Signs of ROS-Associated Autophagy in Testis and Sperm in a Rat Model of Varicocele.
Since autophagy was suspected to occur in the pathological situation of varicocele (VCL), we have attempted to confirm it here using a surgical model of varicocele-induced rats. Thirty Wistar rats were divided into three groups (varicocele/sham/control) and analyzed two months after the induction of varicocele. Testicular tissue sections and epididymal mature sperm were then monitored for classic features of varicocele, including disturbance of spermatogenesis, impaired testicular carbohydrate and lipid homeostasis, decreased sperm count, increased sperm nuclear immaturity and DNA damage, oxidative stress, and lipid peroxidation. At the same time, we evaluated the Atg7 protein content and LC3-II/LC3-1 protein ratio in testis and mature sperm cells, two typical markers of early and late cellular autophagy, respectively. We report here that testis and mature sperm show higher signs of autophagy in the varicocele group than in the control and sham groups, probably to try to mitigate the consequences of VCL on the testis and germ cells.


Selenium increases hydrogenase expression in autotrophically cultured Bradyrhizobium japonicum and is a constituent of the purified enzyme.
We have investigated the effect of added selenite on autotrophic growth and the time course of hydrogen oxidation derepression in Bradyrhizobium japonicum 122DES cultured in a medium purified to remove selenium compounds. In addition, hydrogenase was purified to near homogeneity and examined for the specific incorporation of Se into the enzyme. The addition of Se at 0.1 microM significantly increased total cell protein and hydrogenase specific activity of harvested cells. Also, the addition of SeO3(2-) enhanced the time course of hydrogenase derepression by 133%, whereas VO3, AsO2(2-), SO2(2-), and TeO3(2-) failed to substantially affect hydrogenase derepression. During the final chromatographic purification of hydrogenase, a striking coincidence in peaks of protein content, Se radioactivity, and hydrogenase activity of fractions was obtained. The total Se content expressed per milligram of protein increased manyfold during the purification procedure. The mean Se content of the purified hydrogenase was 0.56 +/- 0.13 mol of Se per mol of enzyme. These results indicate that Se is an important element in the H2 metabolism of B. japonicum and that hydrogenase from B. japonicum is a seleno protein.


Determining the Potential of Mean Force for Amyloid-β Dimerization: Combining Self-Consistent Field Theory with Molecular Dynamics Simulation.
Amyloid-β (Aβ) protein aggregates through a complex pathway to progress from monomers to soluble oligomers and ultimately insoluble fibrils. Because of the dynamic nature of aggregation, it has proven exceedingly difficult to determine the precise interactions that lead to the formation of transient oligomers. Here, a statistical thermodynamic model has been developed to elucidate these interactions. Aβ1-42 was simulated using fully atomistic replica exchange molecular dynamics. We use an ensemble of approximately 5 × 105 configurations taken from simulation as input in a self-consistent field theory that explicitly accounts for the size, shape, and charge distribution of both the amino acids comprising Aβ and all molecular species present in solution. The solution of the model equations provides a prediction of the probabilities of the configurations of the Aβ dimer and the potential of mean force between two monomers during the dimerization process. This model constitutes a reliable methodology to elucidate the underlying physics of the Aβ dimerization process as a function of pH, temperature, and salt concentration. The results obtained with this new model could be valuable in the design of Aβ oligomerization inhibitors, a prospective therapeutic for Alzheimer's disease.


Safety of available and emerging drug therapies for hyperhidrosis.
Hyperhidrosis affects 4.8% of the U.S. population and has been underestimated by physicians for long time despite considerable interference with quality of life. Many patients suffer from primary (idiopathic) hyperhidrosis which results from over-activity of sympathetic nerves and is restricted to specific body areas, mostly the axillae, palms, soles, or head. Secondary hyperhidrosis is caused by an underlying disease or the intake of medications and often involves large parts of the body. Numerous effective therapies with topical or systemic drugs and surgical options are available. Areas covered: Efficacy and safety data on aluminum salts, anticholinergic drugs for topical or systemic application, and on intradermal botulinum toxin injections used to treat hyperhidrosis are critically evaluated, including data from clinical trials with focus on possible side effects and long-term complications in dispute. Expert opinion: Hyperhidrosis often responds well to available therapies. Depending on the type of hyperhidrosis treatment should be topical/local or systemic. Most of the side effects are mild, transient and easily manageable. In case of systemic treatment with anticholinergics low dosing and up-titration of medication is necessary to avoid severe adverse effects. Concerns about the promotion of breast cancer and Alzheimer disease by topical aluminum salts are unsolved.


The peripheral hemodynamic effects of continuous positive transpulmonary pressure breathing in neonates free from cardiorespiratory disease.
We applied continuous positive transpulmonary pressure (CPTP) by face mask to 22 spontaneously breathing infants who were free from cardiorespiratory disease, and measured resultant changes in peak esophageal pressure (Pes) and peripheral perfusion (Q1). We measured Pes by balloon and transducer, and Q1 by venous occlusion plethysmography with a mercury-in-rubber strain gauge. Application of 7.6 cm H2O CPTP led to a 13% decrease in Q1 (paired t-test=2.39; P less than .02). Thirty-two percent of the applied CPTP was detected as a change in Pes. The biological significance of a 13% decrease in peripheral perfusion is probably minimal.


Paniculacin, a new coumarin derivative from Murraya paniculata.
Paniculacin (1), a new coumarin derivative, has been isolated from the ethyl acetate soluble fraction of the ethanolic extract of Murraya paniculata along with umbelliferone, scopoletin, 4-hydroxybenzoic acid, trans-cinnamic acid, and β-sitosterol. Their structures were elucidated on the basis of spectral data.


Investigation on water status and distribution in broccoli and the effects of drying on water status using NMR and MRI methods.
Many quality attributes of food products are influenced by the water status and the microstructure. Low-field nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) methods are applied to non-destructively monitor the water status and structure of food. The aim of this study is to investigate the water status and distribution inside broccoli tissues and the effects of hot-air drying on the water status by using NMR and MRI methods. Transverse relaxation times (T2) provide the information of water status and water distribution. Results show that three water fractions with different T2 relaxation times were detected inside broccoli, which corresponded to different cell compartments. Proton weighted imaging could monitor the spatial distribution of water. Image analysis indicates that the water distribution inside broccoli was heterogeneous and the water content reduced from the stalk to the buds. During hot-air drying experiments, different drying kinetics were observed in the florets and stalks, which were related to their different structures. In addition, a detection limit of the moisture content was calculated for LF-NMR (about 11.35%). The results of this study show that the low-field NMR and MRI methods can precisely provide the quantitative information of water status inside food materials, and can be used to investigate the effects of food processing on product quality. The method provided in this study can be used to monitor changes of water status and distribution in a sample non-destructively during drying process.


Measurement and Clinical Significance of Biomarkers of Oxidative Stress in Humans.
Oxidative stress is the result of the imbalance between reactive oxygen species (ROS) formation and enzymatic and nonenzymatic antioxidants. Biomarkers of oxidative stress are relevant in the evaluation of the disease status and of the health-enhancing effects of antioxidants. We aim to discuss the major methodological bias of methods used for the evaluation of oxidative stress in humans. There is a lack of consensus concerning the validation, standardization, and reproducibility of methods for the measurement of the following: (1) ROS in leukocytes and platelets by flow cytometry, (2) markers based on ROS-induced modifications of lipids, DNA, and proteins, (3) enzymatic players of redox status, and (4) total antioxidant capacity of human body fluids. It has been suggested that the bias of each method could be overcome by using indexes of oxidative stress that include more than one marker. However, the choice of the markers considered in the global index should be dictated by the aim of the study and its design, as well as by the clinical relevance in the selected subjects. In conclusion, the clinical significance of biomarkers of oxidative stress in humans must come from a critical analysis of the markers that should give an overall index of redox status in particular conditions.


Bile acid deconjugation and attachment of chicken gut bacteria: their possible role in growth depression.
Bacteria isolated from the chicken gut were tested for their ability to deconjugate bile acids and attach to chicken epithelial cells (crop squamous cells and duodenal brush borders). Clostridium perfringens, streptococci and some of the bifidobacteria and lactobacilli were able to deconjugate all 4 substrates whereas the bacteroides deconjugated only the taurine conjugates and the coliforms were completely inactive. None of the strains of Escherichia coli or streptococci attached to squamous cells, but the anaerogenic coliform, the strain of Klebsiella aerogenes and the lactobacilli did show attachment. Attachment to brush borders was obtained with the anaerogenic coliforms, K. aerogenes, 2 out of 5 of the lactobacilli, and 4 out of 9 of the streptococci, but none of the strains of E. coli.


Endoscopic trans-sphenoidal surgery for petroclival and clival meningiomas.
Petroclival meningiomas are challenging lesions to manage independently of the selected surgical approach and are unique tumors in the type of pathological displacement of the surrounding anatomy. They also represent one of the most controversial entities with regard to approach selection, especially when deciding between an open versus endonasal route. When choosing an approach to the intradural portion of the petroclival region, the location of critical neurovascular structures relative to the lesion must be anticipated, including the abducens and trigeminal nerves. The role of the expanded endoscopic endonasal approach (EEA) in the management of ventral posterior fossa meningiomas is still restricted due to limited surgical indications in selected cases. It is a safe alternative for the rare cases of meningiomas with most part of its dural base at the midline clival region, and it may be used as solely or combination of other approaches. Thus, appropriate case selection may optimize the advantages of the approach and reduce morbidity of this complex pathology. We discuss in this review article the main advantages and limitations of the EEA for clival and petroclival meningiomas.


Surgical aortic valve replacement and patient-prosthesis mismatch: a meta-analysis of 108 182 patients.
This study sought to evaluate the impact of patient-prosthesis mismatch (PPM) on the risk of perioperative, early-, mid- and long-term mortality rates after surgical aortic valve replacement. Databases were searched for studies published until March 2018. The main outcomes of interest were perioperative mortality, 1-year mortality, 5-year mortality and 10-year mortality. The search yielded 3761 studies for inclusion. Of these, 70 articles were analysed, and their data were extracted. The total number of patients included was 108 182 who underwent surgical aortic valve replacement. The incidence of PPM after surgical aortic valve replacement was 53.7% (58 116 with PPM and 50 066 without PPM). Perioperative mortality [odds ratio (OR) 1.491, 95% confidence interval (CI) 1.302-1.707; P < 0.001], 1-year mortality (OR 1.465, 95% CI 1.277-1.681; P < 0.001), 5-year mortality (OR 1.358, 95% CI 1.218-1.515; P < 0.001) and 10-year mortality (OR 1.534, 95% CI 1.290-1.825; P < 0.001) were increased in patients with PPM. Both severe PPM and moderate PPM were associated with increased risk of perioperative mortality, 1-year mortality, 5-year mortality and 10-year mortality when analysed together and separately, although we observed a higher risk in the group with severe PPM. Moderate/severe PPM increases perioperative, early-, mid- and long-term mortality rates proportionally to its severity. The findings of this study support the implementation of surgical strategies to prevent PPM in order to decrease mortality rates.


