pg/mast cell) and PGD2 (114.8 +/- 37.5 pg/mast cell). Six- to eight-fold enrichment of formalin-resistant mast cells did not significantly alter the histamine release response or profiles of arachidonate metabolites. Similar results were obtained for the nonimmunologic stimulus ionophore A23187. We conclude that two histochemically distinct subpopulations, of mast cells are present in human lung suspensions. Although formalin-sensitive cells account for almost 90% of lung mast cells, formalin-resistant cells are separable by their large diameters and higher densities. Both subtypes show similar histamine release responses and arachidonate oxidation profiles.


Origin of Spectral Features and Acid-Base Properties of 3,7-Dihydroxyflavone and Its Monofunctional Derivatives in the Ground and Excited States.
Comprehensive spectral investigations of 3,7-dihydroxyflavone and its two derivatives, which each contain a methyl-blocked hydroxyl group, reveal complex radiation absorption in the 300-450 nm range and emission in the 370-650 nm range. The absorption and fluorescence characteristics of these compounds depend on the pH/H0 of the water/methanol media, which is caused by the existence of the compounds in various protolytic (cationic, neutral, anionic) and tautomeric forms. Combined analysis of steady-state, time-dependent and fluorescence decay spectral data enabled the identification of the emitting species, determination of their lifetimes with respect to radiative and nonradiative deactivation processes, fluorescence quantum yields, protolytic and tautomeric abilities under various conditions, and acidic dissociation constants of the cationic, neutral, and anionic forms of the compounds. Results of calculations carried out at the DFT and TD DFT levels of theory generally confirmed the experimental findings concerning tautomeric/protolytic transformations and equilibria. Computational methods also provided insight into possible tautomerization pathways. Electronically excited molecules are generally much more susceptible to tautomerization and acidic dissociation than ground-state ones. 3,7-Dihydroxyflavone exhibits distinguishable features among the compounds investigated and can be considered as potential spectral indicator of properties (polarity, hydrophobicity, hydrogen-bonding ability) and acidity/basicity of liquid environments.


Topologically-Interlocked Minicircles as Probes of DNA Topology and DNA-Protein Interactions.
Invited for the cover of this issue are Prof. Takashi Morii and co-workers at Kyoto University and Ewha Womans University. The cover image depicts the graphical design and atomic force microscopic (AFM) images of the synthesized topologically-interlocked DNA catenane and rotaxanes inside a frame-shaped DNA origami. Read the full text of the article at 10.1002/chem.202200108.


The role of autonomic nervous system in the pathophysiology of hemifacial spasm.
Despite the vascular compression of the seventh cranial nerve has been verified by the microvascular decompression surgery as the cause of hemifacial spasm (HFS), the mechanism of the disease is still unknown. We believe that the autonomic nervous system in adventitia of the offending artery may contribute to the HFS. To prove our hypothesis, we performed an experiment in SD rats. Moller's HFS model was adopted and the abnormal muscle response (AMR) wave was electrophysiologically monitored. With randomization, some HFS rats underwent exclusion of the offending artery or removal of the ipsilateral superior cervical ganglion. Some HFS rats with negative AMR following exclusion of the offending artery were dripped with norepinephrine onto the neurovascular conflict site. With exclusion of the offending artery, AMR disappeared in 14 (70%) of the 20 HFS rats, while in three (30%) of the 10 from sham operation group (P<0·05). With ganglionectomy, AMR disappeared in 12 (75%) of the 16 HFS rats, while in two (25%) of the eight from the sham operation group (P<0·05). With norepinephrine drip, AMR reappeared in four (67%) of the six from those offending-artery-excluded HFS rats, while in zero of the six from normal-saline-dripped group (P<0·05). The neurotransmitter releasing from the autonomic nervous endings in the worn adventitia of the offending artery may induce an ectopia action potential in those demyelinated facial nerve fibers expanding to the neuromuscular conjunction and trigger an attack of HFS.


Molecular Determinants of Chronic Liver Disease as Studied by NMR-Metabolomics.
Chronic liver diseases are one of the major causess of mortality worldwide. It can manifest through many different forms including chronic virus infection, alcohol abuse, metabolic syndromes such as non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. At early stages, the liver can repair the damage produced by the insult. However, upon continuous damage, the accumulation of molecules triggers fibrosis, which subsequently progresses towards cirrhosis and, ultimately, hepatocarcinoma. Early diagnosis of liver disease and a proper staging of fibrosis are crucial in therapy since drugs are only effective at incipient and intermediate stages of the disease. In this context, liver biopsy is the gold standard, but it is invasive and can produce complications. Metabolomics has emerged as a potent discipline to identify new biomarkers in a non-invasive way. Here, we compile and critically review the existing NMR-based metabolomics studies on chronic liver diseases, specifically covering non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, alcoholic liver disease and those produced by virus infection.


Species diversity of black flies (Diptera: Simuliidae) in Oriental region and molecular phylogeny of the subgenus Gomphostilbia members.
Black flies (Diptera: Simuliidae) are ecologically and medically important insects. Female adults of black flies are the solitary vectors of river blindness (onchocerciasis) and their larvae play a vital role in stream ecosystem. This study examined the distribution of black flies in the Oriental region and analyzed the phylogenetic relationship of the subgenus Gomphostilbia members based on two molecular loci. The distribution data of black fly species in different countries of Oriental region were obtained from world black flies geographic inventory. The two gene sequences, COI and ITS1 were used to study the phylogenetic relationships of the members of subgenus Gomphostilbia members. The distribution analysis revealed that out of the 16 subgenera in the genus Simulium Latreille s., the species-level diversity of three subgenera (Gomphostilbia, Nevermannia and Simulium) contributes about thrice of total black fly species diversity. The highest diversity of species was found in the subgenus Simulium. The strict consensus of Tree analysis using New Technology (TNT) and Maximum Likelihood (ML) recovered similar topolo- gies for Gomphostilbia members and they formed as monophyly. The overall sequence identities of the 19 species of subgenus Gomphostilbia were high and shared 55-60% similarity. Results of this study highlighted that eight subgenera of Simulium Latreille s. str are commonly distributed in different parts of Oriental region. Among these the subgenera of Simulium, Gomphostilbia and Nevermannia are most common with high diversity in China, Pakistan, Thailand and Vietnam. The phylogenetic analysis of Gomphostilbia members demonstrates the inter-specific divergence, indicating the centre of origin (India) or the recipient of ancestral migrant lineages in Oriental region.


Adults with cyanotic congenital heart disease: hematologic management.
Hematologic management of adults with cyanotic congenital heart disease has received little recent attention. The lack of practical therapeutic guidelines prompted us to consolidate our observations on 124 cyanotic adults for general physicians, cardiologists, and hematologists who care for these patients. Specific attention focused on regulation of erythrocyte mass and concepts of compensated and decompensated erythrocytosis, symptoms of deficient tissue oxygen transport, hyperviscosity and iron deficiency, the potential relation between elevated hematocrit levels and brain injury, hemostasis, urate metabolism, and renal function. Cerebral infarction was not seen in any patient. Phlebotomy is best reserved for treatment of symptomatic hyperviscosity. Iron therapy is indicated for symptomatic iron deficient erythropoiesis. Abnormal hemostatic mechanisms are the rule. Antithrombotic medications have little or no role in treatment. Hyperuricemia is the result of abnormal renal uric acid excretion not urate overproduction, and serves as a marker of abnormal renal function. Drugs that promote urate excretion are the preferred maintenance treatment in symptomatic hyperuricemic patients.


Lithiation-Enabled High-Density Nitrogen Vacancies Electrocatalyze CO2 to C2 Products.
Electrochemical CO2 reduction to produce valuable C2 products is attractive but still suffers with relatively poor selectivity and stability at high current densities, mainly due to the low efficiency in the coupling of two *CO intermediates. Herein, it is demonstrated that high-density nitrogen vacancies formed on cubic copper nitrite (Cu3 Nx ) feature as efficient electrocatalytic centers for CO-CO coupling to form the key OCCO* intermediate toward C2 products. Cu3 Nx with different nitrogen densities are fabricated by an electrochemical lithium tuning strategy, and density functional theory calculations indicate that the adsorption energies of CO* and the energy barriers of forming key C2 intermediates are strongly correlated with nitrogen vacancy density. The Cu3 Nx catalyst with abundant nitrogen vacancies presents one of the highest Faradaic efficiencies toward C2 products of 81.7 ± 2.3% at -1.15 V versus reversible hydrogen electrode (without ohmic correction), corresponding to the partial current density for C2 production as -307 ± 9 mA cm-2 . An outstanding electrochemical stability is also demonstrated at high current densities, substantially exceeding CuOx catalysts with oxygen vacancies. The work suggests an attractive approach to create stable anion vacancies as catalytic centers toward multicarbon products in electrochemical CO2 reduction.


