Effect and Stability of Poly(Amido Amine)-Induced Biomineralization on Dentinal Tubule Occlusion.
In recent years, scientists have developed various biomaterials to remineralize human teeth to treat dentine hypersensitivity. Poly(amido amine) (PAMAM) dendrimers have become a research focus in this field. It has been demonstrated that PAMAM is able to create precipitates both on the surface of and within the dentinal tubules, however, there is little information about its effect on reducing dentine permeability in vitro. This study aimed to evaluate the in vitro effectiveness and stability of the fourth generation amine-terminated PAMAM on dentinal tubule occlusion, especially on dentine permeability. Sodium fluoride (NaF), which has been widely used as a desensitizing agent, is regarded as positive control. Demineralized sensitive dentine samples were coated with PAMAM or sodium fluoride solutions and soaked in artificial saliva (AS) at 37 °C for different periods. Four weeks later, samples in each group were then equally split into two subgroups for testing using a brushing challenge and an acid challenge. Dentine permeability of each specimen was measured before and after each challenge using a fluid filtration system. Dentine morphology and surface deposits were characterized by scanning electron microscope (SEM) and analyzed with Image-Pro Plus software. Data were evaluated through multifactorial ANOVA with repeated measures and pair-wise comparisons at a level of 5%. The results showed that PAMAM and NaF significantly reduced dentine permeability to 25.1% and 20.7%. Both of them created precipitates on dentine surfaces after AS immersion for 28 days. PAMAM-induced biomineralization not only on dentine surfaces, but also deeper in dentinal tubules, significantly reduced dentine permeability. Moreover, PAMAM-induced biomineralization elicited excellent stable occlusion effects after acid challenge. In conclusion, PAMAM demonstrated a strong ability to resist acid and showed great potential to be used in the treatment of dentine hypersensitivity in future.


Diversity, abundance and novel 16S rRNA gene sequences of methanogens in rumen liquid, solid and epithelium fractions of Jinnan cattle.
Three methanogen 16S rRNA gene clone libraries were constructed from liquid (LM), solid (SM) and epithelium (EM) fractions taken from the rumen of Jinnan cattle in China. After the amplification by PCR using methanogen-specific primers Met86F and Met1340R, equal quantities of PCR products from the same fractions from each of the four cattle were mixed together and used to construct the three libraries. Sequence analysis showed that the 268 LM clones were divided into 35 phylotypes with 18 sequences of phylotypes affiliated with the genus Methanobrevibacter (84.3% of clones). The 135 SM clones were divided into 19 phylotypes with 11 phylotypes affiliated with the genus Methanobrevibacter (77.8%). The 267 EM clones were divided into 33 phylotypes with 15 phylotypes affiliated with the genus Methanobrevibacter (77.2%). Clones closely related to Methanomicrobium mobile and Methanobrevibacter wolinii were only found in the LM library, and those to Methanobrevibacter ruminantium and Methanobrevibacter gottschalkii only in the SM library. LM library comprised 12.4% unidentified euryarchaeal clones, SM library 23.7% and EM library 25.5%, respectively. Five phylotypes (accession number: EF055528 and EF055531-EF055534) did not belong to the Euryarchaeota sequences we had known. One possible new genus (represented by phylotype E17, accession number EF055528) belonging to Methanobacteriaceae was identified from EM library. Quantitative real-time PCR for the first time revealed that epithelium fraction had significantly higher density of methanogens, with methanogenic mcrA gene copies (9.95 log 10 (copies per gram of wet weight)) than solid (9.26, P < 0.01) and the liquid (8.44, P < 0.001). The three clone libraries also appeared different in Shannon index (EM library 2.12, LM library 2.05 and SM library 1.73). Our results showed that there were apparent differences in the methanogenic diversity and abundance in the three different fractions within the rumen of Jinnan cattle, with Methanobrevibacter species predominant in all the three libraries and with epithelium fraction having more unknown species and higher density of methanogens.