Low-Risk Gestational Trophoblastic Neoplasia in Manitoba: Experience With Alternating Methotrexate and Dactinomycin.
The aim of this study was to review the treatment and outcomes of low-risk gestational trophoblastic neoplasia (GTN) in Manitoba over more than 3 decades, with a focus on those treated with alternating methotrexate and dactinomycin, a protocol that has only rarely been described. We retrospectively reviewed all patients with GTN referred to CancerCare Manitoba from January 1977 to December 2012. Cases were classified as low risk as per the modified WHO-FIGO prognostic scoring system (score, ≤6). Demographic, treatment, and outcomes data were abstracted, and descriptive statistics and time-to-event analysis were performed. The low-risk protocol used at CancerCare Manitoba consists of alternating single-agent use of methotrexate and dactinomycin, each for 5 days, on a 14-day cycle. Sixty-seven cases of GTN were identified, of which 52 were low risk. Thirty-nine patients were initiated on alternating methotrexate and dactinomycin. Thirty-four (87.2%) achieved primary cure on this regimen, with a median of 4.4 cycles administered (range, 2-7). Median time to response was 56 days. One patient achieved cure after receiving a repeat course of methotrexate as their final cycle. Second-line multiagent chemotherapy was required by 4 patients. Two patients experienced grade 3 toxicities, and none greater than grade 3. There were no recurrences. Alternating methotrexate and dactinomycin is an effective treatment protocol for low-risk GTN, with high rates of primary cure and acceptable toxicity.


UW is superior to Celsior and HTK in the protection of human liver endothelial cells against preservation injury.
Celsior solution (CS), a new preservation solution in thoracic organ transplantation, was evaluated for its efficacy in cold preservation of human liver endothelial cells (HLEC) and was compared to University of Wisconsin solution (UW) and histidine-tryptophan-ketoglutarate solution (HTK, Custodiol). HLEC cultures were preserved at 4 degrees C in CS, UW, and HTK, for 2, 6, 12, 24, and 48 hours, with 6 hours of reperfusion. Levels of lactate dehydrogenase (LDH), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and adenosine 5'-triphosphate (ATP) were measured after each interval of ischemia and the respective phase of reperfusion. Preservation injury of HLEC as measured by LDH release, intracellular ATP level, and MTT reduction were overall significantly (P <or= .01, P <or= .01, P < .05, respectively) lower in UW than in CS and HTK. CS demonstrates a modest superiority to HTK in HLEC preservation. Furthermore, cold preservation remains the main cause of preservation injury of HLEC regardless of the preservation solution used. Additionally, the maintenance of a high intracellular ATP level of HLEC after ischemia and reperfusion, as shown by UW, could be taken as a beneficial effect, particularly in long-term ischemia. In conclusion, our cell culture model reveals the order of efficacy to protect HLEC against preservation injury as: UW >> CS > HTK.


Insights into how phosphorylation of estrogen receptor at serine 305 modulates tamoxifen activity in breast cancer.
Estrogen receptor (ER) is the most important factor in the pathophysiology of breast cancer. Consequently, modulation of ER activity has been exploited to develop drugs against ER + breast cancer, such as tamoxifen, referred to as endocrine therapies. With deeper understanding of ER mechanism of action, posttranslational modifications (PTMs) are increasingly recognized as important in mediating ER activity. Some ER PTMs such as phosphorylation, are studied in the context of ligand-independent ER activity. However, they also play a pivotal role in defining the actions and outcome of the antiestrogen-bound ER. The complexity of these actions is increasing as new PTMs are identified, yet the functional consequences and clinical implications are not fully understood. This review will examine and summarize new emerging mechanistic knowledge and clinical data in breast cancer on how these PTMs affect antiestrogen-ER activity, with an emphasis on phosphorylation of serine 305 (S305). This phosphorylation site represents an integrated hub of oncogenic signaling to modulate ER conformation, dimerization, coregulators, and DNA binding to profoundly reduce sensitivity to endocrine therapy. Consequently, (i) S305 has the potential to become a useful marker of tamoxifen response, and (ii) blocking S305 phosphorylation defines a new therapeutic strategy to overcome tamoxifen resistance in breast cancer.


Atypical pathogens causing community-acquired pneumonia in adults.
To determine the frequency of community-acquired respiratory pathogens with special focus on atypical organisms in patients presenting to a tertiary care facility with community-acquired pneumonia (CAP). The descriptive study on adult patients was conducted from February 2007 to March 2008 at the Aga Khan University Hospital, Karachi. It comprised 124 consenting patients of age 16 and above who presentd with a diagnosis of community-acquired pneumonia. The diagnostic modalities used were based on significant changes in antibody titer or persisting high antibody titers in the case of Mycoplasma pneumoniae and Chalmydia pneumoniae infections, or bacterial antigen in urine, in the case of Legionella pneumophila serogroup 1 infection. Pyogenic bacteria were identified on the results of respiratory secretions or blood cultures. Continuous data and categorical variables were worked out using SPSS version 15. Among the 124 patients enrolled, an etiologic agent was identified in 44 (35.4%) patients. The most common organism was Mycoplasma pneumoniae (n = 21, 17%), followed by Chlamydia pneumoniae (n = 15, 12%), Streptococcus pneumoniae (n = 9, 7%), Haemophilus influenzae (n = 2, 1.6%), Klebsiella pneumoniae (n = 2, 1.6%) and Staphylococcus aureus (n = 1, 0.8%). Streptococcus pneumoniae was the most common organism isolated from blood cultures. No cases of Legionella pneumophila serogroup 1 were identified. Mycoplasma pneumoniae and Chalmydia pneumoniae are significant etiologic agents for community-acquired pneumonia occurring in Karachi. Local treatment guidelines for community-acquired pneumonia should include therapy directed specifically at these agents.


Recent advances on biodegradable polymeric carrier-based mucosal immunization: an overview.
Mucosal administration of vaccine is most prevalent way to induce desired immunity against various types of antigen and microbial in central and in addition, the peripheral blood in most external mucosal surface. Mucosal delivery of vaccine provides both humoral and cellular responses against mucosal infection. Mucosa, which are exposed to heavy loads of commensal and pathogenic microorganism, are one of the main region where infections are built up, also, thus have frontline status in immunity, making mucosa perfect site for vaccines application. The nasal route is favoured over parenteral route due to ease of administration, protection of antigen from degradation and induces sIgA which is not produced by systemic immunity. Natural and synthetic polymers are utilized to get nanoparticles carrier systems for development of nasal mucosal antibodies. The present review summarized the recent development in the field of vaccine delivery by means of mucoadhesive polymeric carriers. This review also describes the recent patent conceded for mucosal immunization utilizing these polymeric carriers.


Vibrio-bivalve interactions in health and disease.
In the marine environment, bivalve mollusks constitute habitats for bacteria of the Vibrionaceae family. Vibrios belong to the microbiota of healthy oysters and mussels, which have the ability to concentrate bacteria in their tissues and body fluids, including the hemolymph. Remarkably, these important aquaculture species respond differently to infectious diseases. While oysters are the subject of recurrent mass mortalities at different life stages, mussels appear rather resistant to infections. Thus, Vibrio species are associated with the main diseases affecting the worldwide oyster production. Here, we review the current knowledge on Vibrio-bivalve interaction in oysters (Crassostrea sp.) and mussels (Mytilus sp.). We discuss the transient versus stable associations of vibrios with their bivalve hosts as well as technical issues limiting the monitoring of these bacteria in bivalve health and disease. Based on the current knowledge of oyster/mussel immunity and their interactions with Vibrio species pathogenic for oyster, we discuss how differences in immune effectors could contribute to the higher resistance of mussels to infections. Finally, we review the multiple strategies evolved by pathogenic vibrios to circumvent the potent immune defences of bivalves and how key virulence mechanisms could have been positively or negatively selected in the marine environment through interactions with predators.


Association between restoration of autonomic modulation in the native sinus node and hemodynamic improvement after cardiac transplantation.
Little is known about the autonomic control of the native sinus node (NSN) after heart transplantation because its electrical activity is difficult to detect with skin electrodes. The intracardiac electrogram of the NSN and the donor heart electrocardiogram were measured simultaneously. A total of 351 recordings of 107 heart transplant patients (age 53.6+/-12.3 years) were obtained up to 1 year after transplantation. In a subgroup of 41 patients, consecutive recordings were made. Eleven recordings of heart failure patients (age 56.2+/-6.5 years) awaiting cardiac transplantation were used as controls. To examine a relationship between autonomic indices of the NSN and hemodynamics of the donor heart, intracardiac pressures and cardiac output were recorded in the same session. Heart rate variability (HRV) parameters in time and frequency domain of the NSN showed a significant increase starting at 6 months after transplantation, whereas heart rate of the NSN tended to decrease. Heart rate and HRV parameters remained constant over the first year in the donor heart. Higher values of low-frequency and high-frequency powers in the NSN were associated with lower values of right ventricular, pulmonary artery, and mean atrial pressure and cardiac output. Recordings of patients with rejection could not be distinguished from those without rejection based on the spectral content of HRV of either the NSN or the donor heart. These data suggest a restoration of autonomic modulation of the NSN. This restoration is associated with hemodynamic improvement of the donor heart.


Craniofacial operations and specialised centres: should they have a monopoly?
Contrary to several recent statements craniofacial operations should not be the monopoly of large specialised centres but may be handled successfully by well trained surgeons working in a good medical environment. The experience of the Geneva University Hospital is reviewed in this paper; there has been no death or major complication and the cosmetic results compare favourably with other series.