Primary and Revision Lumbar Discectomy: A Four-Year Review from Our Private Practice.
The surgical treatment of symptomatic lumbar disc herniation is now focused on nerve root decompression with preservation of the bony and ligamentous stabilizers of the spine. Various techniques of discectomy have been devised in accordance with this principle and irrespective of the technique used; primary disc surgeries have generally known to give good results. This retrospective study was done in different private clinics & hospitals of Dhaka city, Bangladesh from January 2012 to December 2015. Of the 105 lumbar discectomies performed during the study period, 95(90.4%) patients fulfilled the inclusion criteria and were included in the analysis. Of these, 90 patients had primary discectomy, while the remaining 5 were revision surgeries. The follow-up varied from 1-4 years, but the clinical outcomes were evaluated at the end of one year from surgery in all the patients. In the primary surgery group there were 50(55.56%) men and 40(44.44%) women, while the revision group had 01(20%) men and 04(80%) women. The age distribution was similar in both the groups, with the maximum numbers (44% and 42.9%) in the fourth decade of life. Of the 05 patients who underwent revision surgery, 03 belonged to the primary surgery group of this study, while the remaining 02 had undergone their primary surgery elsewhere. Excluding the two residual discs, the remaining 03 patients with recurrences gave a history of complete resolution of symptoms after the primary surgery. Amongst these, 3(60%) had a history of a precipitating event prior to onset of pain, 2 had a definitive history of significant lack of physical activity. The time interval between the primary and revision surgery ranged from three months to 10 years (average 2.6 years).


Autoimmunity, end organ damage, and the origin of autoantibodies and autoreactive T cells in systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is a prototype of systemic autoimmunity affecting many systems. Both antibodies and autoreactive T cells play significant roles in its pathogenesis. Experimental data and clinical observations indicate that autoimmunity and end organ damage are under separate genetic controls and that there are significant interactions between these two pathways. Experimental evidence has been obtained to support the hypothesis that autoantibodies and autoreactive T effector cells may be initiated by environmental factors through molecular mimicry and the inherent polyreactive nature of antigen receptors. A unified hypothesis has been postulated for the pathogenesis of SLE that has practical implications.


How to manage water hygiene successfully.
According to Alan Hambidge, who has over 22 years' experience in health and safety risk management, and is an expert in legionellosis and water hygiene, 'recent developments and research' have resulted in 'an increase in the Health and Safety Executive's expectations' on the standards adopted by healthcare organisations in looking after their water systems. In our latest technical guidance article, he explores 'some of the developments, pitfalls, and traps, that indicate the requirement for improvement in competence'.


[Isolation and characteristics of monoclonal antibodies to influenza virus types A and B].
Monoclonal antibodies (MCA) to influenza type A (10F) and B (5H and 6H) viruses have been prepared. By immunoblotting method, MCA 10F were found to be specific for NP-protein of influenza A virus, and MCA 5H and 6H to be specific for hemagglutinin of influenza B virus. It was established that the 10F clone interacted with all the investigated influenza A virus strains with different antigenic formulae (H1N1, H2N2, H3N2) and could be used for typing of this virus type. Clones 5H and 6H react specifically with hemagglutinins of influenza B viruses isolated in 1940, 1979, and 1983 which makes them useful for diagnosis of influenza B.


Naturally Occurring Steroidal Saponins as Potential Anticancer Agents: Current Developments and Mechanisms of Action.
Cancer is claimed as a prevalent cause of mortality throughout the world. Conventional chemotherapy plays a pivotal role in the treatment of cancers, but multidrug resistance has already become one of the major impediments to efficacious cancer therapy, creating a great demand for the development of novel anticancer drugs. Steroidal saponins, abundantly found in nature, possess extensive structural variability, and some naturally occurring steroidal saponins exhibit profound anticancer properties through a variety of pathways. Hence, naturally occurring steroidal saponins are powerful lead compounds/candidates in the development of novel therapeutic agents. This review article described the recent progress of naturally occurring steroidal saponins as potential anticancer agents, and the mechanisms of action were also discussed, covering articles published between 2017 and 2021.


Accuracy of Estimated Fetal Weight by Ultrasound Versus Leopold Maneuver.
Estimated fetal weight (EFW) is frequently used for clinical decision-making in obstetrics. The goals of this study were to determine the accuracy of EFW assessments by Leopold and ultrasound and to investigate any associations with maternal characteristics. Postgraduate years 1 and 2 obstetrics and gynecology resident physicians from Harbor-UCLA Medical Center from 2014 to 2020 performed EFW assessments on 10 preterm (<37 weeks' gestational age) fetuses by ultrasound biometry and 10 full-term (≥37 weeks' gestational age) fetuses by ultrasound biometry and Leopold maneuver. Assessments were included if the patients delivered within 2 weeks of the assessments. One thousand six hundred ninety-seven EFW assessments on 1183 patients performed by 33 residents were analyzed; 72.6% of sonographic full-term EFWs, 69% of Leopold full-term EFWs, and 61.5% of sonographic preterm EFWs were within 10% of the neonatal birth weight (BW). The lowest estimation error in our study occurred when actual BW was 3600 to 3700 g. After adjusting for BW, residents were found to have lower accuracy when the mother had a higher body mass index (BMI) for full-term estimation methods (Leopold and ultrasound, β = 0.13 and 0.12, P = 0.001 and 0.002, respectively). Maternal BMI was not related to estimation error for preterm fetuses (β = 0.01, P = 0.75). Clinical and sonographic EFW assessments performed by obstetrics and gynecology junior residents are within 10% of neonatal BW much of the time. In our cohort, they tended to overestimate EFWs of lower-BW infants and underestimate EFWs of higher-BW infants. Accuracy of full-term EFW assessments seems to decrease with increasing maternal BMI.


Differential patterns of cyclosporine A-induced inhibition of humoral and cellular immune responses to sheep erythrocytes in mice.
In this communication we reveal differential inhibitory effects of cyclosporine A (CsA) on generation of the cellular and humoral immune responses to sheep erythrocytes (SRBC) in mice. For the analysis of the regulatory effects of CsA, we analyzed the results of 45 separate experiments performed in recent years where CsA served as a reference drug for our research on various immunoregulatory compounds. The humoral immune response was determined as the number of plaque-forming cells (PFC), and the delayed type hypersensitivity (DTH) was measured by foot pad swelling. We demonstrated that treatment of mice intraperitoneally (ip) with a dose of 100 microg of CsA/mouse, 2 h after immunization resulted in a differential pattern of inhibition of these two types of the immune response depending on the magnitude of the response in a given experiment. In the case of the antibody response (mean number of PFC 2312 median 2200), high PFC numbers were inhibited stronger than low ones; mean values in respective quarters and inhibitory actions were the following: 1,552 (42.3%), 2,049 (52.4%), 2,441 (61.2%) and 3042 (62.5%). In consequence, high, medium and low responses were down-regulated to approximately the same level. Another inhibitory pattern was observed in the DTH model (mean 10.35 units, median 10.8 units), i.e. low DTH responses were suppressed more strongly than high ones. The mean DTH responses and suppression effects in respective quarters were: 7.4 (58.2%), 10.1 (52.7%),11.8 (51.8%) and 13.1 (38.8%). As the result of such CsA action, the DTH response profile was parallel to that of the control response. In summary, the humoral immune response was down-regulated by CsA proportionally to the immune response observed in control mice, while DTH response was inversely proportional. The possible mechanisms of the observed regulatory CsA actions are discussed.


[The 150 years anniversary of Italy: a memorandum from the South].
The 150 years anniversary of Italy: a memorandum from the South. The tables and figures presented show the differences between North and South of Italy in term of position in the rank of wellbeing indexes, unemployment, poverty (number of poor individuals and families) and per capita consumptions. Health care workers should be aware of these differences in the interpretation of health care data and in the planning of health interventions.


Positron emission tomography with O-(2-[18F]fluoroethyl)-l-tyrosine versus magnetic resonance imaging in the diagnosis of recurrent gliomas.
New treatment modalities are available for patients with glioma, which may lead to unspecific changes in posttherapeutic magnetic resonance imaging (MRI) findings. Differentiation between tumor- and therapy-associated contrast enhancement on MRI scans after treatment may be difficult. The aim of this study was to analyze the diagnostic value of O-(2-[F]fluoroethyl)-l-tyrosine (FET)-positron emission tomography (PET) and MRI in the detection of tumor recurrence in patients with glioma after radiotherapy, radiosurgery, or multimodal treatment. The study included 36 patients with gliomas and neuroradiological diagnosis of tumor recurrence and 9 patients who had undergone radioimmunotherapy. Patients were consecutively treated between September 2001 and May 2003. A contemporary FET-PET investigation was performed in all patients. A tissue diagnosis was made for comparative analysis in all patients with progressive neuroradiological or clinical findings (32 of 45 patients). In patients with transient neuroradiological or clinical deterioration (13 of 45 patients), clinical follow-up was used to support or contradict the imaging-based diagnosis. Tumor recurrence was documented in 31 of 45 patients, and 14 of 45 patients were tumor free. FET-PET and MRI revealed a correct diagnosis in 44 and 36 patients, respectively. The difference was statistically significant (P < 0.01). Concordant findings after MRI and FET-PET were documented in 37 patients and discordant findings in 8 patients. The difference was statistically significant (P < 0.01). Specificity of FET-PET was 92.9%, and sensitivity was 100% (in patients suspected of having recurrent tumor as revealed by MRI). Sensitivity of MRI was 93.5%, and specificity was 50% (P < 0.05). For patients with gliomas undergoing multimodal treatment or various forms of irradiation, conventional follow-up with MRI is insufficient to distinguish between benign side effects of therapy and tumor recurrence. FET-PET is a powerful tool to improve the differential diagnosis in these patients.