[Urothelial carcinoma of the upper urinary tract. Survival and prognostic factors].
To analyze the survival and the main prognostic factors in patients with transitional cell carcinoma of the upper urinary tract. From 1983 to 1996, we treated 50 patients with transitional cell carcinoma of the upper urinary tract. Treatment was basically conservative except in those cases whose tumor stage or grade required a radical approach. Grading and staging were performed according to the 1992 TNM classification. Eighteen patients had died at one year mean follow-up., At the time the study was completed (June, 1997), 32 patients were alive with a mean follow-up of 4.9 years. Disease-free survival, overall and specific survival were analyzed according to sex, age, association with bladder tumors, localization, type of treatment, tumor size, number, histological grade and stage. The male-to-female ratio was 5:1. Patient mean age was 65.7 years. Association with bladder tumors was observed in 50%. Treatment was conservative in 40% and radical in 60%. The five- and ten-year disease-free survival rates were 69%, overall survival 61% and specific survival 71%. The univariate analysis showed the following to be unfavorable prognostic factors for survival: renal vs ureteral tumors, radical vs conservative treatment, high grade and stage tumors. The association of carcinoma in situ with other tumors of the upper urinary tract was also found to be an unfavorable factor for disease-free survival. The multivariate analysis associated T4 and G3 tumors with poor prognosis. Transitional cell carcinoma of the upper urinary tract was associated with bladder tumors in 50% of the cases. Low grade stage tumors demonstrated a high survival rate, therefore conservative treatment should be the first approach. High grade/ stage tumors were found to be unfavorable prognostic factors for survival.


The effect of intracanal Ledermix on root resorption of delayed-replanted monkey teeth.
Progressive root resorption is one of the common sequelae in replanted teeth, which is detrimental to their long-term prognosis. Ledermix paste, with its composition of triamcinolone acetonide and demethylclortetracycline, has been shown to inhibit inflammation and the associated hard tissue resorption. This study evaluated the effect of immediate intracanal Ledermix on root resorption of delayed-replanted monkey teeth. A total of 36 roots were root canal treated. For the experimental group, intracanal Ledermix was placed prior to extraction and replantation after 1-h bench dry. The positive control group was root filled and replanted after 1 h while the negative control group was root filled and replanted immediately. The monkeys were sacrificed after 12 weeks. The H&E histological tissue specimens were prepared and evaluated using a method modified from that of Andreasen's morphometric analysis, as favorable or complete healing and unfavorable healing, comprising inflammatory root resorption and replacement resorption. The results were analyzed using Kruskal-Wallis and Mann-Whitney U-tests as well as Wilcoxon signed ranks test. The negative control group produced highly significant favorable healing and unfavorable healing as compared to the Ledermix group (P = 0.000). The Ledermix group only showed significantly higher occurrence of complete healing (35.46%) compared to the positive control group (16.58%) (P = 0.037) but there were no significant differences in the inflammatory root resorption and replacement resorption. Nevertheless, when the latter two unfavorable healing patterns were combined, there was a significantly lower overall unfavorable healing in the Ledermix group (64.54%) when compared to the positive control group (83.43%) (P = 0.037). This unfavorable healing outcome in the Ledermix group, however, was not significantly different from the favorable healing outcome with the same treatment modality (P = 0.110).


A novel high specific surface area conducting paper material composed of polypyrrole and Cladophora cellulose.
We present a novel conducting polypyrrole-based composite material, obtained by polymerization of pyrrole in the presence of iron(III) chloride on a cellulose substrate derived from the environmentally polluting Cladophora sp. algae. The material, which was doped with chloride ions, was molded into paper sheets and characterized using scanning and transmission electron microscopy, N 2 gas adsorption analysis, cyclic voltammetry, chronoamperometry and conductivity measurements at varying relative humidities. The specific surface area of the composite was found to be 57 m (2)/g and the fibrous structure of the Cladophora cellulose remained intact even after a 50 nm thick layer of polypyrrole had been coated on the cellulose fibers. The composite could be repeatedly used for electrochemically controlled extraction and desorption of chloride and an ion exchanging capacity of 370 C per g of composite was obtained as a result of the high surface area of the cellulose substrate. The influence of the oxidation and reduction potentials on the chloride ion exchange capacity and the nucleation of delocalized positive charges, forming conductive paths in the polypyrrole film, was also investigated. The creation of conductive paths during oxidation followed an effective medium rather than a percolative behavior, indicating that some conduction paths survive the polymer reduction steps. The present high surface area material should be well-suited for use in, e.g., electrochemically controlled ion exchange or separation devices, as well as sensors based on the fact that the material is compact, light, mechanically stable, and moldable into paper sheets.