Recurrent and acquired tracheoesophageal fistulae (TEF)-Minimally invasive management.
Recurrent and acquired fistulae are a serious complication of congenital esophageal atresia and tracheoesophageal fistula (TEF) repair and foreign body ingestion (FBI) (e.g., button battery). We report our experience with a minimally invasive approach to recurrent and acquired TEF. Medical records of patients referred for management of recurrent and acquired TEF between 2003 and 2015 were reviewed retrospectively. Patients underwent endoscopic procedures (de-epithelization of fistulous tract and fibrin tissue adhesive-TisseelR) under general anesthesia. Nine children (7 male, 2 female) with age range 3months to 3years (mean 1.5year) were managed. TEF closed spontaneously in four patients, whereas in 5 patients the TEF closed after combined endoscopic procedure. Three patients required repeat endoscopic procedures. Follow-up ranged between 7months to 10years (mean 4.2years). Active observation and repeat combined endoscopic procedures are safe alternatives to open surgical repair of acquired and recurrent TEF. Level IV study.


Is higher compliance to brace therapy associated with poorer quality of life and self-image? A 36-months follow-up study.
Brace treatment is the most effective tool for avoiding curve progression in moderate adolescent idiopathic scoliosis and high adherence is required to achieve therapeutic success. Despite this, the compliance often is impaired by the concern about the psychological well-being of adolescents. This 36-month follow-up study investigated if the patients most adherent to brace treatment could report a stronger impairment in the quality of life and body image. 64 adolescents with idiopathic scoliosis responded to the Scoliosis Research Society-22 revised Patient Questionnaire at 12, 24, and 36 months after prescription of a TLSO rigid brace. Retrospectively, participants who wore a brace for more than 75% of the prescribed time were assigned to the good-compliance group (GC); the others formed the poor-compliance group (PC). At 12 months the GC group showed higher scores in treatment satisfaction and at 36 months they did not differ from the PC group in the overall SRS-22r score. Moreover, they achieved a statistically significant improvement in the scoliosis severity, although they showed lower scores in the self-image domain. In our patient's cohort, increased brace adherence does not compromise QoL and provides better treatment outcomes. However, more attention is needed to maintain good self-perception.


Distribution of scatter radiation by C-arm cone-beam computed tomography in angiographic suite: measurement of doses and effectiveness of protection devices.
Distribution of radiation by C-arm cone-beam computed tomography (CBCT) in the angiographic suite and effectiveness of protection devices were assessed. CBCT image of a human phantom was obtained by a rotation of 220 degrees during 8 seconds of exposure. One hundred and twelve dosimeters were placed at different positions around the beam entry site, and color maps of dose distributions were drawn for horizontal and vertical planes. The measurements showed the highest radiation dose over 600 μGy by a single CBCT image acquisition at a distance of 60 cm from the beam entry site and a height of 90 cm from the floor. The color maps demonstrated the dose distribution to be more intense at the bilateral directions of the phantom. With the use of a ceiling-mounted transparent lead-acryl screen and a table-suspended lead curtain, the doses were reduced by 45-92 % at a direction of 210 degrees and a distance of 120 cm.


Golgi-58K can re-localize to late endosomes upon cellular uptake of PS-ASOs and facilitates endosomal release of ASOs.
Phosphorothioate (PS) modified antisense oligonucleotide (ASO) drugs can trigger RNase H1 cleavage of cellular target RNAs to modulate gene expression. Internalized PS-ASOs must be released from membraned endosomal organelles, a rate limiting step that is not well understood. Recently we found that M6PR transport between Golgi and late endosomes facilitates productive release of PS-ASOs, raising the possibility that Golgi-mediated transport may play important roles in PS-ASO activity. Here we further evaluated the involvement of Golgi in PS-ASO activity by examining additional Golgi proteins. Reduction of certain Golgi proteins, including Golgi-58K, GCC1 and TGN46, decreased PS-ASO activity, without substantial effects on Golgi integrity. Upon PS-ASO cellular uptake, Golgi-58K was recruited to late endosomes where it colocalized with PS-ASOs. Reduction of Golgi-58K caused slower PS-ASO release from late endosomes, decreased GCC2 late endosome relocalization, and led to slower retrograde transport of M6PR from late endosomes to trans-Golgi. Late endosome relocalization of Golgi-58K requires Hsc70, and is most likely mediated by PS-ASO-protein interactions. Together, these results suggest a novel function of Golgi-58K in mediating Golgi-endosome transport and indicate that the Golgi apparatus plays an important role in endosomal release of PS-ASO, ensuring antisense activity.


Coevolution of tRNA intron motifs and tRNA endonuclease architecture in Archaea.
Members of the three kingdoms of life contain tRNA genes with introns. The introns in pre-tRNAs of Bacteria are self-splicing, whereas introns in archaeal and eukaryal pre-tRNAs are removed by splicing endonucleases. We have studied the structures of the endonucleases of Archaea and the architecture of the sites recognized in their pre-tRNA substrates. Three endonuclease structures are known in the Archaea: a homotetramer in some Euryarchaea, a homodimer in other Euryarchaea, and a heterotetramer in the Crenarchaeota. The homotetramer cleaves only the canonical bulge-helix-bulge structure in its substrates. Variants of the substrate structure, termed bulge-helix-loops, appear in the pre-tRNAs of the Crenarcheota and Nanoarcheota. These variant structures can be cleaved only by the homodimer or heterotetramer forms of the endonucleases. Thus, the structures of the endonucleases and their substrates appear to have evolved together.


Electrostatic contribution to twist rigidity of DNA.
The electrostatic contribution to the twist rigidity of DNA is studied, and it is shown that the Coulomb self-energy of the double-helical sugar-phosphate backbone makes a considerable contribution-the electrostatic twist rigidity of DNA is found to be C(elec) approximately 5 nm, which makes up about 7% of its total twist rigidity ( C(DNA) approximately 75 nm). The electrostatic twist rigidity is found, however, to depend only weakly on the salt concentration, because of a competition between two different screening mechanisms: (1) Debye screening by the salt ions in the bulk, and (2) structural screening by the periodic charge distribution along the backbone of the helical polyelectrolyte. It is found that, depending on the parameters, the electrostatic contribution to the twist rigidity could stabilize or destabilize the structure of a helical polyelectrolyte.


Additional properties of cetirizine, a new H1 antagonist.
Cetirizine, an H1 antihistamine, has properties in addition to H1 blockade that may be useful in the treatment of seasonal rhinitis and urticaria. For example, cetirizine has been shown to block the influx of eosinophils into the site of antigen-stimulated skin blisters. Studies with other antihistamines suggest that this is not a universal property of this type of drug. Pretreatment with cetirizine also has been found to block the augmented sensitivity to methacholine that occurs 24 hours after antigen provocation of the nasal mucosa. This reduction takes place despite the absence of an effect on eosinophil influx into this area, and suggests another action of cetirizine. Our study of allergic rhinitis patients examined the effect of cetirizine on early response to nasal challenge with antigen. Cetirizine, although it did not block the release into nasal secretions of histamine, significantly reduced sneezing and decreased levels of albumin and TAME-esterase activity, which are indicators of vascular permeability. Cetirizine also blocked the generation of leukotriene C4. In vitro studies have shown that cetirizine does not block the release of leukotriene from anti-IgE stimulated mast cells, raising the possibility that cells in the nasal mucosa in addition to mast cells generate leukotrienes.


Apoprotein E phenotype determines serum cholesterol in infants during both high-cholesterol breast feeding and low-cholesterol formula feeding.
Our objective was to establish the role of the apoprotein (apo) E phenotype in determining serum cholesterol levels in infants fed exclusively on high-fat, high-cholesterol human milk and in those fed a low-cholesterol, high-unsaturated fat formula. The total and lipoprotein cholesterol, apoB, and triglyceride concentrations in serum were quantified and related to the apoE phenotype in 151 infants at birth and at 2, 6, 9, and 12 months of age. Forty-four had the E3/4 or 4/4 phenotype (E4 group), 94 had the E3/3 phenotype (E3 group), and 13 had the E2/3 or 2/4 phenotype (E2 group). In cord blood, cholesterol concentrations tended to be higher in the E4 than in the E2 group. With exclusive breast-feeding, the concentrations rose significantly faster and higher in the E4 group than in the E3 group or, especially, the E2 group. The values (mmol/L, mean +/- SEM) were 1.6 +/- 0.15, 1.5 +/- 0.05, 1.4 +/- 0.1 (P = n.s.) at birth; 4.2 +/- 0.1, 3.8 +/- 0.08, 3.4 +/- 0.2 (P < 0.001) at 2 months; 4.4 +/- 0.15, 3.9 +/- 0.1, 3.4 +/- 0.15 (P < 0.001) at 4 months; 4.3 +/- 0.17, 4.0 +/- 0.13, 3.7 +/- 0.26 (P < 0.001) at 6 months; 4.8 +/- 0.28, 4.4 +/- 0.11, 3.8 +/- 0.05 (P < 0.001) at 9 months; and 4.7 +/- 0.11, 4.4 +/- 0.08, 4.1 +/- 0.19 (P < 0.001) at 12 months, for the E4, E3, and E2 groups, respectively. Increases in LDL cholesterol and LDL apoB behaved similarly. The total triglyceride, and total HDL, HDL2, and HDL3 cholesterol concentrations did not depend on the apoE phenotype. Among infants fed high-fat, high-cholesterol human milk, the total and LDL-cholesterol concentrations and the LDL apoB concentration of those with the apoE phenotype 4/4 or 3/4 rose faster and to higher levels than in other infants. Among formula-fed infants, receiving a low-cholesterol, high-unsaturated fat diet, the differences between the apoE groups were smaller.


Identification of novel candidate target genes in amplicons of Glioblastoma multiforme tumors detected by expression and CGH microarray profiling.
Conventional cytogenetic and comparative genomic hybridization (CGH) studies in brain malignancies have shown that glioblastoma multiforme (GBM) is characterized by complex structural and numerical alterations. However, the limited resolution of these techniques has precluded the precise identification of detailed specific gene copy number alterations. We performed a genome-wide survey of gene copy number changes in 20 primary GBMs by CGH on cDNA microarrays. A novel amplicon at 4p15, and previously uncharacterized amplicons at 13q32-34 and 1q32 were detected and are analyzed here. These amplicons contained amplified genes not previously reported. Other amplified regions containing well-known oncogenes in GBMs were also detected at 7p12 (EGFR), 7q21 (CDK6), 4q12 (PDGFRA), and 12q13-15 (MDM2 and CDK4). In order to identify the putative target genes of the amplifications, and to determine the changes in gene expression levels associated with copy number change events, we carried out parallel gene expression profiling analyses using the same cDNA microarrays. We detected overexpression of the novel amplified genes SLA/LP and STIM2 (4p15), and TNFSF13B and COL4A2 (13q32-34). Some of the candidate target genes of amplification (EGFR, CDK6, MDM2, CDK4, and TNFSF13B) were tested in an independent set of 111 primary GBMs by using FISH and immunohistological assays. The novel candidate 13q-amplification target TNFSF13B was amplified in 8% of the tumors, and showed protein expression in 20% of the GBMs. This high-resolution analysis allowed us to propose novel candidate target genes such as STIM2 at 4p15, and TNFSF13B or COL4A2 at 13q32-34 that could potentially contribute to the pathogenesis of these tumors and which would require futher investigations. We showed that overexpression of the amplified genes could be attributable to gene dosage and speculate that deregulation of those genes could be important in the development and progression of GBM. Our findings highlight the important influence in GBM of signaling pathways such as the PI3K/AKT, consistent with the invasive features of this tumor.