Bone marrow colony-stimulating activity of sera in infectious mononucleosis.
From 44 to 100% of sera from patients with infectious mononucleosis exhibited the capacity to stimulate colony formation in vitro by mouse bone marrow cells. The proportion of sera with colony-stimulating activity was highest in patients with a short fever period and developing low Paul-Bunnell titres. Patients with a more severe course of the disease generally displayed no, or only weak, colony-stimulating activity in their sera, and also had higher Paul-Bunnell titres. The level of serum colony-stimulating activity tended to fall in the convalescent stages of the disease.


Spirituality for nurses and their practice.
This descriptive study compared the inclusion of spirituality in the practice of two groups of nurses: nurses prepared in parish nursing (PN) and nurses not specifically prepared in spiritual care (NonPN). The Spirituality in Nursing Care tool was used to determine sources of spiritual strength and spiritual experiences of the respondents, the application of spirituality in their practice, and the interventions and indicators they used in determining the need for spiritual assistance. Random sampling using U.S. postal codes selected 600 members from a national mailing list of nurses prepared in parish nursing and 600 similarly selected nurses not prepared in parish nursing. A total of 645 questionnaires were returned with complete data. The following question was asked: How do nurses prepared in providing spiritual care (PN) compare to nurses not similarly prepared (NonPN) in terms of: (a) personal sources of spiritual strength, (b) spiritual experiences, (c) application of spirituality in their practice, (d) identification of indicators of spiritual needs in their clients, and (e) interventions used to meet the spiritual needs of their clients? The findings indicate there are differences in how PN and NonPN groups of nurses respond to spirituality of self and their use of spirituality in clinical practice. It is suggested that parish nurses take the lead to further study spirituality and the indicators and appropriate interventions, and identify patient outcomes when spiritual needs are addressed by nurses in providing "holistic nursing practice."


Encephalitogenicity for rats of myelin basic protein without the aid of water-in-oil emulsions.
The induction of experimental allergic encephalomyelitis (EAE) with purified myelin basic protein (MBP) has, heretofore, required its incorporation in a water-in-oil emulsion or adsorption on particulate adjuvants. In the present work, the absorption of a saline solution of MBP from the peritoneal cavity into the mediastinal lymph nodes was increased by giving repeated inoculations or by pretreating rats with a peritoneal irritant. Under these conditions, the only adjuvant needed for production of EAE was aqueous pertussis vaccine which was injected separately a few hours or one day after the MBP. Pertussis vaccine was also necessary for production of EAE with intradermal injection of aqueous MBP. By injecting the aqueous MBP directly into pre-enlarged popliteal lymph nodes, it was possible to produce EAE without the pertussis vaccine. Thus, EAE can be induced in rats using MBP without the addition of Freund's adjuvant or pertussis vaccine.


Fidaxomicin: a new macrocyclic, RNA polymerase-inhibiting antibiotic for the treatment of Clostridium difficile infections.
Clostridium difficile infection is now a major concern throughout the developed world and its occurrence is a consequence of broad-spectrum antibiotic therapy primarily in the elderly in-patient population and high spore loads in hospitals in these regions. With the emergence of a hypervirulent, endemic strain, more severe disease is being recognized and is occurring in previously considered unusual patient groups. Vancomycin and metronidazole are the current mainstays for therapy of severe and nonsevere disease, respectively. Relapse is a major concern, with treatment options for these cases often difficult. Any new drug must be better than vancomycin for severe disease with fewer relapses. Fidaxomicin, a macrocyclic RNA polymerase inhibitor, has a narrow spectrum of activity, which is almost C. difficile specific. This drug appears to have a higher clinical cure rate than vancomycin, and fewer patients relapse following initial treatment. From the results of a recent Phase III trial, fidaxomicin appears to be an extremely promising drug for treating C. difficile infection and preventing relapses.


Pathological and immunophenotypic features of adult non-Hodgkin's lymphomas by age group.
To elucidate age-related differences in non-Hodgkin's lymphoma (NHL), the authors evaluated 950 consecutive, human immunodeficiency virus-negative patients (age range, 15 to 96 years) observed between July 1988 and June 1995 in the same Italian cancer institute. Patients were grouped into six age groups and cross-tabulated by Working Formulation (WF) categories and other newly recognized entities according to the Revised European American Lymphoma (REAL) classification, cell immunophenotype, and nodal or extranodal location. There was a tendency of the low-grade category to increase with increasing age (16.8% in the age group 15 to 34 years to 32.4% in the age group 65 to 74 years), although a subsequent decline was seen at age 75 years or older (23.2%). Also the intermediate-grade category was more frequent in the elderly (46.6% and 49.4% at 65 to 74 years and at 75 years or older, respectively). High-grade category showed compared with low and intermediate grade ones, a significant downward trend with age (X2 for trend = 25.31; P < .001), interrupted in only the oldest age group. The relative excess of low-grade NHL in patients older than 55 years. of age was accounted for by the high proportion of small lymphocytic lymphomas, which, however, somewhat declined at age 75 years or older. Conversely, the relative excess of high-grade NHL below age 35 years chiefly derived from the high percentage (28.4%) of CD30-positive anaplastic large cell lymphomas. B- and T-cell lymphomas accounted for 85.9% and 9.0% of all cases, respectively. B- and T- and non-B, non-T-cell and histiocytic NHL accounted for the remaining 5.1%. A highly significant trend of increase in the proportion of B-cell lymphomas with age increase was noted (X2 for trend = 21.90; P < .001); chiefly attributable to the excess of T-cell (15.1%) and undetermined phenotype (18.6%) in patients younger than 35 years of age. Extranodal location was not significantly related to age groups. Thus, the present study showed some interesting differences in NHL morphology and cell phenotype according to age, avoiding, at the same time, the arbitrariness of patients' dichotomization into elderly and nonelderly.


A long term study of root retention in the treatment of maxillary molars with furcation involvement.
A study was done to evaluate long-term results of treating 387 maxillary molars with furcation involvement in 100 patients with chronic destructive periodontal disease. Results showed a favorable long term functional survival rate of 341 teeth (88%) 5 to 24 years after treatment, despite the fact that many teeth had at least one root with 50% or less of bone support before treatment. Of the 46 teeth (12%) that were ultimately extracted, 25 were present for a significant length of time (6 to 18 years) before extraction. The radiographs of 292 teeth (75%) showed no significant change in bone support 5 to 24 years after treatement, while those of 8 teeth (2%) suggested improvement. There was perceptible increase in bone loss in 41 teeth (11%). Forty-six (12 %) were extracted. All periodontally involved teeth in each patient of the study were treated. Specific treatment for maxillary molars with furaction involvement included soft tissue therapy; coronal reshaping, if indicated; and instruction in home care. Considerable emphasis was placed on improving occlusal function. In no case was root amputation, hemisection, osseous surgery, or reshaping of the cervical area of the tooth done. A total of 366 (94%) of the teeth did not have endodontic therapy before, during, or after the study. Therefore endodontic therapy was not a significant factor in retention of the 341 teeth.


Vibrational frequency and dipolar orientation of the protonated Schiff base in bacteriorhodopsin before and after photoisomerization.
Light-driven proton transport in bacteriorhodopsin (BR) is initiated by photoisomerization of the retinylidene chromophore, which perturbs the hydrogen bonding network in the Schiff base region of the active site. This study aimed to identify the frequency and dipolar orientation of the N-D stretching vibrations of the Schiff base before and after photoisomerization, by means of low-temperature polarized FTIR spectroscopy of [zeta-(15)N]lysine-labeled BR in D(2)O. (15)N-shifted modes were found at 2123 and 2173 cm(-1) for BR, and at 2468 and 2495 cm(-1) for the K intermediate. The corresponding N-H stretches are at approximately 2800 cm(-1) for BR and 3350-3310 cm(-1) for the K intermediate. The shift to a 350 cm(-1) higher frequency upon photoisomerization is consistent with loss of the hydrogen bond of the Schiff base. The N-D stretch frequencies of the Schiff base in BR and the K intermediate are close to the O-D stretch frequencies of strongly hydrogen bonded water and Thr89, respectively. The angles of the dipole moments of the N-D stretches to the membrane normal were determined to be 60-65 degrees for BR and approximately 90 degrees for the K intermediate. In the case of BR, the stretch orientation is expected to deviate from the N-D bond orientation due to vibrational mixing in the hydrogen bonding network. In contrast, the data for the K intermediate suggest that the N-D group is not hydrogen bonded and orients along the membrane.