Relationship between Pathological Characteristics and Radiological Findings on Perfusion MR Imaging of Meningioma.
Few studies have reviewed the roles of perfusion magnetic resonance (MR) imaging in the histopathological examination of meningiomas. We analyzed the relationships between radiological findings on perfusion MR imaging and pathological characteristics such as origin of the tumor, mitotic activity, pathological subtype, and perifocal edema formation. The subjects were 21 surgical cases of meningioma preoperatively evaluated by perfusion MR imaging. A region of interest (ROI) was set inside of the tumor, and perifocal edema of the same size, cerebral blood volume (CBV), and cerebral blood flow (CBF) on perfusion MR and diffusion-weighted (DW) imaging were analyzed. These radiological data were evaluated in comparison with histopathological characteristics. On perfusion MR imaging, the average ratio of CBV against the contralateral side was 6.43 (1.13-20.0) and that of CBF was 7.73 (1.34-11.3). There was no significant relationship with perfusion MR imaging data, tumor volume, or perifocal edema volume. However, the large peritumoral edema group often had a higher CBV and CBF than the non-large peritumoral edema group. The skull base group had a significantly higher CBV and lower signal intensity on DW images than the non-skull base group. Signal intensity on DW images was higher in grade II or III than in grade I. Perfusion MR imaging data revealed that the higher ratio of peritumoral edema against tumor size was associated with higher blood flow and blood volume under intratumoral circulatory conditions, and that skull base meningioma had a higher blood volume than non-skull base meningioma.


Evaluation of differences and dosimetric influences of beam models using golden and multi-institutional measured beam datasets in radiation treatment planning systems.
The beam model in radiation treatment planning systems (RTPSs) plays a crucial role in determining the accuracy of calculated dose distributions. The purpose of this study was to ascertain differences in beam models and their dosimetric influences when a golden beam dataset (GBD) and multi-institution measured beam datasets (MBDs) are used for beam modeling in RTPSs. The MBDs collected from 15 institutions, and the MBDs' beam models, were compared with a GBD, and the GBD's beam model, for Varian TrueBeam linear accelerator. The calculated dose distributions of the MBDs' beam models were compared with those of the GBD's beam model for simple geometries in a water phantom. Calculated dose distributions were similarly evaluated in volumetric modulated arc therapy (VMAT) plans for TG-119 C-shape and TG-244 head and neck, at several dose constraints of the planning target volumes (PTVs), and organs at risk. The agreements of the MBDs with the GBD were almost all within ±1%. The calculated dose distributions for simple geometries in a water phantom also closely corresponded between the beam models of GBD and MBDs. Nevertheless, there were considerable differences between the beam models. The maximum differences between the mean energy of the energy spectra of GBD and MBDs were -0.12 MeV (-10.5%) in AcurosXB (AXB, Eclipse) and 0.11 MeV (7.7%) in collapsed cone convolution (CCC, RayStation). The differences in the VMAT calculated dose distributions varied for each dose region, plan, X-ray energy, and dose calculation algorithm. The ranges of the differences in the dose constraints were -5.6% to 3.0% for AXB and -24.1% to 2.8% for CCC. In several VMAT plans, the calculated dose distributions of GBD's beam model tended to be lower in high-dose regions and higher in low-dose regions than those of the MBDs' beam models. We found that small differences in beam data have large impacts on the beam models, and on calculated dose distributions in clinical VMAT plan, even if beam data correspond within ±1%. GBD's beam model was not a representative beam model. The beam models of GBD and MBDs and their calculated dose distributions under clinical conditions were significantly different. These differences are most likely due to the extensive variation in the beam models, reflecting the characteristics of beam data. The energy spectrum and radial energy in the beam model varied in a wide range, even if the differences in the beam data were <±1%. To minimize the uncertainty of the calculated dose distributions in clinical plans, it was best to use the institutional MBD for beam modeling, or the beam model that ensures the accuracy of calculated dose distributions.