High functioning fragile X males: demonstration of an unmethylated fully expanded FMR-1 mutation associated with protein expression.
Fragile X (fra(X)) males with a standardized IQ score of 70 or higher represent a high functioning (HF) or nonretarded fra(X) male group. This group, which does not include nonpenetrant males, has received little research attention to date. Of 221 fra(X) males who had been evaluated through The Children's Hospital in Denver since 1981 and had completed cognitive or developmental testing, 29 (13%) were high functioning by the above definition. We found that HF males on the whole had a lower cytogenetic score and were younger than retarded fra(X) males, but there was no difference between these two groups in the number of typical fra(X) physical manifestations present. FMR-1 DNA testing was performed on 134 fra(X) males and methylation status was determined for 51 of these. A greater percentage of HF males had a mosaic pattern or an incompletely methylated full mutation than did retarded males. A unique DNA pattern, an unmethylated fully expanded mutation, was discovered in 3 of the highest functioning fra(X) males. Protein studies performed on 2 of these males demonstrated the presence of FMR-1 protein, albeit at lower levels than normal. FMR-1 protein was not present in retarded fra(X) males. Significant FMR-1 protein expression may be responsible for higher cognitive functioning in the 2 males with unmethylated fully expanded mutations compared to retarded fra(X) males.


Growth of highly oriented ZnO nanowires on GaN substrates for electronic and optical sensor applications.
In this Paper we present growth and characterization results of highly oriented ZnO nanowires grown on wide bandgap GaN substrates. Experimental results on the ZnO nanowires grown on p-GaN are presented with growth morphology and dimensionality control. We also present experimental results on these nanowire arrays such as I-V measurements and UV sensitivity measurements. The ZnO nanowires can be used for a variety of nanoscale optical and electronics applications.


[A new method for quantitative measurement of the cadmium absorbed by chick embryos].
We attempted to determine the quantity of cadmium incorporated in hens eggs after immersion in cadmium solutions, and the cadmium concentration measured in embryos. We discussed equipment allowing simultaneous treatment of up to 42 samples, and called it " digestor ". It consisted of two gas-heated sand baths, two stands for cooling down solutions and an evacuation system for toxic vapours. Our method was based on wet mineralisation. It consisted of desintegrating experimental chick embryos in a HNO3/H2O2 mixed solution. After heating and evaporating, the quantity of cadmium in the remnant was determined by atomic absorption spectrophotometry. The reliability of such a technique was tested by studying as controls controls 17 days-old chick embryos injected with a known quantity of Cd(NO3). It showed no loss of cadmium. We also compared our procedure with a dry ashing method. The latter showed unacceptable losses and insufficient precision for the problems we wanted to investigate. Our method gave us much more precise results. The equipment we developed has functioned wholly satisfactorily and allowed us to investigate for instance cadmium distribution and concentration in embryonic organs of 17 days-old chicks. It could also be useful for researches concerning other biological samples analyzed for different heavy metals.


ICI 118,551: an effective ocular hypotensive agent with selectivity for the ciliary process beta 2-adrenoceptor and with minimal cardiac side effects.
Prior biochemical studies have shown that the ciliary process epithelium, which is involved in the secretion of aqueous humour, is rich in beta-adrenoceptors with pharmacological characteristics similar to those of the beta 2 subclass. The present experiments demonstrate that the beta-adrenoceptor antagonist, ICI 118,551, is a potent inhibitor of isoprenaline-stimulated adenylate cyclase activity measured in broken cell preparations of rabbit ciliary process. In rabbit cardiac muscle, however, ICI 118,551 is a relatively weak antagonist of isoprenaline-stimulated adenylate cyclase, being approximately 100 fold less potent than the non-selective beta-adrenoceptor antagonist, timolol. ICI 118,551 is also less potent than timolol in inhibiting isoprenaline-sensitive adenylate cyclase of rabbit lung. ICI 118,551 applied topically to eyes of unanaesthetized rabbits causes a dose-dependent decrease in intraocular pressure. Furthermore, in a blind crossover study in rabbits, topically applied ICI 118,551 decreased intraocular pressure for more than 6 h and was more effective than an identical dose of the clinically effective anti-glaucoma agent, timolol. Systemic absorption from topically-applied timolol, but not ICI 118,551, is sufficient to alter cardiac response to subcutaneous administration of isoprenaline. Furthermore, dose-response studies, using direct systemic administration of the two beta-adrenoceptor antagonists, revealed that ICI 118,551 is about 60 times less potent than timolol in blocking isoprenaline-induced cardio-acceleration. ICI 118,551, applied to one eye, causes a decrease in intraocular pressure in the contralateral eye, and systemic administration of ICI 118,551 results in decreased intraocular pressure in both eyes, data indicating that at least part of the ocular hypotensive effect of topical ICI 118,551 is mediated through systemic absorption. 8 These findings provide biochemical and physiological evidence that selective beta 2-adrenoceptor blockers such as ICI 118,551, used topically or systemically, may be useful as ocular hypotensive agents with decreased cardiac side-effects.


Mechanochemical Decomposition of Crystalline Cellulose in the Presence of Protonated Layered Niobium Molybdate Solid Acid Catalyst.
Direct depolymerization of crystalline cellulose into water-soluble sugars by solvent-free ball milling was examined in the presence of a strongly acidic layered metal oxide, HNbMoO6 , resulting in full conversion with 72 % yield of water-soluble sugars. Measurements by 13 C cross-polarization magic angle spinning NMR spectroscopy and X-ray diffraction revealed that amorphization of cellulose occurred rapidly within 10 min. Scanning electron microscopy equipped with an energy dispersive X-ray indicated that the substrate and the catalyst were well mixed during milling. The time course of the product distribution showed that most of the resultant water-soluble sugars were produced not by successive degradation of oligosaccharides but by direct depolymerization of cellulose chains. The products included glucose, mannose, and cello-oligomers, as well as anhydrosugars. Addition of small amounts of polar solvents increased the sugar yield, whereas further addition of water decreased the selectivity to anhydrosugars. Calculations of the mechanical energy required for the ball-milling process showed that 0.02 % was utilized for the chemical transformation under the conditions examined in this study.


Influence of language experience on digit recognition by English and Chinese listeners.
Digit recognition was measured in quiet and in two noise conditions by English-native (EN) and Chinese-native (CN) listeners. EN listeners were tested using English digits and CN listeners were tested using both English and Chinese digits. In quiet, forward digit span recall worsened for both groups as the number of digits was increased. Significant effects of language experience were observed with five or more digits. Language experience had a significant effect on digit recognition in babble but not in steady noise. These results suggest that understanding of a nonnative language can be influenced by both cognitive load and listening environment.


Diagnostic value of liquid biopsy in the era of precision medicine: 10 years of clinical evidence in cancer.
Liquid biopsy is a diagnostic repeatable test, which in last years has emerged as a powerful tool for profiling cancer genomes in real-time with minimal invasiveness and tailoring oncological decision-making. It analyzes different blood-circulating biomarkers and circulating tumor DNA (ctDNA) is the preferred one. Nevertheless, tissue biopsy remains the gold standard for molecular evaluation of solid tumors whereas liquid biopsy is a complementary tool in many different clinical settings, such as treatment selection, monitoring treatment response, cancer clonal evolution, prognostic evaluation, as well as the detection of early disease and minimal residual disease (MRD). A wide number of technologies have been developed with the aim of increasing their sensitivity and specificity with acceptable costs. Moreover, several preclinical and clinical studies have been conducted to better understand liquid biopsy clinical utility. Anyway, several issues are still a limitation of its use such as false positive and negative results, results interpretation, and standardization of the panel tests. Although there has been rapid development of the research in these fields and recent advances in the clinical setting, many clinical trials and studies are still needed to make liquid biopsy an instrument of clinical routine. This review provides an overview of the current and future clinical applications and opening questions of liquid biopsy in different oncological settings, with particular attention to ctDNA liquid biopsy.


Intracranial hypertension: was it really idiopathic?
A healthy 44-year-old slim female presented with a constant, non-specific dull headache of subacute onset. The examination showed papilloedema but no other problem. On further questioning she revealed transient visual obscurations and pulsatile tinnitus. The CT scan of the brain was normal, the lumbar puncture showed increased pressure but normal cerebrospinal fluid, and the MR scan and MR venogram was reported showing a small area of developmental venous anomaly in the left parietal region but no venous thrombosis. Benign intracranial hypertension (BIH) was diagnosed but later in the course further tests were done as the patient was atypical for BIH, which revealed essential thrombocythaemia. A CT venogram was arranged which showed partly recanalised chronic sigmoid sinus thrombosis with dilation of collaterals. The patient was treated with acetazolamide, wafarin and hydroxycarbamide. The headache resolved quickly and the papilloedema reduced significantly over 6 months.