Circulating regulatory T cell subsets predict overall survival of patients with unresectable pancreatic cancer.
Most patients with pancreatic ductal adenocarcinoma (PDAC) have unresectable cancers with a dismal prognosis, in which cohort chemotherapy is the primary treatment. T cell immune adaption is critical for tumor immune escape and prognosis of this disease. The present study aimed to determine the correlation between peripheral T cell subset distribution in patients with unresectable PDAC and their response to chemotherapy. Two hundred and twelve patients with unresectable PDAC were included whose blood samples were collected for analysis of T cell subsets, including CD3+, CD4+, CD8+, CD8+CD28+ and CD4+CD25+CD127 T cells by flow cytometry before and after gemcitabine-based chemotherapy. Enzyme-linked immunosorbent assay was used to detect the expression levels of tumor growth factor (TGF)-β1, interleukin (IL)-6 and IL-17A in the patients before and after chemotherapy. Univariate and multivariate analyses found that an initial CD4/CD8 ratio or T regulatory (Treg) cell level before any treatment was associated with the prognosis of unresectable PDAC. After two cycles of chemotherapy, there was no significant change in percentages of T cell subsets, except elevation to a higher level of CD3+ T cells. Decreased Tregs or CD4/CD8 ratio after two cycles of chemotherapy predicts a longer overall survival (OS). Levels of Tregs in stable disease (SD) and partial remission (PR) cases significantly decreased after chemotherapy, but increased in progressive disease (PD) patients. There was no correlation between Tregs and the expression level of either TGF-β1 or IL-6. IL-17A expression was elevated in Treg-decreased patients, whereas IL-17A was reduced in Treg-increased patients after chemotherapy. The circulating signature of T cell subsets can predict OS and chemotherapeutic response in patients with unresectable PDAC, and may be attributable to the plasticity of T cell subsets.


Pathways of Intergenerational Transmission of Advantages during Adolescence: Social Background, Cognitive Ability, and Educational Attainment.
Educational attainment in adolescence is of paramount importance for attaining higher education and for shaping subsequent life chances. Sociological accounts focus on the role of differences in socioeconomic resources in intergenerational reproduction of educational inequalities. These often disregard the intergenerational transmission of cognitive ability and the importance of children's cognitive ability to educational attainment. Psychological perspectives stress the importance of cognitive ability for educational attainment but underemphasize potentially different roles of specific socioeconomic resources in shaping educational outcomes, as well as individual differences in cognitive ability. By integrating two strands of research, a clearer picture of the pathways linking the family of origin, cognitive ability, and early educational outcomes can be reached. Using the population-based TwinLife study in Germany, we investigated multidimensional pathways linking parental socioeconomic position to their children's cognitive ability and academic track attendance in the secondary school. The sample included twins (N = 4008), respectively ages 11 and 17, and siblings (N = 801). We observed strong genetic influences on cognitive ability, whereas shared environmental influences were much more important for academic tracking. In multilevel analyses, separate dimensions of socioeconomic resources influenced child cognitive ability, controlling parental cognitive ability. Controlling adolescent cognitive ability and parental cognitive ability, parental socioeconomic resources also directly affected track attendance. This indicated that it is crucial to investigate the intertwined influences on educational outcomes in adolescence of both cognitive ability and the characteristics of the family of origin.


Applications for multifrequency ultrasound biomicroscopy in mice from implantation to adulthood.
A new multifrequency (19-55 MHz) ultrasound biomicroscope with two-dimensional imaging and integrated Doppler ultrasound was evaluated using phantoms and isoflurane-anesthetized mice. Phantoms revealed the biomicroscope's lateral resolution was between 50 and 100 microm, whereas that of a conventional 13 MHz ultrasound system was 200-500 microm. This difference was apparent in the markedly higher resolution images achieved using the biomicroscope in vivo. Transcutaneous images of embryos in pregnant mice from approximately 2 days after implantation (7 days gestation) to near term (17.5 days) were obtained using frequencies from 25 to 40 MHz. The ectoplacental cone and early embryonic cavities were visible as were the placenta and embryonic organs throughout development to term. We also evaluated the ability of the biomicroscope to detect important features of heart development by examining embryos from 8.5 to 17.5 day gestation in exteriorized uteri using 55 MHz ultrasound. Cardiac looping, division of the outflow tract, and ventricular septation were visible. In postnatal imaging, we observed the heart and kidney of neonatal mice at 55 MHz, the carotid artery in juveniles (approximately 8 g body wt) and adults (approximately 25 g body wt) at 40 MHz, and the adult heart, aorta, and kidney at 19 MHz. The coefficient of variation of carotid and aortic diameter measurements was 1-3%. In addition, blisters in GRIP1 -/- embryos and aortic valvular stenosis in two adults were readily visualized. Using image-guided Doppler function, low blood velocities in vessels as small as 100 microm in diameter including the primitive heart tube at day 8.5 were measurable, but high blood velocities (>37.5 cm/s) such as in the heart and large arteries in late gestation and postnatal life were off-scale. Accurate cardiac dimension measurements were impeded by poor temporal resolution (4 frames/s). In summary, the multifrequency ultrasound biomicroscope is a versatile tool well suited to detailed study of the morphology of various organ systems throughout development in mice and for hemodynamic measurements in the low velocity range.


The fate of compound with AgF2:AgO stoichiometry-A theoretical study.
Metal oxyfluorides constitute a broad group of chemical compounds with a rich spectrum of crystal structures and properties. Surprisingly though, none of the ternary oxyfluorides contains a cation from group 11 of the periodic table. Intending to find one, we focused on the silver derivative, the Ag2OF2 system, which may be considered as the 1:1 "adduct" of AgF2 (i.e., an antiferromagnetic positive U charge transfer insulator) and AgO (i.e., a diamagnetic disproportionated negative charge transfer insulator). Here, possible crystal structures of the silver oxyfluoride were studied using evolutionary algorithms based on the density functional theory approach. We analyzed the oxidation states of silver in the low-energy structures, possible magnetic interactions, and energetic stability with respect to the available substrates. Our findings suggest that silver oxyfluoride, if obtained, may form a metastable crystal with cations in three different oxidation states of the same element. Due to the small energy difference, existence of a fully disproportionated metallic compound cannot be ruled out. Finally, we outlined a prospect for the synthesis of polytypes of interest using diverse synthetic approaches, starting from the direct fluorination of Ag2O.


Epithelial-myoepithelial carcinoma of the parotid gland.
The EME carcinoma of intercalated duct origin is now recognized as a distinct salivary gland malignancy. A case has been reported that typifies clinical and pathologic features. Both the surgeon and pathologist should learn not only to recognize its dual cellular characteristics, but also to be aware of the potential destructive nature and possibility for metastases with this tumor.


Antinociceptive and anti-inflammatory potential of Rhododendron arboreum bark.
Rhododendron arboreum Smith. (Ericaceae), an evergreen small tree, is one of the 1000 species that belongs to genus Rhododendron distributed worldwide. In folk medicine, as various parts of this plant exhibit medicinal properties, it is used in the treatment of different ailments.The present study was designed to evaluate the potential anti-inflammatory and antinociceptive effects of methanolic extract of R. arboreum bark, followed by activity-guided fractionation of n-hexane, n-butanol, chloroform, ethyl acetate and aqueous fractions.The ethyl acetate fraction (200 mg/kg i.p.) showed the maximum analgesic effect (82%) in acetic acid-induced writhing, followed, to a less extent, by crude extract and chloroform fraction both at a dose of 200 mg/kg i.p. (65.09% and 67.89%, respectively). In carrageenan-induced mouse paw oedema, the crude extract and its related fractions displayed in a dose-dependent manner (50-200 mg/kg i.p.) an anti-inflammatory activity for all time-courses (1-5 hrs). For the active extract/fractions (200 mg/kg i.p.), the maximum effect was observed 5 h after carrageenan injection. These evidences were also supported by in vitro lipoxygenase inhibitory properties. In conclusion, R. arboreum crude methanolic extract and its fractions exhibited anti-inflammatory and antinociceptive effects. For these reasons, this plant could be a promising source of new compounds for the management of pain and inflammatory diseases.


Cytoskeletal changes induced in HEp-2 cells by the cytotoxic necrotizing factor of Escherichia coli.
The effect of the cytotoxic necrotizing factor of Escherichia coli on HEp-2 cells was studied by fluorescence and scanning electron microscopy. This cytotoxin, known for inducing the formation of giant multinucleated cells in several cell lines, caused changes in actin and tubulin organization. The presence of membrane ruffles at the cell border and of numerous thick bundles of actin crossing the cell body, suggests that the factor promotes cell spreading; this probably interferes with cytokinesis, ultimately leading to the formation of very large flattened multinucleated cells. Moreover, the nuclear segmentation observed in treated cells seems to be associated with a rearrangement of actin in the perinuclear region and with the presence of tubulin bundles in proximity to nuclear clefts. Although the primary target is still unknown, these findings suggest that the cytoskeleton is affected accounting for the multinucleation process induced by the factor.


Clinical applications of computers in office practice.
The power to store and integrate vast amounts of information and to extract selected data rapidly makes the computer an obvious tool for physicians, particularly for family physicians, who attend to a large number of patients, deal with a great variety of problems, and provide comprehensive and long-term continuity of care. The ideal office computer system should be designed to permit each practice to select the business and clinical modules appropriate to that practice. The clinical modules would need to be sufficiently flexible to allow every physician to define the parameters he or she would wish to monitor for surveillance or health maintenance programs. There is an urgent need to arrive at some national consensus regarding the integration of clinical and business functions for office computers, particularly in family practice. Some pioneering physicians have shown the way. It now remains to translate the concepts into a generalizable system that would be suitable for a variety of settings.