Understanding the Value of International Research Networks: An Evaluation of the International Cancer Screening Network of the US National Cancer Institute.
International research networks have the potential to accelerate scientific progress via knowledge sharing and collaboration. In 2018, the US National Cancer Institute evaluated the International Cancer Screening Network (ICSN), in operation since 1988. ICSN hosts a biennial scientific meeting and scientific working groups. A survey was fielded to 665 ICSN participants, and a bibliometric analysis was conducted for ICSN publications. A total of 243 individuals completed the survey (36.5%). They reported that participating in the ICSN helped advance their knowledge of cancer screening research (75.7%), policy development (56%), and implementation (47.7%). Approximately three-quarters agreed that ICSN facilitated knowledge sharing and networking among researchers and implementers (79.9%) and those working on different continents (74.0%) and cancer sites (73.7%). More than half reported that participating helped them form new collaborations in screening implementation (58.0%) or research (57.6%). Most agreed that ICSN helped to advance screening research and evaluation (75.4%), effective screening practices (71.2%), and screening policies (60.9%). Many reported that participating informed advances in their own research (68.7%) and screening implementation (50.2%) and policies (49.4%) in their settings. Approximately two-thirds agreed that ICSN helped advance career development among current experts (66.6%) and train the next generation (62.2%). Half (51.4%) reported that participating advanced their own careers. The 20 ICSN publications included 75 coauthors. They were cited in 589 publications with more than 2,000 coauthors. Findings provide evidence of the influence of ICSN on international knowledge dissemination, collaboration, and advances in cancer screening research, implementation, and policies and highlight the potential value of longstanding international research networks.


L-dopa-responsive movement disorder caused by Nocardia asteroides localized in the brains of mice.
Nocardia asteroides can cause infections in the brain of humans and a variety of animals. In mice, invasion of the central nervous system results in specific neurologic signs. Following intravenous injection of various doses of log-phase N. asteroides GUH-2 into female BALB/c mice, localization and growth of nocardial cells within the brains were determined, histopathological sections were prepared, and Nissl substance and tyrosine hydroxylase immunoreactivity were observed. Mice were monitored for the development of neurologic signs, and their responsiveness to L-dopa was determined. It was shown that nocardial cells became localized within specific regions of the brain and then underwent rapid growth followed by a delayed clearance, and there was no inflammatory response at the site of invasion for 24 h. Mice that received a subclinical dose of nocardiae developed specific neurologic signs that emerged following the elimination of nocardial cells from the brain. On the basis of the specific signs, mice could be divided into distinct groups. One group consisted of animals that had a form of hemiparesis that did not respond to L-dopa. They expressed a deviation of the head and a tendency to roll, and when suspended by the tail they would spin rapidly. The second group of mice developed a rhythmic, uncontrolled vertical shake of the head (four to five times per s) tremulous movement, stooped posture, restlessness, and no signs of hemiparesis. The head shakes were temporarily stopped by treatment with L-dopa. Mice that expressed head shakes had a loss of Nissl substance and tyrosine hydroxylase immunoreactivity in the neurons of the substantia nigra and ventral tegmental areas of the brain. Hyaline inclusion bodies that resembled Lewy bodies were found in the neurons of mice with head shake 1 month after infection. Therefore, mice infected with N. asteroides may serve as a model for studying parkinsonian signs and other degenerative diseases involving extrapyramidal and pyramidal systems.


Nanoparticle Polymers Influence on Cardiac Health: Good or Bad for Cardiac Physiology?
Cardiovascular diseases (CVD) are one of the leading causes of death and morbidity worldwide. Lifestyle modifications, medications, and addressing epidemiological factors have long been at the forefront of targeting therapeutics for CVD. Treatments can be further complicated given the intersection of gender, age, unique comorbidities, and healthcare access, among many other factors. Therefore, expanding treatment and diagnostic modalities for CVD is absolutely necessary. Nanoparticles and nanomaterials are increasingly being used as therapeutic and diagnostic modalities in various disciplines of biomedicine. Nanoparticles have multiple ways of interacting with the cardiovascular system. Some of them alter cardiac physiology by impacting ion channels, whereas others influence ions directly or indirectly, improving cellular death via decreasing oxidative stress. While embedding nanoparticles into therapeutics can help enhance healthy cardiovascular function in other scenarios, they can also impair physiology by increasing reactive oxidative species and leading to cardiotoxicity. This review explores different types of nanoparticles, their effects, and the applicable dosages to create a better foundation for understanding the current research findings.