[Truth at bedside in relation to poor prognosis. Psychological aspects].
Patients as well as their physicians react in different ways to being confronted with imminent death. The physician has to decide which information to give a patient in which situation. A fatal prognosis has to be accompanied by clear and understandable information on chances and limits which are still important for the patient. This should also be the first step toward helpful and supporting guidance in the last period of life.


miR-152 controls migration and invasive potential by targeting TGFα in prostate cancer cell lines.
MicroRNAs (miRNAs) are a class of short non-coding RNAs that function in diverse biological processes. Aberrant miR-152 expression has been frequently reported in various malignant tumors. However, the mechanism of miR-152 in prostate cancer (PCa) remains unclear. This study aims to determine the function of miR-152 in PCa cells and identify the novel molecular targets regulated by miR-152. The expression levels of transforming growth factor-alpha (TGFα) were determined in three samples of PCa and adjacent non-tumorous tissues by Western blot analysis. miR-152 levels in 48 primary PCa and 15 non-malignant tissue samples were measured by qRT-PCR. The effects of forced miR-152 expression or TGFα knockdown on PCa cells were evaluated by cell migration and invasion assays, as well as Western blot analysis. Dual-luciferase reporter assay was used to identify binding sites between miR-152 and TGFα 3'-UTR. TGFα was upregulated in PCa tissue samples compared with that in adjacent normal ones. miR-152 expression was significantly decreased in primary PCa samples compared with that in non-malignant samples. Patients with Gleason scores >7 exhibited lower miR-152 levels than those with lower scores. Moreover, low miR-152 expression is correlated with advanced pathological T-stages. Forced miR-152 expression or TGFα knockdown significantly reduced the migratory and invasive capabilities of PCa cells in vitro. TGFα is a direct target gene of miR-152. Our findings suggest that miR-152 can act as a tumor suppressor that targets TGFα. miR-152 is a promising molecular target that inhibits PCa cell migration and invasion.


A Comparative Study of Basic, Amphoteric, and Acidic Catalysts in the Oxidative Coupling of Methanol and Ethanol for Acrolein Production.
The impact of acid/base properties (determined by adsorption microcalorimetry) of various catalysts on the cross-aldolization of acetaldehyde and formaldehyde leading to acrolein was methodically studied in oxidizing conditions starting from a mixture of methanol and ethanol. The aldol condensation and further dehydration to acrolein were carried out on catalysts presenting various acid/base properties (MgO, Mg-Al oxides, Mg/SiO2 , NbP, and heteropolyanions on silica, HPA/SiO2 ). Thermodynamic calculations revealed that cross-aldolization is always favored compared with self-aldolization of acetaldehyde, which leads to crotonaldehyde formation. The presence of strong basic sites is shown to be necessary, but a too high amount drastically increases COx production. On strong acid sites, production of acrolein and carbon oxides (COx ) does not increase with temperature. The optimal catalyst for this process should be amphoteric with a balanced acid/base cooperation of medium strength sites and a small amount (<100 μmol g-1 ) of very strong basic sites (Qdiff >150 kJ mol-1 ).


Closed compression technique for rupturing a contracted capsule around a breast implant.
When a breast becomes hard after an augmentation mammaplasty, the fibrous capsule around the implant can be ruptured, in most cases, by closed compression of the breast-resulting in immediate softness of the breast. As yet the duration of this improvement is unknown, but follow-up examinations to date indicate that it is persisting in about 3 or 4 patients so treated.


Multiple blocks of intermittent and continuous theta-burst stimulation applied via transcranial magnetic stimulation differently affect sensory responses in rat barrel cortex.
Theta-burst stimulation (TBS) applied via transcranial magnetic stimulation is able to modulate human cortical excitability. Here we investigated in a rat model how two different forms of TBS, intermittent (iTBS) and continuous (cTBS), affect sensory responses in rat barrel cortex. We found that iTBS but less cTBS promoted late (>18 ms) sensory response components while not affecting the earliest response (8-18 ms). The effect increased with each of the five iTBS blocks applied. cTBS somewhat reduced the early response component after the first block but had a similar effect as iTBS after four to five blocks. We conclude that iTBS primarly modulates the activity of (inhibitory) cortical interneurons while cTBS may first reduce general neuronal excitability with a single block but reverse to iTBS-like effects with application of several blocks. Cortical sensory processing varies with cortical state and the balance of inhibition to excitation. Repetitive transcranial magnetic stimulation (rTMS) has been shown to modulate human cortical excitability. In a rat model, we recently showed that intermittent theta-burst stimulation (iTBS) applied to the corpus callosum, to activate primarily supragranular cortical pyramidal cells but fewer subcortical neurons, strongly reduced the cortical expression of parvalbumin (PV), indicating reduced activity of fast-spiking interneurons. Here, we used the well-studied rodent barrel cortex system to test how iTBS and continuous TBS (cTBS) modulate sensory responses evoked by either single or double stimuli applied to the principal (PW) and/or adjacent whisker (AW) in urethane-anaesthetized rats. Compared to sham stimulation, iTBS but not cTBS particularly enhanced late (>18 ms) response components of multi-unit spiking and local field potential responses in layer 4 but not the very early response (<18 ms). Similarly, only iTBS diminished the suppression of the second response evoked by paired PW or AW-PW stimulation at 20 ms intervals. The effects increased with each of the five iTBS blocks applied. With cTBS a mild effect similar to that of iTBS was first evident after 4-5 stimulation blocks. Enhanced cortical c-Fos and zif268 expression but reduced PV and GAD67 expression was found only after iTBS, indicating increased cortical activity due to lowered inhibition. We conclude that iTBS but less cTBS may primarily weaken a late recurrent-type cortical inhibition mediated via a subset of PV+ interneurons, enabling stronger late response components believed to contribute to the perception of sensory events.


Malignant gastric lymphoma with spontaneous perforation.
Malignant gastric lymphoma, accounting only for 1% of primary gastric carcinoma, is usually a diffuse large B-cell lymphoma. Toyota et al reported that 37% of gastric perforations involved malignancy, generally gastric carcinoma. Fukuda et al found that less than 5% of malignant gastric lymphomas perforate. While it is relatively well known that perforations often take place during chemotherapy, they are rare in patients not receiving chemotherapy. To our knowledge, spontaneous perforation is rare in gastric malignant lymphoma, having been reported in the Japanese literature only 26 times, including this case, in the last 25 years.


Mycoflora inhabiting water closet environments.
Sixty-six fungal species in addition to two species varieties belonging to 31 genera were isolated during the current study from water closet (WC) sewage samples (39 species and two varieties in 20 genera) and WC air (53 species and two varieties in 25 genera). There were more fungi in the WC air than in sewage. The most prevalent fungi in WC sewage and air were members of the genera Aspergillus, Cladosporium and Penicillium. Acremonium, Alternaria, Emericella, Mycosphaerella and Pleospora were dominant only in WC air. Some species of these genera are considered to be true or opportunistic pathogens. The pollution level due to the bacterial flora either in the air or in the sewage of WCs was relatively higher than that of the fungal flora. Testing the capability to produce urease, nearly all fungal isolates (65 out of 67) and bacteria tested (35 out of 36) proved to be good urease producers.


Recognition failure and integration.
If a recognition test is followed by a cued recall test then the probability of recognition given recall generally follows the Tulving-Wiseman function. Despite this regularity two types of exceptions have been discovered. Both poor integration and cue overlap causes an observed value of recognition given recall that is higher than predicted. The present study explores the first type of exception by proposing and testing an analytical tool, which emanates from confidence ratings given to recall responses, for relating poor integration directly to variations in the degree of deviation from the function. It is demonstrated that very poor integration produces a deviation above the function, whereas a very good integration produces a deviation below the function. The effect of integration (and cue overlap) is explained by means of a conceptualization cue dependency. Support is also given to the notion that an enhanced variability of goodness of encoding contributes to an enhanced dependence between recall and recognition.


The role of miR-101 in esophageal and gastric cancer.
miR-101 is downregulated in various types of cancer, leading to the notion that miR-101 acts as a suppressor in cancer cell progression. The comprehensive mechanisms underlying the effects of miR-101 and the exact role of miR-101 dysregulations in esophagogastric tumors have not been fully elucidated. This review aims to summarize all current knowledge on the association between miR-101 expression and esophagogastric malignancies and to clarify the pathogenetic pathways and the possible prognostic and therapeutic role of miR-101 in those cancer types. miR-101 seems to play crucial role in esophageal and gastric cancer biology and tumorigenesis. It could also be a promising novel diagnostic and therapeutic target, as well as it may serve as a significant predictive biomarker in esophagogastric cancer.


Organic and solution-processed tandem solar cells with 17.3% efficiency.
Although organic photovoltaic (OPV) cells have many advantages, their performance still lags far behind that of other photovoltaic platforms. A fundamental reason for their low performance is the low charge mobility of organic materials, leading to a limit on the active-layer thickness and efficient light absorption. In this work, guided by a semi-empirical model analysis and using the tandem cell strategy to overcome such issues, and taking advantage of the high diversity and easily tunable band structure of organic materials, a record and certified 17.29% power conversion efficiency for a two-terminal monolithic solution-processed tandem OPV is achieved.


Evaluation of knowledge and practice of hairdressers in men's beauty salons in Isfahan about hepatitis B, hepatitis C, and AIDS in 2010 and 2011.
Blood-borne viruses such as hepatitis B, hepatitis C, and human immunodeficiency virus (HIV) have infected millions of people worldwide. During haircut or shaving, barbers may accidentally expose to their clients' blood, transmit their own infection to them, or transmit the infection from one client to another. So the knowledge of barbers toward topics related to AIDS, hepatitis B, and C are of great importance. This cross-sectional descriptive study was performed in 2010-2011 in men's beauty salons in Isfahan town. A multistage sampling was performed. The knowledge assessment questionnaire and the checklist of practice regarding hepatitis B, C, and AIDS were completed by trained interviewers. In our study, 240 hairdressers participated. There was a statistically significant relationship between the education level and knowledge score of the hairdressers (P = 0.048). We found a statistically significant relationship between the knowledge level and the working history of hairdressers according to the Pearson's correlation coefficient (P = 0.02). The results show significant relationship between the education level and the practice scores (P = 0.005). Also the working history of hairdressers and their practice score had a significant relationship (P = 0.005). The results did not show significant relationship between the age of the hairdressers and the practice scores (P = 0.12). We obtained promising results about the knowledge and practice levels of the staff of men's beauty shop in Isfahan about AIDS, hepatitis B, and C. However, but because of the important role of barbers in virus transmission, we should provide the best program for control, evaluation, continuous teaching programs.


Use of Multimodal Long-Wave Infrared Thermography Devices in Clinical Practice.
The current practice of assessing wounds is highly dependent on visual examination and clinical judgment; these methods are highly subjective and leave great room for error. Objective measures of wound severity and healing are necessary tools that have been lacking in clinical practice. Long-wave infrared thermography (LWIT) has diverse applications that can be optimized to help detect and monitor wounds. This work is a retrospective case series of pertinent patients encountered by the authors in clinical practice. Nine cases were ultimately selected to best represent the multitude of benefits that can be seen with the utilization of LWIT devices. Through this case series, we show the many advantages of LWIT devices. This technology is safe, noninvasive, and user friendly and, most importantly, gives objective, instant, and repeatable measurements.