Experimental Investigation on the Impact of Coal Fines Migration on Pores and Permeability of Cataclastic Coal.
During the production process of coalbed methane, the generation and migration of coal fines can obstruct fractures in coal reservoirs and reduce their permeability. In order to investigate the effects of coal fines migration on the porosity and permeability of coal reservoirs, we conducted core water flooding experiments, low-field nuclear magnetic resonance (NMR), and low-temperature N2 adsorption experiments to study the variations in porosity and permeability of cataclastic coal during coal fines migration and the impact of coal fines migration on porosity and permeability. The experimental results reveal that the initial porosity ratio of cataclastic coal exhibits the characteristics of micropore > macropore > transitional pore > mesopore, with the pore types being predominantly fissured. The porosity of pores larger than 1000 nm and those larger than 10,000 nm exhibit consistent trends before and after water flooding, indicating that the blockage or unblocking of pores with radius larger than 10,000 nm by coal fines can also cause blockage or unblocking of some interconnected macropore. The early stage of flooding is the main period for coal fines migration and production in cataclastic coal, during which the mass concentration of coal fines production is higher and some macropores and fractures become blocked, resulting in a larger decrease in porosity. The higher the initial permeability of cataclastic coal samples with a larger end-face fracture density, the more similar the variations in porosity and permeability of pores larger than 10,000 nm during the flooding experiment, indicating that coal fines mainly block interconnected pores and fractures with radius larger than 10,000 nm through migration, thereby reducing permeability. This study provides a theoretical basis for the efficient production of coalbed methane.


Impact of hyperprolactinemia in a patient with polyautoimmunity.
Hyperprolactinemia has been proposed as a triggering factor for autoimmune diseases. The increased levels of prolactin could induce an abnormal immune response. Herein, we present a patient with hyperprolactinemia who developed polyautoimmunity. Patient's symptoms were associated with slightly raised levels of prolactin (20-40 ng/mL) and administration of dopaminergic agonists.


Prevalence of human papillomavirus infection in esophageal and cervical cancers in the high incidence area for the two diseases from 2007 to 2009 in Linzhou of Henan Province, Northern China.
The etiological role of human papillomavirus (HPV) in cervical cancer has been well established. However, it is inconclusive whether HPV plays the same role in esophageal carcinogenesis. In this study, we detected HPV infection in 145 frozen esophageal tissues, including 30 normal epithelium (ENOR), 37 dysplasia (DYS) and 78 invasive squamous cell carcinoma (ESCC), and in 143 frozen cervical tissues composed of 30 normal epithelium (CNOR), 38 intraepithelial neoplasia (CIN) and 75 invasive squamous cell carcinoma (CSCC). The patients and symptom-free subjects enrolled in this study were from a high-incidence area for both ESCC and CSCC, Linzhou City, Northern China, from 2007 to 2009. The HPV infection analysis was conducted by using an HPV GenoArray Test Kit. We found that the high-risk HPV types accounted for more than 90 % of the HPV-positive lesions of esophagus and cervix tissues. The prevalence of high-risk HPV types increased significantly during the progression of both esophageal and cervical carcinogenesis (positive rate in esophageal tissues: 33 % ENOR, 70 % in DYS and 69 % in ESCC; positive rate in cervical tissues: 27 % in CNOR, 82 % in CIN and 88 % in CSCC; P < 0.001, respectively). Infection with the high-risk HPV types increased the risk for both DYS and ESCC by 4-fold (DYS vs. ENOR: OR = 4.73, 95 %CI = 1.68-13.32; ESCC vs. ENOR: OR = 4.50, 95 %CI = 1.83-11.05) and increased the risk for both CIN and CSCC by 12-fold and 20-fold (CIN vs. CNOR: OR = 12.18, 95 %CI = 3.85-38.55; CSCC vs. CNOR: OR = 20.17, 95 %CI = 6.93-58.65), respectively. The prevalence of high-risk types in ESCC patients was lower than that in CSCC patients (P = 0.005) and was significantly associated with the degree of ESCC tumor infiltration (P = 0.001). HPV 16 was the most prevalent subtype in both esophageal and cervical tissues. Single HPV infection increased significantly along with the progression of ESCC and maintained a high level in cervical tissues, regardless of whether they were CNOR or CSCC tissues. Our results showed that infection with HPV, especially the high-risk types, was positively associated with both esophageal and cervical cancers, suggesting that HPV also plays a role in the etiology of ESCC in the high-incidence area.


Associations between youth homelessness, sexual offenses, sexual victimization, and sexual risk behaviors: a systematic literature review.
Homeless youth commonly report engaging in sexual risk behaviors. These vulnerable young people also frequently report being sexually victimized. This systematic review collates, summarizes, and appraises published studies of youth investigating relationships between homelessness, perpetration of sexual offenses, experience of sexual victimization, and engagement in sexual risk behavior. A systematic search of seventeen psychology, health, and social science electronic databases was conducted. Search terms included "homeless*," "youth," "offend*," "victimization," "crime," "rape," "victim*," and "sex crimes." Thirty-eight studies were identified that met the inclusion criteria. Findings showed homeless youth commonly report being raped and sexually assaulted, fear being sexually victimized, and engage in street prostitution and survival sex. Rates of victimization and sexual risk behavior were generally higher for females. Given the paucity of longitudinal studies and limitations of current studies, it is unclear whether homelessness is prospectively associated with sexual victimization or engagement in sexual risk behavior, and whether such associations vary cross nationally and as a function of time and place. Future prospective research examining the influence of the situational context of homelessness is necessary to develop a better understanding of how homelessness influences the perpetration of sexual offenses, experience of sexual victimization, and engagement in sexual risk behavior among homeless youth.


Biphasic Formation of 2D Nanomembranes by Photopolymerization of Diacetylene Lipids as Revealed by Infrared Difference Spectroscopy.
Two-dimensional nanomembranes are promising materials for filtration or separation by providing the basis for controlled and rapid transport between two compartments. The polymerization by UV light of diacetylene-containing lipids at an interface produces free-standing 2D nanomembranes. Here, we analyzed in situ the nanomembrane formation of 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine (DiynePC) and 1-palmitoyl-2-(10,12-tricosadiynoyl)-sn-glycero-3-phosphoethanolamine (PTPE) on germanium using light-induced infrared difference spectroscopy with attenuated total reflection to obtain insights into the kinetics and mechanism of the polymerization process. Our interpretation is supported by atomic force microscopy and density functional theory. Formation of the polymer network is evidenced by changes in the frequency of C═O stretches acting as infrared probes. However, spectral and kinetic analysis revealed a biphasic process in the monolayer. In both phases, losses in signal of CH2 stretches are observed which are not in agreement with the accepted mechanism of chain propagation for diacetylene polymerization. These signals are dominant in the second phase and are assigned to termination reactions with some contributions from intramolecular consecutive reactions. This finding now provides a spectroscopic measure for the identity and integrity of the nanomembrane complementary to microscopic analysis. We deduce that limited 2D mobility on the solid support promotes intramolecular termination, leading to smaller domains.


Schwann cells and myasthenia gravis. Preferential uptake of soluble and membrane-bound AChR by normal and immortalized Schwann cells, and immunogenic presentation to AChR-specific T line lymphocytes.
The normal neuromuscular synapse is formed by the intimate association of nerve endings, postsynaptic end-plate foldings in the muscle fiber, and nonmyelinating Schwann cells (SC) sealing the synaptic ramifications. Because SC have been recognized recently to have an immunogenic potential inducible to present protein autoantigens to autoimmune T lymphocytes, and considering their close proximity to the acetylcholine receptor (AChR)-bearing postsynaptic membranes, presentation of soluble and membrane vesicle-bound AChR to appropriate T cells was investigated. Short-term monolayer cultures of SC isolated from neonatal rat sciatic nerves, as well as cells of an immortalized SC line of similar origin, were fully able to present the relevant molecular epitopes to major histocompatibility complex (MHC) compatible AChR-specific T line lymphocytes immunogenically. Presentation of AChR was restricted by RT1.B (I-A) MHC class II products. Both types of cultured rat SC were inducible to expression of MHC class I and II products, and they were able to phagocytose AChR-enriched membrane vesicles preferentially. In contrast, phagocytosis of latex particles by SC was negligible. These data qualify perisynaptic SC as potential presenter cells of autoimmunogenic AChR in myasthenia gravis. Thus, SC may play a critical and as-yet unpredicted regulatory role in the cellular pathogenesis of myasthenia gravis.


Scalability on roll-to-roll gravure printed dielectric layers for printed thin film transistors.
The manufacture of thin film transistors with reliable electrical properties, via full-printing on plastic foils, is a key step for the realization of costless and flexible electronics. To reach this goal, the dielectric layers should be smooth and free from failure while maintaining a high capacitance. In this paper, the parameters, affecting the film quality and capacitance of dielectric layers in a roll-to-roll gravure process, were investigated and some parameters were optimized.