Lgl/aPKC and Crb regulate the Salvador/Warts/Hippo pathway.
A key goal of developmental biology is to understand the mechanisms that coordinate organ growth. It has long been recognized that the genes that control apico-basal cell polarity also regulate tissue growth. How loss of cell polarity contributes to tissue overgrowth has been the subject of much speculation. Do loss-of-function mutations in cell polarity regulators result in secondary effects that globally deregulate cell proliferation, or do these genes specifically control growth pathways? Three recent papers have shown that the apico-basal polarity determinants Lgl/aPKC and Crb regulate tissue growth independently of their roles in cell polarity and coordinately regulate cell proliferation and cell death via the Salvador/Warts/Hippo (SWH) pathway. Lgl/aPKC are required for the correct localization of Hippo (Hpo)/Ras associated factor (RASSF), while Crb regulates the levels and localization of Expanded (Ex), indicating that cell polarity determinants modify SWH pathway activity by distinct mechanisms. Here, we review the key data that support these conclusions, highlight remaining questions and speculate on the underlying mechanisms by which the cell polarity complexes interact with the SWH pathway. Understanding the interactions between cell polarity regulators and the SWH pathway will improve our knowledge of how epithelial organization and tissue growth are coordinated during development and perturbed in disease states such as cancer.


Environmental factors and cancer mortality in Italy: correlational exercise.
Mortality rates for 21 cancer sites in 20 Italian regions have been correlated with several economic and dietary variables (including alcohol and coffee consumption), patterns of cigarette smoking and reproductive habits. In both sexes, a large number of strong correlations emerged, the most notable ones being the strong positive coefficients between cigarettes sold in the early 1950s and lung cancer mortality in middle-aged males in the early 1970s, between gross internal product or meat consumption and cancer of the intestines in both sexes, between total per caput consumption and cancer of the prostate and between mean age at first birth, gross internal product and milk consumption and cancer of the breast. Cancer of the ovary was positively correlated with mean age at the first birth, and negatively with average number of births. Among the unexpected correlations observed, the most remarkable ones were the strong positive coefficient between skin cancer mortality and latitude (which can however be explained in terms of different constitutional characteristics of skin color in various Italian regions), and the pattern of coefficients emerging for gastric cancer, showing positive correlations with gross internal product or meat and negative ones with bread, pasta or fish. These and other results (including the analysis of several first-order partial correlation coefficients) are discussed with regard to their limitations and major points of interest, and in comparison with similar studies conducted on different populations.


Trauma centrality and PTSD in veterans returning from Iraq and Afghanistan.
Research has demonstrated that the extent to which an individual integrates a traumatic event into their identity ("trauma centrality") positively correlates with posttraumatic stress disorder (PTSD) symptom severity. No research to date has examined trauma centrality in individuals exposed to combat stress. This study investigated trauma centrality using the abridged Centrality of Event Scale (Berntsen & Rubin, 2006) among Operation Enduring Freedom/Operation Iraqi Freedom combat veterans (n = 46). Multiple regression analyses demonstrated that trauma centrality predicted PTSD symptoms. Trauma centrality and PTSD symptoms remained significantly correlated when controlling for depression in subgroups of veterans with or without probable PTSD. This study replicates and extends findings that placing trauma at the center of one's identity is associated with PTSD symptomatology.


NFATC2 Modulates Radiation Sensitivity in Dermal Fibroblasts From Patients With Severe Side Effects of Radiotherapy.
Although it is well established that 5 to 15% of radiotherapy patients exhibit severe side-effects in non-cancerous tissues, the molecular mechanisms involved are still poorly known, and the links between cellular and tissue radiosensitivity are still debated. We here studied fibroblasts from non-irradiated skin of patients with severe sequelae of radiotherapy, to determine whether specific basal cell activities might be involved in susceptibility to side-effects in normal tissues. Compared to control cells, patient fibroblasts exhibited higher radiosensitivity together with defects in DNA repair. Transcriptome profiling of dermal fibroblasts from 16 radiotherapy patients with severe side-effects and 8 healthy individuals identified 540 genes specifically deregulated in the patients. Nuclear factor of activated T cells 2 (NFATC2) was the most differentially expressed gene, poorly expressed at both transcript and protein level, whereas the NFATC2 gene region was hypermethylated. Furthermore, NFATC2 expression correlated with cell survival after irradiation. Finally, silencing NFATC2 in normal cells by RNA interference led to increased cellular radiosensitivity and defects in DNA repair. This study demonstrates that patients with clinical hypersensitivity also exhibit intrinsic cellular radiosensitivity in their normal skin cells. It further reveals a new role for NFATC2 as a potential regulator of cellular sensitivity to ionizing radiation.