Surgical thrombectomy of two left ventricular thrombi in a child with acute myocarditis.
Myocarditis is a potentially life-threatening disease. Although ventricular thrombus formation in myocarditis is rare, it carries the risk of serious complications. We report on a 10-year-old previously healthy girl presenting with 2 large left ventricular thrombi in acute lymphocytic acute myocarditis. No coagulation disorder was found. Her clinical course and mobile thrombi characteristics prompted us to carry out an urgent surgical thrombectomy rather than primary anticoagulation therapy. The patient has recovered well without clinical signs of thromboembolism.


Dual energy CT for the identification of CSF-Venous Fistulas and CSF leaks in spontaneous intracranial hypotension: Report of four cases.
Spontaneous intracranial hypotension (SIH) is a debilitating condition caused by spinal CSF leaks or CSF-venous fistulas (CVFs). Localizing the causative CSF leak or CVF is critical for definitive treatment but can be difficult using conventional myelographic techniques because these lesions are often low contrast compared to background, diminutive, and in some cases may be mistaken for calcified structures. Dual energy CT (DECT) can increase the conspicuity of iodinated contrast compared to background and can provide the ability to distinguish materials based on differing anatomic properties, making it well suited to address the shortcomings of conventional myelography in SIH. The purpose of this report is to illustrate the potential benefits of using DECT as an adjunct to traditional myelographic techniques in order to increase the conspicuity of these often-subtle CVFs and CSF leaks. This retrospective case series included 4 adult patients with SIH who demonstrated findings equivocal for either CVF or CSF leak using our institution's standard initial CT myelogram and in whom subsequent evaluation with DECT ultimately helped to identify the CVF or CSF leak. DECT demonstrated utility by increasing the conspicuity of two subtle CVFs compared to background and also helped to differentiate between calcified osteophytes and extradural contrast in 2 CSF leaks, confirming their presence and identifying the causative pathology. Our observations demonstrate the benefit of DECT as a problem-solving tool in the accurate diagnosis and localization of CVFs and CSF leaks.


Identification and characterization of a novel conserved 46 kD maltoporin of Aeromonas hydrophila as a versatile vaccine candidate in European eel (Anguilla anguilla).
European eel (Anguilla anguilla) is a crucial economic fish that has been plagued by Aeromonas hydrophila infections for many years. Vaccines that are cross-protective against multiple serotypes could provide an effective control against A. hydrophila-mediated diseases. The outer membrane proteins (OMPs) are highly immunogenic and capable of eliciting protective immune responses. This study reports the identification of a novel 46 kD maltoporin that is a conserved protective antigen for different serotypes of A. hydrophila. First, this study purified OMPs from the strains of A. hydrophila B10, B11, B12, B15, B19, and B20. Western blot analysis revealed that the 46 kD maltoporin of B11 could be strongly reacted with all the specific European eel antisera against the above OMPs from different serotypes A. hydrophila. Cloning and sequencing of the maltoporin revealed that it contains an open reading frame (ORF) of 1281 nucleotides encoding 426 amino acids. Further sequence alignment analysis using the NCBI Conserved Domain Database (CDD) along with performing three-dimensional structure analysis showed that this protein belongs to maltoporin family. Three different study groups of European eels were intraperitoneal injected with one of the following conditions: phosphate-buffered saline (PBS group), formaline-killed-whole-cell (FKC) of A. hydrophila (FKC group) or with the recombinant maltoporin (OMP group) to analyze the immunogenicity of the recombinant maltoporin purified by nickel chelate affinity chromatography. On 14, 21, 28 and 42 days post-vaccination respectively, proliferation of the whole blood cells, titers of specific antibody, and lysozyme activities of experimental eels were detected. On 28d post-vaccination, eels from the three groups were challenged by intraperitoneal injection with five different live strains of A. hydrophila (B10, B11, B15, B19, and B20). The results showed that the proliferation of whole blood cells in the OMP group was significantly enhanced on 14d and the serum antibody titers of vaccinated European eels in FKC and OMP group were significantly increased on 28d and 42d. Lysozyme activities in serum were significantly up-regulated in FKC and OMP groups on 21d. The relative percent survival (RPS) of OMP group challenged by A. hydrophila B10, B11, and B20 was 75%, 62.5%, and 88%. This was higher than the corresponding RPS of FKC group with 50%, 37.5%, and 66%, respectively. The RPS was up to 100% in both OMP and FKC group when challenged by A. hydrophila B15 and B19. These results indicate that the 46 kD maltoporin is an effective potent vaccine candidate against different serotypes of A. hydrophila.


Can patients with obsessive-compulsive disorder discriminate between percepts and mental images? A signal detection analysis.
Signal detection analysis was used to test three hypotheses for repetitive thoughts and behaviors characteristic of obsessive-compulsive disorder (OCD). Patients might have (a) low sensitivity for the difference between having seen something or having imagined seeing it, (b) a high criterion for this discrimination, or (c) difficulty associating context with information in memory. Subjects judged viewed words or imagined words and later indicated which were actually seen. Patients with OCD discriminated seen from imaged words significantly better than normal control subjects, as evidenced by higher d' scores on a recognition memory task. Groups did not differ in response criterion, beta, used to decide whether words had been seen or imaged. Implications for the study of OCD from an information-processing perspective are discussed.


SEMAPHORE1 functions during the regulation of ancestrally duplicated knox genes and polar auxin transport in maize.
The expression of class 1 knotted1-like homeobox (knox) genes affects numerous plant developmental processes, including cell-fate acquisition, lateral organ initiation, and maintenance of shoot apical meristems. The SEMAPHORE1 gene product is required for the negative regulation of a subset of maize knox genes, the duplicated loci rough sheath 1 and gnarley1 (knox4). Recessive mutations in semaphore1 result in the ectopic expression of knox genes in leaf and endosperm tissue. Genetic analyses suggest that SEMAPHORE1 may regulate knox gene expression in a different developmental pathway than ROUGH SHEATH2, the first-identified regulator of knox gene expression in maize. Mutations at semaphore1 are pleiotropic, disrupting specific domains of the shoot. However, unlike previously described mutations that cause ectopic knox gene expression, semaphore1 mutations affect development of the embryo, endosperm, lateral roots, and pollen. Moreover, polar transport of the phytohormone auxin is significantly reduced in semaphore1 mutant shoots. The data suggest that many of the pleiotropic semaphore1 phenotypes result from defective polar auxin transport (PAT) in sem1 mutant shoots, and support models correlating down-regulated knox gene expression and PAT in maize shoots.


Unique Solid-State Emission Behavior of Aromatic Difluoroboronated β-Diketones as an Emitter in Organic Light-Emitting Devices.
Aromatic difluoroboronated β-diketone (BF2 DK) derivatives are a widely known class of luminescent organic materials that exhibit high photoluminescent quantum efficiency and unique aggregation-dependent fluorescence behavior. However, there have been only a few reports on their use in solid-state electronic devices, such as organic light-emitting devices (OLEDs). Herein, we investigated the solid-state properties and OLED performance of a series of π-extended BF2 DK derivatives that have previously been shown to exhibit intense fluorescence in the solution state. The BF2 DK derivatives formed exciplexes with a carbazole derivative and exhibited thermally activated delayed fluorescence (TADF) behavior to give orange electroluminescence with a peak external quantum efficiency of 10 % that apparently exceeds the theoretical efficiency limit of conventional fluorescent OLEDs (7.5 %), assuming a light out-coupling factor of 30 %.


Types of Male Adolescent Violence Against Women in Three Contexts: Dating Violence Offline, Dating Violence Online, and Sexual Harassment Online Outside a Relationship.
There has been little investigation of male adolescent violence against women as acknowledged by boys themselves, and even less on such violence in different contexts with comparative studies of behavior between those who perpetrate this violence and the population at large. This study used cluster analysis to establish a male adolescent typology based on boys' self-reporting of violence against women in three contexts. The participants were 3,132 Spanish teenage boys aged 14-18 with experience of relationships with girls. Three discrete, identifiable types were obtained: the first group (69.8%), of non-violent boys; the second group (26%), more involved in sexual harassment online outside a relationship but with a low incidence of dating violence offline; the third group (4.2%), with abuse in the three contexts but less involved in sexual harassment online than the second group. The logistic regression analysis showed that justification of male dominance and violence was the main risk condition for inclusion in the second and third groups, followed by low self-esteem (for the third group) and risky sexual behaviors online (for the second and third groups). The findings based on these results are important for preventing male adolescent dating violence against women in the three male types detected.


Optimizing Pain Control and Minimizing Opioid Use in Trauma Patients.
Adverse effects of opioids and the ongoing crisis of opioid abuse have prompted providers to reduce prescribing opioids and increase use of multiple nonpharmacologic therapies, nonopioid analgesics, and co-analgesics for pain management in trauma patients. Nonopioid agents, including acetaminophen, nonsteroidal anti-inflammatory drugs, gabapentinoids, ketamine, central α2 agonists, and lidocaine, can be used as adjuncts or alternatives to opioids in the trauma population. Complementary therapies such as acupuncture, virtual reality, and mirror therapy are modalities that also may be helpful in reducing pain. Performing pain assessments is fundamental to identify pain and evaluate treatment effectiveness in the critically ill trauma patient. The efficacy, safety, and availability of opioid-sparing therapies and multimodal pain regimens are reviewed.


[The beginnings of independent dental education at the Medical University of Budapest].
Independent dental education in Hungary has been started in September 1952 at the University of Budapest. The previous system based on a diploma in general medicine + a postgraduate-specialist education has been stopped, although the claim on dentists has grown significantly in the country. The Dental Section of the Medical-Health Trade Union with the aim to solve this problem, accepted the establishment of an independent dental faculty within the Medical University of Budapest. The educational reform became realised in 1952 by an official regulation. The new class started to study at the Clinic of Stomatology, taught by the staff of the clinic.