Chronic opioid potentiates presynaptic but impairs postsynaptic N-methyl-D-aspartic acid receptor activity in spinal cords: implications for opioid hyperalgesia and tolerance.
Opioids are the most effective analgesics for the treatment of moderate to severe pain. However, chronic opioid treatment can cause both hyperalgesia and analgesic tolerance, which limit their clinical efficacy. In this study, we determined the role of pre- and postsynaptic NMDA receptors (NMDARs) in controlling increased glutamatergic input in the spinal cord induced by chronic systemic morphine administration. Whole-cell voltage clamp recordings of excitatory postsynaptic currents (EPSCs) were performed on dorsal horn neurons in rat spinal cord slices. Chronic morphine significantly increased the amplitude of monosynaptic EPSCs evoked from the dorsal root and the frequency of spontaneous EPSCs, and these changes were largely attenuated by blocking NMDARs and by inhibiting PKC, but not PKA. Also, blocking NR2A- or NR2B-containing NMDARs significantly reduced the frequency of spontaneous EPSCs and the amplitude of evoked EPSCs in morphine-treated rats. Strikingly, morphine treatment largely decreased the amplitude of evoked NMDAR-EPSCs and NMDAR currents of dorsal horn neurons elicited by puff NMDA application. The reduction in postsynaptic NMDAR currents caused by morphine was prevented by resiniferatoxin pretreatment to ablate TRPV1-expressing primary afferents. Furthermore, intrathecal injection of the NMDAR antagonist significantly attenuated the development of analgesic tolerance and the reduction in nociceptive thresholds induced by chronic morphine. Collectively, our findings indicate that chronic opioid treatment potentiates presynaptic, but impairs postsynaptic, NMDAR activity in the spinal cord. PKC-mediated increases in NMDAR activity at nociceptive primary afferent terminals in the spinal cord contribute critically to the development of opioid hyperalgesia and analgesic tolerance.


Glutamine prevents oxidative stress in a model of portal hypertension.
To evaluate the protective effects of glutamine in a model of portal hypertension (PH) induced by partial portal vein ligation (PPVL). Male Wistar rats were housed in a controlled environment and were allowed access to food and water ad libitum. Twenty-four male Wistar rats were divided into four experimental groups: (1) control group (SO) - rats underwent exploratory laparotomy; (2) control + glutamine group (SO + G) - rats were subjected to laparotomy and were treated intraperitoneally with glutamine; (3) portal hypertension group (PPVL) - rats were subjected to PPVL; and (4) PPVL + glutamine group (PPVL + G) - rats were treated intraperitoneally with glutamine for seven days. Local injuries were determined by evaluating intestinal segments for oxidative stress using lipid peroxidation and the activities of glutathione peroxidase (GPx), endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) after PPVL. Lipid peroxidation of the membrane was increased in the animals subjected to PH (P < 0.01). However, the group that received glutamine for seven days after the PPVL procedure showed levels of lipid peroxidation similar to those of the control groups (P > 0.05). The activity of the antioxidant enzyme GTx was decreased in the gut of animals subjected to PH compared with that in the control group of animals not subjected to PH (P < 0.01). However, the group that received glutamine for seven days after the PPVL showed similar GTx activity to both the control groups not subjected to PH (P > 0.05). At least 10 random, non-overlapping images of each histological slide with 200 × magnification (44 pixel = 1 μm) were captured. The sum means of all areas, of each group were calculated. The mean areas of eNOS staining for both of the control groups were similar. The PPVL group showed the largest area of staining for eNOS. The PPVL + G group had the second highest amount of staining, but the mean value was much lower than that of the PPVL group (P < 0.01). For iNOS, the control (SO) and control + G (SO + G) groups showed similar areas of staining. The PPVL group contained the largest area of iNOS staining, followed by the PPVL + G group; however, this area was significantly smaller than that of the group that underwent PH without glutamine (P < 0.01). Treatment with glutamine prevents gut mucosal injury after PH in rats.


Microbial Unmasking of Plant Glycosides.
The therapeutic potential of plants is widely recognized and harnessed in plant-based remedies and drug discovery. However, the factors that modulate the bioavailability and bioactivities of plant-derived phytochemicals are poorly understood. In a recent article in mBio, M. C. Theilmann et al. (mBio 8:e01421-17, 2017, https://doi.org/10.1128/mBio.01421-17) describe how one gut microbe, Lactobacillus acidophilus, catalytically unwraps plant glucosides to make deglucosylated bioactive aglycones available to human tissues. They demonstrate that understanding the metabolism of plant glycosides by intestinal bacteria is essential to appreciating how bacteria manipulate the levels of bioactive plant metabolites in the human host.


Optimization of production, purification and lyophilisation of cellobiose dehydrogenase by Sclerotium rolfsii.
The enzyme cellobiose dehydrogenase (CDH) can be used to oxidize lactose to lactobionic acid. As Sclerotium rolfsii is known to be a good producer of CDH, the aim of this paper was to simplify its production and secondly to systematically study its purification aiming for a high yield. Two preservation methods (freezing and freeze-drying) and the influence of several protectants were investigated. Production of cellobiose dehydrogenase was optimized leading to a more simplified medium composition. Purification of the enzyme was evaluated by determining breakthrough profiles on different ion exchange (IEX) and hydrophobic interaction (HIC) materials with regard to buffer composition. Highest purification with an acceptable loss during the capture step using IEX was obtained with a Q Sepharose XL medium and a 100 mM sodium acetate buffer at pH 4.5. Subsequent purification using hydrophobic interaction chromatography was done at 1.1 M ammonium sulfate concentration. Purification was moderate, yielding a specific activity of 11.9 U/mg (56% yield). However, as could be shown in a preliminary experiment, purity of the obtained enzyme solution was sufficient for its intended use to oxidize lactose to lactobionic acid. Various sugars and sugar alcohols were investigated to study their protective effect during lyophilisation and freezing at -20 °C. Glucose and lactulose could be identified to have a high lyoprotective effect while loss of enzyme activity was high (77%) when using no additives. By simplifying the cultivation medium of Sclerotium rolfsii, the costs of cellobiose dehydrogenase production could be reduced. Simultaneously, CDH production was increased by 21%. The production of lactobionic acid from lactose is possible using partially purified and unpurified enzyme. Storage at -20 °C using 50% (w/v) glycerol was considered to be most suited for preservation of the enzyme.


Antiatherosclerotic and antioxidative effects of captopril in apolipoprotein E-deficient mice.
The effect of the angiotensin-converting enzyme (ACE) inhibitor, captopril, on the development of atherosclerosis was determined in the apolipoprotein (apo) E-deficient mice. These mice develop severe hypercholesterolemia and extensive atherosclerotic lesions on chow diet, similar to those found in humans. Furthermore, in these mice, accelerated atherosclerosis is associated with increased plasma lipid peroxidation, a phenomenon that may play a crucial role in the buildup of the atherosclerotic lesions. Mice received either placebo or 50 mg/kg/day of captopril. After 12 weeks of treatment, captopril reduced the aortic-lesion area by 70% compared with that of the placebo-treated group. Captopril also increased the resistance of low-density lipoprotein (LDL) to CuSO4-induced oxidative stress, as shown by a significant reduction in the LDL content of malondialdehyde (MDA) by 30%, as well as by the prolongation of the lag time required for LDL oxidation from 55 min in the placebo-treated mice to 70 min in the captopril-treated mice, and reduction of the maximum LDL oxidation at 150 min by 35%. In vitro studies demonstrated that preincubation of LDL with captopril, inhibited the onset of CuSO4-induced LDL peroxidation up to 120 min, and reduced the LDL content of MDA by 90%. We conclude that captopril attenuates atherosclerosis in the apo E-deficient mice, and this phenomenon may be related to its inhibitory effect on the plasma LDL oxidation.


Alterations of the thymus and other lymphoid tissue in young horses with combined immunodeficiency.
Combined immunodeficiency (CID) is a significant disease in terms of prevalence in Arabian foals and is a useful animal for study of a similar condition in children. Thymuses from all CID foals examined were extremely hypoplastic. Light and electron microscopic examination of thymuses from CID foals, as well as a thymus from an aborted CID fetus, demonstrate that the basic thymic structure is intact, despite a number of dissimilar morphologic appearances. From these data, we inferred that the thymic hypoplasia was caused by a failure of committed lymphocytes from the bone marrow to populate the organ. The lack of uniform organized lymphocytes in the spleen and lymph nodes provides considerable support for the absence of lymphoid precursors or their inability to respond to differentiating influences.


Molecular genetic characterization of epitope-specific monoclonal antibodies against the myc family proteins.
The myc family proteins were used to produce monoclonal antibodies with defined specificities. The pattern of mosaic homology among the myc family proteins facilitated the efficient identification of monoclonal antibodies specific to myc homology box sequences. Sequential epitopes for pan-myc reactive monoclonal antibodies produced against N-myc/c-myc fusion protein were further defined by use of truncated myc proteins made in E. coli and synthetic oligopeptides corresponding to myc box sequences. One class of antibodies was found to be specific to the first myc box sequence, whereas the other was found to be reactive with the third myc box sequence. Further development of anti-myc monoclonal antibodies, especially those antibodies specific to each myc box sequence, would be likely to facilitate analysis of the possible biological functions of the myc proteins in vivo and in vitro.


[Is our management of patients with claudicatio intermittens correct?].
Claudicatio intermittens is the major symptom of peripheral arterial disease of extremities. At the same time it is an important manifestation of systemic atherosclerosis. In spite of the fact that the diagnosis of claudicatio intermittens requires only simple, non-invasive, and inexpensive diagnostic methods, the disease is still underdiagnosed and often goes untreated. Proper treatment of patients with claudicatio intermittens prevents the progression of the disease and development of critical limb ischemia as well as reduces other complications of systemic atherosclerosis, including cardiovascular death.


Prevalence and associated factors of hypertension: results from a three community-based survey, Jordan.
The aim of this study was to estimate the prevalence of hypertension, to determine its association with certain cardiovascular disease risk factors, and to evaluate level of hypertension awareness and control in an adult population in Jordan. The study used a cross-sectional population survey of a systematic sample of three communities. Data for the sample of 2299 adults, aged 25 years and older, were collected from September 1994 to September 1995. A total of 370 subjects or 16.1% were found to have hypertension. The prevalence rate was higher among women (17.1%) than men (14.4%). Logistic regression analysis indicated that hypertension was positively associated with gender, age, family history of hypertension, diabetes mellitus, and total serum cholesterol, but negatively associated with level of education. No association between hypertension and smoking was detected in this study. About one-half (48.6%) of hypertensives in this study were unaware of their diagnosis. Awareness of hypertension was positively associated with age and family history. More than one-third (36.5%) of those aware of their diagnosis did not achieve control of their hypertension. Hypertension appears to be a common public health problem in Jordan. Awareness and control of hypertension are far below optimal levels.


Predictive factors of early mortality after percutaneous endoscopic gastrostomy placement: The importance of C-reactive protein.
Percutaneous endoscopic gastrostomy (PEG) is considered one of the preferred routes for long-term enteral feeding. However, early mortality after PEG placement is high. We aimed at analyzing overall and early mortality in patients who underwent PEG insertion and at identifying risk factors of increased mortality after the procedure. Retrospective study which included patients who had a PEG insertion at our department between May 2007 and January 2013. Variables analyzed: demographic, Charlson's co-morbidity index, past aspiration pneumonia, indication for PEG, hemogram, ionogram, urea, creatinine, albumin and C-reactive protein (CRP). death. Kaplan-Meier survival analysis was used to calculate mortality after PEG placement. Predictive factors of overall mortality were identified by univariate and multivariate analysis and of 30-day, 90-day and 180-day mortality by logistic regression. The AUROC analysis for CRP levels was performed. Inclusion of 135 patients: 51.9% female, mean age of 73 ± 17 years, 90.4% with neurological dysphagia and 9.6% with tumors compromising oral intake. The median survival time was 272 days. The 30-day, 90-day and 180-day mortality was 0.14 ± 0.06 (95% CI 0.08-0.20), 0.29 ± 0.08 (95% CI 0.21-0.37) and 0.43 ± 0.08 (95% CI 0.35-0.51), respectively. Patients with higher levels CPR (hazard ratio (HR) 1.009 95% CI 1.002-1.160, p = 0.012) and higher levels of urea (HR 1.009 95% CI 1.002-1.160, p = 0.012) had worse outcome and those with higher sodium levels (HR 0.945 95% CI 0.908-0.983, p = 0.005) had better prognosis. Higher CRP levels was the only independent predictive factor for 30-day mortality (odds ratio (OR) 1.008 95% CI 1.001-1.014, p = 0.029), and was also a risk factor for 90-day and 180-day mortality (OR 1.013 95% CI 1.005-1.021, p = 0.002 and OR 1.009 95% CI 1.001-1.018, p = 0.026, respectively). CRP levels ≥35.9 mg/dL could predict death at 30 days with a sensitivity of 0.810 and a specificity of 0.614. The early mortality after PEG placement is high. CRP, an indicator of acute illness, is a useful parameter at identifying patients with increased probability of dying after PEG insertion. High CRP levels should be considered in the decision making process.


Pay as You Speed, ISA with incentive for not speeding: results and interpretation of speed data.
To simulate a market introduction of Intelligent Speed Adaptation (ISA) and to study the effect of a Pay as You Speed (PAYS) concept, a field trial with 153 drivers was conducted during 2007-2009. The participants drove under PAYS conditions for a shorter or a longer period. The PAYS concept consisted of informative ISA linked with economic incentive for not speeding, measured through automatic count of penalty points whenever the speed limit was exceeded. The full incentive was set to 30% of a participant's insurance premium. The participants were exposed to different treatments, with and without incentive crossed with informative ISA present or absent. The results showed that ISA is an efficient tool for reducing speeding particularly on rural roads. The analysis of speed data demonstrated that the proportion of distance driven above the speed where the ISA equipment responded (PDA) was a sensitive measure for reflecting the effect of ISA, whereas mean free flow speed and the 85th percentile speed, were less sensitive to ISA effects. The PDA increased a little over time but still remained at a low level; however, when ISA was turned off, the participants' speeding relapsed to the baseline level. Both informative ISA and incentive ISA reduced the PDA, but there was no statistically significant interaction. Informative reduced it more than the incentive.


Decreased T1 contrast between gray matter and normal-appearing white matter in CADASIL.
CADASIL is the most frequent hereditary small-vessel disease of the brain. The clinical impact of various MR imaging markers has been repeatedly studied in this disorder, but alterations of contrast between gray matter and normal-appearing white matter remain unknown. The aim of this study was to evaluate the contrast alterations between gray matter and normal-appearing white matter on T1-weighted images in patients with CADASIL compared with healthy subjects. Contrast between gray matter and normal-appearing white matter was assessed by using histogram analyses of 3D T1 high-resolution MR imaging in 23 patients with CADASIL at the initial stage of the disease (Mini-Mental State Examination score > 24 and modified Rankin scale score ≤ 1; mean age, 53.5 ± 11.1 years) and 30 age- and sex-matched controls. T1 contrast between gray matter and normal-appearing white matter was significantly reduced in patients compared with age- and sex-matched controls (patients: 1.35 ± 0.08 versus controls: 1.43 ± 0.04, P < 10(-5)). This reduction was mainly driven by a signal decrease in normal-appearing white matter. Contrast loss was strongly related to the volume of white matter hyperintensities. Conventional 3D T1 imaging shows significant loss of contrast between gray matter and normal-appearing white matter in CADASIL. This probably reflects tissue changes in normal-appearing white matter outside signal abnormalities on T2 or FLAIR sequences. These contrast alterations should be taken into account for image interpretation and postprocessing.


Statin Use Reduces Prostate Cancer All-Cause Mortality: A Nationwide Population-Based Cohort Study.
Studies have suggested that statin use is related to cancer risk and prostate cancer mortality. We conducted a population-based cohort study to determine whether using statins in prostate cancer patients is associated with reduced all-cause mortality rates. Data were obtained from the Taiwan National Health Insurance Research Database. The study cohort comprised 5179 patients diagnosed with prostate cancer who used statins for at least 6 months between January 1, 1998 and December 31, 2010. To form a comparison group, each patient was randomly frequency-matched (according to age and index date) with a prostate cancer patient who did not use any type of statin-based drugs during the study period. The study endpoint was mortality. The hazard ratio (HR) and 95% confidence interval (CI) were estimated using Cox regression models. Among prostate cancer patients, statin use was associated with significantly decreased all-cause mortality (adjusted HR = 0.65; 95% CI = 0.60-0.71). This phenomenon was observed among various types of statin, age groups, and treatment methods. Analyzing the defined daily dose of statins indicated that both low- and high-dose groups exhibited significantly decreased death rates compared with nonusers, suggesting a dose-response relationship. The results of this population-based cohort study suggest that using statins reduces all-cause mortality among prostate cancer patients, and a dose-response relationship may exist.


Histological, immunohistological and molecular characteristics of intraductal precursor of carcinoma ex pleomorphic adenoma support a multistep carcinogenic process.
In recent years, multistep carcinogenesis of carcinoma ex pleomorphic adenoma (CEPA) has been identified, starting with intraductal neoplasia within pre-existent pleomorphic adenoma (PA). However, as yet there is no consensus regarding clinical relevance and appropriate terminology of precursor lesions in CEPA. We therefore decided to investigate precursor lesions, especially intraductal carcinoma, in a series of 85 cases of CEPA. Intraductal carcinoma confined by benign myoepithelial cells was found in 60 cases and mostly exhibited high-grade cellular atypia, increased cellular proliferation and frequent genetic alterations (TP53, Her2-neu, androgen receptor). Intraductal carcinoma was absent only in the myoepithelial type of CEPA. In 26 cases, purely intraductal CEPA with extensive intraductal expansion was found. This suggests that there is a long period of intraductal growth before extraductal intracapsular infiltration of the PA. We identified two different histomorphological types of intraductal carcinoma, which we call 'clinging' and 'solid' types. In summary, combined histological, immunohistological and molecular data strongly support multistep carcinogenesis starting with intraductal carcinoma for all non-myoepithelial types of CEPA. The clinical significance of our finding of two histomorphological types of intraductal carcinoma (clinging and solid) is not yet clear. Intraductal carcinoma, intracapsular invasive CEPA and minor extracapsular invasive CEPA (up to about 6 mm) all show favourable prognosis and together comprise half of the cases in our study.