Effect of Outcome Measures on the Apparent Efficacy of Ablation for Atrial Fibrillation: Why "Success" is an Inappropriate Term.
Different endpoint criteria, different durations of follow-up and the completeness of follow-up can dramatically affect the perceived benefits of atrial fibrillation (AF) ablation. We defined three endpoints for recurrence of AF post ablation in a cohort of 200 patients with symptomatic AF, refractory to antiarrhythmic drugs (AADs). A 'Strict Endpoint' where patients were considered to have a recurrence with any symptomatic or documented recurrence for ≥30 seconds with no blanking period, and off their AADs, a 'Liberal Endpoint' where only documented recurrences after the blanking period, either on or off AADs were counted, and a 'Patient-defined Outcome endpoint' which was the same as the Liberal endpoint but allowed for up to two recurrences and one repeat ablation or DCCV during follow-up. We also surveyed 50 patients on the waiting list for an AF ablation and asked them key questions regarding what they would consider to be a successful result for them. Freedom from recurrence of atrial tachyarrhythmias (AT) at 5 years was 62% for the Strict Endpoint, 73% for the Liberal Endpoint, and 80% for the Patient-defined Outcome endpoint (p<0.001). Of the 50 patients surveyed awaiting AF ablation, 70% said they would still consider the procedure a success if it required one repeat ablation or one DCCV (p=0.004), and 76% would be accepting of one or two recurrences during follow-up (p<0.001). In this study, the majority of patients still considered AF ablation a successful treatment if they had up to two recurrences of AF, one repeat procedure or one DCCV. Furthermore, a 'Patient-defined' definition of success lead to significantly different results in this AF ablation cohort when compared to conventionally used/guideline directed measures of success.


[Electrophysiological appropriateness technique based on TCM meridian theory for postoperative pain after urethral reconstruction: A real-world study].
To investigate the clinical efficacy of electrophysiological appropriateness technique (EAT) therapy based on the traditional Chinese medicine (TCM) meridian theory in managing postoperative pain after urethral reconstruction surgery. Using the real-world study approach, we enrolled 61 male patients undergoing urethral reconstruction and divided them into a control group (n = 30) and an observation group (n = 31), the former receiving patient-controlled intravenous analgesia (PCIA), while the latter PCIA plus EAT at 4 pairs of acupoints (Hegu, Neiguan, Zusanli and Sanyinjiao bilaterally) and the Ashi point, with 100 mg tramadol hydrochloride given orally as remedial analgesia in both groups in case of postoperative Visual Analogue Scale (VAS) score ≥4. We compared the VAS scores at 4, 12, 24 and 48 hours postoperatively, the dose of cumulative fentanyl used at 48 hours, the number of cases needing remedial analgesia, the time to first flatus and the incidence of adverse reactions between the two groups of patients. The VAS scores were markedly lower in the observation than in the control group at 4, 12, 24 and 48 hours after surgery (P < 0.05), with statistically significant differences in time-dependent effect and interactive effect (P < 0.05). Significant reduction was observed in the doses of cumulative fentanyl (P < 0.05) and remedial tramadol analgesia (P < 0.05), time to first flatus (P < 0.05), and incidence of adverse reactions (P < 0.05) in the observation group in comparison with the controls. Electrophysiological therapy based on the TCM meridian theory can safely and effectively alleviate postoperative pain after urethral reconstruction, reduce opioid consumption, and decrease adverse events.


Antisolvent with an Ultrawide Processing Window for the One-Step Fabrication of Efficient and Large-Area Perovskite Solar Cells.
Photovoltaic technologies based on perovskite absorber materials have led this optoelectronic field into a brand-new horizon. However, the present antisolvents used in the one-step spin-coating method always encounter problems with the very narrow process window. Herein, anisole is introduced into the one-step spin-coating method, and the technology is developed to fabricate perovskite thin films with ultrawide processing window with a dimethylformamide (DMF):dimethyl sulfoxide (DMSO) ratio varying from 6:4 to 9:1 in the precursor solution, anisole dripping time ranging from 5 to 25 s, and an antisolvent volume varying from 0.1 to 0.9 mL. Perovskite thin films as large as 100 cm2 are successfully fabricated using this method. Maximum photoelectric conversion efficiencies of 19.76% for small-area (0.14 cm2 ) and 17.39% for large-area (1.08 cm2 ) perovskite solar cell devices are obtained. It is also found that there are intermolecular hydrogen-bonding forces between anisole and DMF/DMSO that play critical roles in the wide process window. These results provide a deeper understanding of the crystallizing procedure of perovskite during the one-step spin-coating process.


Structure-Function Relationship between Frequency-Doubling Technology Perimetry and Optical Coherence Tomography in Glaucoma.
Purpose: To assess the relationship between the retinal nerve fibre layer (RNFL) thickness and the frequency-doubling technology perimetry (FDT) outcome. Methods: Sixty-two healthy individuals and 72 glaucoma patients were prospectively selected. All participants underwent a reliable FDT and optical coherence tomography (OCT). Pearson correlations were calculated between the unlogged threshold values of FDT and RNFL thicknesses measured by OCT. Results: Mild to moderate correlations were found between a few points from FDT and RNFL thicknesses in the vertical axis. The nasal superior area of FDT and the RNFL thickness at the 7-o'clock position had the strongest correlation (0.434, p < 0.001). Conclusions: The poor agreement between FDT and OCT parameters suggests that both instruments assess different characteristics of glaucomatous optic neuropathy. The map obtained validates previously reported clinical findings and contributes to a better understanding of the structure-function relationship in glaucoma. © 2014 S. Karger AG, Basel.


Advanced data management for optimising the operation of a full-scale WWTP.
The lack of appropriate data management tools is presently a limiting factor for a broader implementation and a more efficient use of sensors and analysers, monitoring systems and process controllers in wastewater treatment plants (WWTPs). This paper presents a technical solution for advanced data management of a full-scale WWTP. The solution is based on an efficient and intelligent use of the plant data by a standard centralisation of the heterogeneous data acquired from different sources, effective data processing to extract adequate information, and a straightforward connection to other emerging tools focused on the operational optimisation of the plant such as advanced monitoring and control or dynamic simulators. A pilot study of the advanced data manager tool was designed and implemented in the Galindo-Bilbao WWTP. The results of the pilot study showed its potential for agile and intelligent plant data management by generating new enriched information combining data from different plant sources, facilitating the connection of operational support systems, and developing automatic plots and trends of simulated results and actual data for plant performance and diagnosis.


Isolation of Actinobacillus pleuropneumoniae serovar 15-like strain from a field case of porcine pleuropneumonia in Japan.
An Actinobacillus pleuropneumoniae strain isolated from a field case of porcine pleuropneumonia in Japan, was closely related to a reference strain of serovar 15, which is a newly proposed serovar according to an analysis of field isolates originating from Australia. The isolate had biological and biochemical properties consistent with A. pleuropneumoniae biovar 1, and reacted strongly to a rabbit antiserum raised against a reference strain of serovar 15 in an agar gel precipitation test. The nucleotide sequence of a hyper variable region in the 16S RNA gene of the isolate was identical to that of the reference strain of serovar 15. The isolate possessed A. pleuropneumoniae-RTX toxin (Apx) II, III, and IV genes, consistent with serovar 15. Its virulence in mice was lower than that of ApxI-bearing strains but higher than that of other ApxIII-bearing strains. This is the first report describing the isolation of A. pleuropneumoniae serovar 15-like strain from a country or region other than Australia.


Monocytes of patients with familial hypercholesterolemia show alterations in cholesterol metabolism.
Elevated plasma cholesterol promotes the formation of atherosclerotic lesions in which monocyte-derived lipid-laden macrophages are frequently found. To analyze, if circulating monocytes already show increased lipid content and differences in lipoprotein metabolism, we compared monocytes from patients with Familial Hypercholesterolemia (FH) with those from healthy individuals. Cholesterol and oxidized cholesterol metabolite serum levels of FH and of healthy, gender/age matched control subjects were measured by combined gas chromatography - mass spectroscopy. Monocytes from patients with FH and from healthy subjects were isolated by antibody-assisted density centrifugation. Gene expression profiles of isolated monocytes were measured using Affymetrix HG-U 133 Plus 2.0 microarrays. We compared monocyte gene expression profiles from FH patients with healthy controls using a Welch T-test with correction for multiple testing (p < 0.05; Benjamini Hochberg correction, False Discovery Rate = 0.05). The differential expression of FH associated genes was validated at the mRNA level by qRT-PCR and/or at the protein level by Western Blot or flow cytometry. Functional validation of monocyte scavenger receptor activities were done by binding assays and dose/time dependent uptake analysis using native and oxidized LDL. Using microarray analysis we found in FH patients a significant up-regulation of 1,617 genes and a down-regulation of 701 genes compared to monocytes from healthy individuals. These include genes of proteins that are involved in the uptake, biosynthesis, disposition, and cellular efflux of cholesterol. In addition, plasma from FH patients contains elevated amounts of sterols and oxysterols. An increased uptake of oxidized as well as of native LDL by FH monocytes combined with a down-regulation of NPC1 and ABCA1 explains the lipid accumulation observed in these cells. Our data demonstrate that circulating FH monocytes show differences in cell physiology that may contribute to the early onset of atherosclerosis in this disease.


Material-specific difficulties in episodic memory tasks in mild traumatic brain injury.
The study examines acute, material-specific secondary memory performance in 26 patients with mild traumatic brain injury (MTBI) and 26 healthy controls, matched on demographic variables and indexes of crystallized intelligence. Neuropsychological tests were used to evaluate primary and secondary memory, executive functions, and verbal fluency. Participants were also tested on episodic memory tasks involving words, pseudowords, pictures of common objects, and abstract kaleidoscopic images. Patients showed reduced performance on episodic memory measures, and on tasks associated with visuospatial processing and executive function (Trail Making Test part B, semantic fluency). Significant differences between groups were also noted for correct rejections and response bias on the kaleidoscope task. MTBI patients' reduced performance on memory tasks for complex, abstract stimuli can be attributed to a dysfunction in the strategic component of memory process.


Metastatic retinoblastoma successfully treated with immunomagnetic purged autologous bone marrow transplantation.
There are no documented cases of long-term, disease-free survival in retinoblastoma (RB) metastatic to the bone marrow. The following study details successful outcome in a 3-year-old child with extensive marrow replacement 7 months postenucleation in an otherwise untreated group V RB. Therapy consisted of combinations of vincristine, doxorubicin, and cyclophosphamide for 3 months. After demonstrating cross-reactivity by a panel of six monoclonal neuroblastoma (NB) antibodies with the patient's RB cells, her marrow was purged by using microsphere-linked monoclonal antibodies, and then reinfused as rescue therapy after ablative doses of etoposide and cyclophosphamide. The authors conclude that short-term induction therapy followed by marrow ablative combination chemotherapy and immunomagnetically purged autologous marrow rescue can (1) effect successful outcome in widely metastatic RB, and (2) eliminate the risk of therapy-induced second malignancies.