Membrane-active compounds activate the transcription factors Pdr1 and Pdr3 connecting pleiotropic drug resistance and membrane lipid homeostasis in saccharomyces cerevisiae.
The Saccharomyces cerevisiae zinc cluster transcription factors Pdr1 and Pdr3 mediate general drug resistance to many cytotoxic substances also known as pleiotropic drug resistance (PDR). The regulatory mechanisms that activate Pdr1 and Pdr3 in response to the various xenobiotics are poorly understood. In this study, we report that exposure of yeast cells to 2,4-dichlorophenol (DCP), benzyl alcohol, nonionic detergents, and lysophospholipids causes rapid activation of Pdr1 and Pdr3. Furthermore, Pdr1/Pdr3 target genes encoding the ATP-binding cassette proteins Pdr5 and Pdr15 confer resistance against these compounds. Genome-wide transcript analysis of wild-type and pdr1Delta pdr3Delta cells treated with DCP reveals most prominently the activation of the PDR response but also other stress response pathways. Polyoxyethylene-9-laurylether treatment produced a similar profile with regard to activation of Pdr1 and Pdr3, suggesting activation of these by detergents. The Pdr1/Pdr3 response element is sufficient to confer regulation to a reporter gene by these substances in a Pdr1/Pdr3-dependent manner. Our data indicate that compounds with potential membrane-damaging or -perturbing effects might function as an activating signal for Pdr1 and Pdr3, and they suggest a role for their target genes in membrane lipid organization or remodeling.


A model of speech recognition for hearing-impaired listeners based on deep learning.
Automatic speech recognition (ASR) has made major progress based on deep machine learning, which motivated the use of deep neural networks (DNNs) as perception models and specifically to predict human speech recognition (HSR). This study investigates if a modeling approach based on a DNN that serves as phoneme classifier [Spille, Ewert, Kollmeier, and Meyer (2018). Comput. Speech Lang. 48, 51-66] can predict HSR for subjects with different degrees of hearing loss when listening to speech embedded in different complex noises. The eight noise signals range from simple stationary noise to a single competing talker and are added to matrix sentences, which are presented to 20 hearing-impaired (HI) listeners (categorized into three groups with different types of age-related hearing loss) to measure their speech recognition threshold (SRT), i.e., the signal-to-noise ratio with 50% word recognition rate. These are compared to responses obtained from the ASR-based model using degraded feature representations that take into account the individual hearing loss of the participants captured by a pure-tone audiogram. Additionally, SRTs obtained from eight normal-hearing (NH) listeners are analyzed. For NH subjects and three groups of HI listeners, the average SRT prediction error is below 2 dB, which is lower than the errors of the baseline models.


Treatment of chronic Hepatitis C in Thalassemia major patients.
Treatment of chronic hepatitis C (HCV) is difficult in thalassemics due to the haemolytic side effects of therapy. This study evaluated the treatment response to conventional interferon and ribavirin in HCV patients with thalassemia major. It was conducted at PMRC Research Centre, Jinnah Postgraduate Medical Centre (JPMC) Karachi. At baseline complete blood count, liver function tests, serum protein/ albumin, random blood glucose, serum ferritin, TSH, HCV RNA (quantitative) and genotyping were done. Conventional interferon 3 MIU thrice weekly and ribavirin 400 mg daily was given for 24 or 48 weeks. HCV RNA was done at 1st month (RVR), 3rd month (EVR), 6th month (ETR) and six months post treatment sustained virological response (SVR). A total of 17 Anti HCV positive patients, age range 7-28 years were included.HCV RNA was found in 12. Treatment was completed in 8 patients. Genotype 3(87.5%) was found in 7 patients, 1 had genotype 1. RVR was achieved in 5 (62.5%) cases, negative PCR at 3 and 6 months of treatment (EVR) in 7 (87.5%) patients, one patient was non responder. SVR was achieved in 2(25%) patients. Anaemia was the most common side effect due to which transfusion requirements increased in 4(50%) patients.


Intervention research: establishing fidelity of the independent variable in nursing clinical trials.
Internal validity of a randomized clinical trial of a nursing intervention is dependent on intervention fidelity. Although several methods have been developed, evaluating audio or audiovisual tapes for prescribed and proscribed interventionist behaviors is considered the gold standard test of treatment fidelity. This approach requires development of a psychometrically sound instrument to meaningfully categorize and quantify interventionist behaviors. To outline critical steps necessary to develop a treatment fidelity instrument. A comprehensive literature review was conducted to determine procedures used by other researchers. The literature review produced five quantitative studies of treatment fidelity, all in the field of psychotherapy, and two replication studies. A synthesis of methodologies across studies combined with researchers' experiences resulted in identification of the steps necessary to develop a treatment fidelity measure. Seven sequential steps were identified as essential to the development of a valid and reliable measure of treatment fidelity. These steps include (a) identification of the essential elements of the experimental and control treatment modalities; (b) construction of scale items; (c) development of item scaling; (d) identification of the units for coding; (e) item testing and revision; (f) specification of rater qualifications and development of rater training program; and (g) development and completion of pilot testing to test psychometric properties. Development of the Possibilities Project Psychotherapy Coding Questionnaire is described as an illustration of the seven-step process. The results show the essential steps that are unique to the development of treatment fidelity measures and show the feasibility of using these steps to construct a psychometrically sound treatment-specific fidelity measure.


Application of bacteriophages for the inactivation of Salmonella spp. in biofilms.
Microbial biofilms pose a serious threat to food industry, as they are difficult to inactivate or remove owing to their inherent resistance to traditional physical and antimicrobial treatments. Bacteriophages have been suggested as promising biocontrol agents for eliminating biofilms within the food industry. The efficacy of phages (BP 1369 and BP 1370) was evaluated against Salmonella spp. in biofilms. Biofilms were grown on food (lettuce), food contact surfaces (stainless steel and rubber), and MBEC biofilm devices. The efficacy of these phages in reducing biofilms was examined following phage (108 PFU/mL) treatment for 2 h. Bacteriophage treatment reduced biofilm cells by 3.0, 2.0, and 3.0 log CFU/cm2 on stainless steel, rubber, and an MBEC device, respectively. The adhered viable cells on lettuce were reduced by more than 1.0 log CFU/cm2 with phage treatment.


Large area IR microlens arrays of chalcogenide glass photoresists by grayscale maskless lithography.
The ability to use chalcogenide glass thin films as photoresists for one-step maskless grayscale lithographic patterning is demonstrated. It is shown that the chalcogenide photoresists can be used to fabricate grayscale patterns with smooth and continuous profiles such as arrays of cylindrical and spherical microlenses, which are useful as optical structures for IR applications. The etching and exposure parameters are optimized to obtain smooth reproducible lens arrays of 150 μm periodicity and up to ∼170 nm height on large areas (∼1 cm(2)). The roughness is found to increase as a function of the exposure dose and is attributed to the selective dissolution of the As-Se, As-As, and Se-Se bonds present in the nanodistributed phases and the presence of the oxide phase. Thus, a minimum exposure dose produces optimally patterned lens arrays. The focal length calculated for the smooth microlens array is ∼9.3 mm, indicating the suitability of the lens arrays for focusing applications in the IR region.


Lay public mental models of ionizing radiation: representations and risk perception in four European countries.
How do members of the lay public understand ionizing radiation and its effects? How do they define ionizing radiation, and to which other concepts do they connect it? Do they perceive danger and risks? Do they know how to protect themselves? What do they think of various applications of ionizing radiation? Where and how does the public lodge confidence or doubt? What is the demand for information and transparency? We applied the mental models approach to investigate these questions in four European countries (France, Poland, Romania, and Slovenia; 63 respondents), providing a rich picture of how the lay public perceives ionizing radiation. Mental models are messy and overlapping but meaningful and useful schemas, resulting from a person's multidimensional experience and relation to the surrounding natural and social world. Collectively, members of the lay public (independently of their education or background) possess a non-negligible amount of knowledge on the topic of ionizing radiation risk, and hold strong views on related concepts. Mutual understanding between specialists and potentially affected citizens may be a critical pathway to build a shared and effective risk culture supported by accurate, two-way risk communication and inter-actor relationships.


Concomitant radiotherapy with protracted 5-fluorouracil infusion in locally advanced carcinoma of the pancreas: a phase II study.
To evaluate the efficacy of combined radiation therapy and continuous infusion of 5-fluorouracil in patients with locally advanced carcinoma of the pancreas. Between January 1992 and June 1999, 31 patients with locally advanced adenocarcinoma of the pancreas were treated in our Institute. In 20 patients, the tumor (65%) was located in the head of the pancreas and in 11 (35%) in the body or tail; 13 cases also showed involved nodes. Radiation therapy consisted in a median dose of 63 Gy in 33-36 fractions applied to the tumor and regional lymph nodes. Chemotherapy with 5-fluorouracil in continuous infusion, 250 mg/m2 daily, was administered in the first and fifth week of the radiation therapy. Thereafter, 22 patients received 3-10 cycles of adjuvant chemotherapy with same doses. Median follow-up of the series was 20 months. The toxicity of the treatment was scored according to WHO criteria. All patients underwent nutritional assessment at the time of radiochemotherapy. The median overall survival was 15.2 months (range, 4-42). At restaging, 17 cases (55%) showed no change and 14 (45%) a partial remission. At the end of radiochemotherapy in 8 (26%) of the cases there was indication for pancreatectomy, which was executed in 4 patients. At the time of the study, 2 patients (6.4%) were surgically proven disease free. Eleven of the 13 cases (85%) presenting involved nodes showed that the enlarged lymph nodes had disappeared. Nineteen patients (61%) are alive with clinical evidence of disease anti 2 cases are alive with liver metastases; 8 patients (26%) died for disease. In 74% of cases there was complete pain control. Tolerance to the regimen was good. Nutritional assistance was evaluated and was found to be correlated to survival. The results of the series confirm a good tolerance with low acute toxicity. Tumor down-staging and resectability rates were high, together with prolonged survival and a good quality of life.