Synthesis, molecular modeling investigation, molecular dynamic and ADME prediction of some novel Mannich bases derived from 1,2,4-triazole, and assessment of their anticancer activity.
A series of biologically active novel Mannich bases containing with a 1H-1,2,4-triazole-5-one ring were developed to evaluate the cytotoxic activity. For this purpose, the synthesized Schiff Bases (S1-5) were reacted with formaldehyde and morpholine, which is a secondary amine to yield novel N-Mannich bases (M1-5) via the Mannich reaction. The structures of the compounds (M1-5) were determined structurally employing 1H/13C-NMR, IR and elemental analysis. In this study, we evaluated the cytotoxic potential of the compounds (M1-5) on the human hypopharyngeal carcinoma FaDu cells. We found that the compound (M3) possesses a significant anticancer feature against FaDu cells that might be evaluated with further in vitro and in vivo studies to understand its anticancer potential better. Lastly, comparisons were made using molecular docking calculations to find the theoretical activities of the compounds (M1-5). The docking score parameter of the compound (M3) against the 2DO4 protein is -5.67, the docking score parameter against the 5JPZ protein is -5.72, and finally, the docking score parameter against the 2H80 protein is -5.50. Molecular dynamic calculations are made for 0-100 ns. The ADME/T calculations were performed to find the drug potential of the compounds (M1-5). The results suggest that our drug candidate compound exhibits strong potential for co-administration with the antigen structures, owing to the low rate of interactions that decreased over time.Communicated by Ramaswamy H. Sarma.


Moderated statistical tests for assessing differences in tag abundance.
Digital gene expression (DGE) technologies measure gene expression by counting sequence tags. They are sensitive technologies for measuring gene expression on a genomic scale, without the need for prior knowledge of the genome sequence. As the cost of sequencing DNA decreases, the number of DGE datasets is expected to grow dramatically. Various tests of differential expression have been proposed for replicated DGE data using binomial, Poisson, negative binomial or pseudo-likelihood (PL) models for the counts, but none of the these are usable when the number of replicates is very small. We develop tests using the negative binomial distribution to model overdispersion relative to the Poisson, and use conditional weighted likelihood to moderate the level of overdispersion across genes. Not only is our strategy applicable even with the smallest number of libraries, but it also proves to be more powerful than previous strategies when more libraries are available. The methodology is equally applicable to other counting technologies, such as proteomic spectral counts. An R package can be accessed from http://bioinf.wehi.edu.au/resources/


TCF3 Regulates the Proliferation and Apoptosis of Human Spermatogonial Stem Cells by Targeting PODXL.
Spermatogonial stem cells (SSCs) are the initial cells for the spermatogenesis. Although much progress has been made on uncovering a number of modulators for the SSC fate decisions in rodents, the genes mediating human SSCs remain largely unclear. Here we report, for the first time, that TCF3, a member of the basic helix-loop-helix family of transcriptional modulator proteins, can stimulate proliferation and suppress the apoptosis of human SSCs through targeting podocalyxin-like protein (PODXL). TCF3 was expressed primarily in GFRA1-positive spermatogonia, and EGF (epidermal growth factor) elevated TCF3 expression level. Notably, TCF3 enhanced the growth and DNA synthesis of human SSCs, whereas it repressed the apoptosis of human SSCs. RNA sequencing and chromatin immunoprecipitation (ChIP) assays revealed that TCF3 protein regulated the transcription of several genes, including WNT2B, TGFB3, CCN4, MEGF6, and PODXL, while PODXL silencing compromised the stem cell activity of SSCs. Moreover, the level of TCF3 protein was remarkably lower in patients with spermatogenesis failure when compared to individuals with obstructive azoospermia with normal spermatogenesis. Collectively, these results implicate that TCF3 modulates human SSC proliferation and apoptosis through PODXL. This study is of great significance since it would provide a novel molecular mechanism underlying the fate determinations of human SSCs and it could offer new targets for gene therapy of male infertility.


A discussion about public health, lead and Legionella pneumophila in drinking water supplies in the United States.
Lead (Pb) in public drinking water supplies has garnered much attention since the outset of the Flint water crisis. Pb is a known hazard in multiple environmental matrices, exposure from which results in long-term deleterious health effects in humans. This discussion paper aims to provide a succinct account of environmental Pb exposures with a focus on water Pb levels (WLLs) in the United States. It is understood that there is a strong correlation between WLLs and blood Pb levels (BLLs), and the associated health effects. However, within the Flint water crisis, more than water chemistry and Pb exposure occurred. A cascade of regulatory and bureaucratic failures culminated in the Flint water crisis. This paper will discuss pertinent regulations and responses including their limitations after an overview of the public health effects from Pb exposure as well as discussion on our limitations on monitoring and mitigating Pb in tap water. As the Flint water crisis also included increased Legionnares' disease, caused by Legionella pneumophila, this paper will discuss factors influencing L. pneumophila growth. This will highlight the systemic nature of changes to water chemistry and public health impacts. As we critically analyze these important aspects of water research, we offer discussions to stimulate future water quality research from a new and systemic perspective to inform and guide public health decision-making.


Overview of the wisdom stakeholder workshop on restoration management.
A Workshop to extend the Involvement of Stakeholders in Decisions On restoration Management (WISDOM) was held at New College, Oxford from 15 to 17 September 2003. The aim was to promote awareness and interest in the wider application of stakeholder involvement in the formulation of strategies for the management of contaminated agricultural land and produce following a nuclear accident. The workshop, through 25 plenary papers and a set of two facilitated discussion sessions, provided valuable feedback on a wide range of issues including technical and social factors affecting countermeasure selection, acceptability of intervention levels, the challenges of rural waste disposal and crisis management. The workshop achieved its aim and the findings will be disseminated widely. Stakeholder groups are already active in the UK, Finland, Belgium, France and Greece; there was commitment from participants to establish further, similar groups in other member states within the European Union.


[The evaluation of economic damage due to premature mortality of population of the Republic of Sakha (Yakutia)].
The evaluation of economic damage was implemented in relation to premature mortality of population of the Republic of Sakha (Yakutia), the region with particular social economic and natural climatic conditions specific to territories of the North. The calculation of economic damage is based on methodology proposed by number of ministries of the Russian Federation and Rosstat in 2012. The presented evaluations and analysis of materials give an idea about total amount of economic damage because of mortality of population of the Republic of Sakha (Yakutia) which is necessary to consider during development of regional programs of decreasing of population mortality.


α7β1 Integrin regulation of gene transcription in skeletal muscle following an acute bout of eccentric exercise.
The α7β1 integrin is concentrated at the costameres of skeletal muscle and provides a critical link between the actin cytoskeleton and laminin in the basement membrane. We previously demonstrated that expression of the α7BX2 integrin subunit (MCK:α7BX2) preserves muscle integrity and enhances myofiber cross-sectional area following eccentric exercise. The purpose of this study was to utilize gene expression profiling to reveal potential mechanisms by which the α7BX2-integrin contributes to improvements in muscle growth after exercise. A microarray analysis was performed using RNA extracted from skeletal muscle of wild-type or transgenic mice under sedentary conditions and 3 h following an acute bout of downhill running. Genes with false discovery rate probability values below the cutoff of P < 0.05 (n = 73) were found to be regulated by either exercise or transgene expression. KEGG pathway analysis detected upregulation of genes involved in endoplasmic reticulum protein processing with integrin overexpression. Targeted analyses verified increased transcription of Rpl13a, Nosip, Ang, Scl7a5, Gys1, Ndrg2, Hspa5, and Hsp40 as a result of integrin overexpression alone or in combination with exercise (P < 0.05). A significant increase in HSPA5 protein and a decrease in CAAT-enhancer-binding protein homologous protein (CHOP) were detected in transgenic muscle (P < 0.05). In vitro knockdown experiments verified integrin-mediated regulation of Scl7a5 The results from this study suggest that the α7β1 integrin initiates transcription of genes that allow for protection from stress, including activation of a beneficial unfolded protein response and modulation of protein synthesis, both which may contribute to positive adaptations in skeletal muscle as a result of engagement in eccentric exercise.


Arthritis in Whipple's disease.
Synovial fluid and membranes were studied in two patients with Whipple's disease. In the first, arthrocentesis revealed 28,350 white blood cells/mm3, 96% of which were polymorphonuclear leukocytes. A dense neutrophilic infiltrate, periodic acid-Schiff, positive macrophages and bacilliform structures were present in the synovial membrane. The synovial fluid and membrane findings in the second case, and during intercritical periods in the first case, showed mild to moderate nonspecific inflammation. Since polyarthritis and other systemic manifestations often precede the gastrointestinal features of Whipple's disease by many years, a closed synovial membrane biopsy should be obtained in the appropriate clinical setting.


The evolving continuum of dysglycaemia: Non-diabetic hyperglycaemia in older adults.
Identifying non-diabetic hyperglycaemia (NDH) and intervening to halt the progression to type 2 diabetes has become an essential component of cardiovascular and cerebrovascular risk reduction. Diabetes prevention programs have been instigated to address the increasing prevalence of NDH and type 2 diabetes by targeting lifestyle modifications. Evidence suggests that the risk of progression from NDH to type 2 diabetes declines with age, and that a diagnosis of type 2 diabetes in older adults is not associated with the same risk of adverse consequences as it is in younger age groups. The current definition of NDH is not adjusted based on a person's age. Therefore, there is debate about the emphasis that should be placed upon a diagnosis of NDH in older adults. This article will explore the evidence and current clinical practice surrounding dysglycaemia through the spectrum of different age ranges, and the potential implications this has for older adults.


Crystal structure of a bacterial ribonuclease P RNA.
The x-ray crystal structure of a 417-nt ribonuclease P RNA from Bacillus stearothermophilus was solved to 3.3-A resolution. This RNA enzyme is constructed from a number of coaxially stacked helical domains joined together by local and long-range interactions. These helical domains are arranged to form a remarkably flat surface, which is implicated by a wealth of biochemical data in the binding and cleavage of the precursors of transfer RNA substrate. Previous photoaffinity crosslinking data are used to position the substrate on the crystal structure and to identify the chemically active site of the ribozyme. This site is located in a highly conserved core structure formed by intricately interlaced long-range interactions between interhelical sequences.


[Possibilities and limitations of life span changes in laboratory experiment].
The article shows the results of set of experiments with laboratory strains of Musca domestica L. demonstrating high level of polymorphism and differentiation in the initial population (strain Cooper) by sign of adults' life span (LS). Possibility of LS indices extension as a consequence of hormesis caused by a short-term contact with the toxic compound (piperonylbutoxide) has been illustrated. Limitations of LS changes defined by species genotype characteristics have been established.