Theory for bowtie plasmonic nanolasers.
We develop a fundamental formulation for electrically-pumped plasmonic semiconductor nanolasers based on a metallic bowtie structure. Because of the negative dielectric constant of the metal at optical frequencies, the effective modal volume of the plasmonic mode can be compressed to the nanometer scale. In addition, the curvature effect of the bowtie tips provides additional field enhancement in the bowtie gap and further reduces the modal volume. With this small modal volume, the required volume of the active region is reduced correspondingly, which significantly decreases the threshold current. The huge field enhancement due to the small modal volume at the gap of the bowtie may overcome the material and radiation losses by increasing both the spontaneous and stimulated emission rates, and it makes the lasing action possible.


Ma Huang, du complement alimentaire a l'abus.
Dietary supplements containing Ma Huang (chinease ephedra) are available on the web sites and dietary shops in USA. They are widely promoted and used as a mean of weight reduction and energy enhancement. They contain Ma Huang alone or combined with Guarana (caffeine), creatine, St Jonh's wort, carnitine and are proposed with different labels. Numerous reports of adverse reactions and acute intoxication related to these products use were described in the medical literature. In the light of the severity of these cases, some of which resulted in permanent injury and death, the Food and Drug Administration has proposed limits on the dose and duration of use of such supplements. A review of 140 reports submitted to the FDA between June 1997 and March 1999, 47 % involved cardiovascular symptoms, 18 % neurological symptoms. Severe hypertension was the single most frequent adverse effect followed by tachycardia, myocardial infarction, stroke, seizure. Ten events resulted in death and 13 produced permanent impairment. In France, ampleness of the use of dietary supplements containing ephedra alkaloids is unknown. Two French recent severe poisonings (one with "ripped Fuel" for losing weight and the other with "Energy pills" in a body builder) show that there is serious health risks for the chronic users. Dietary supplements are not subject to control under "la Direction Générale de la Santé". Informations for general public, medical community and health-care authorities are necessary to be aware of potential health hazards of these products use.


Problems With Optimal Energy and Protein Delivery in the Pediatric Intensive Care Unit.
Optimal nutrition therapy (NT) delivery is associated with improved outcomes in critically ill children. However, avoidable barriers impede delivery of optimal energy and protein in the pediatric intensive care unit (PICU). This study aims to describe the gap between energy and protein prescription and actual intake. Single-center prospective cohort study, including consecutive children (age: 1 month to 15 years) admitted to the PICU in southern Brazil. Demographics, clinical characteristics, and NT details were recorded. We enrolled 130 patients: 37% female; median (interquartile range) age, 29.43 months (4.03, 100.63); PICU length of stay, 6 days (4, 13). Median predicted energy expenditure by Schofield equation and prescribed and actual energy intake were 47.13 kcal/kg/d (38.60, 55.38), 31.94 kcal/kg/d (13.99, 51.90), and 25.06 kcal/kg/d (10.21, 46.92), respectively. On average, actual energy intake was 47% of the predicted energy expenditure, and 68% of patients were underfed. Actual protein intake was 49% of the estimated requirement. NT was interrupted in 64% of patients. There were significant gaps among the predicted requirement, prescription, and actual delivery of energy and protein in the PICU. Suboptimal prescription and multiple feeding interruptions resulted in underfeeding.


Ochrobactrum intermedium septicemia.
Ochrobactrum species are emerging Gram-negative, non-fermenting bacteria with low virulence. Infection with the Ochrobactrum species is commonly nosocomial and has been reported in patients with indwelling medical devices and implants. Among the species of Ochrobactrum infecting humans, Ochrobactrum anthropic and Ochrobactrum intermedium are the commonest ones. We present a case of septicemia caused by Ochrobactrum intermedium in a 75-year-old patient with lower limb cellulitis. This report describes the epidemiology, clinical manifestations, laboratory diagnosis, antibiotic susceptibility pattern, and treatment of Ochrobactrum infections.


Duplicate publications: A sample of redundancy in the Journal of Urology.
: Redundant publications occur when authors publish a partial or complete duplicate of data from an existing manuscript. The push for academic advancement in medicine may result in redundant publications that erode the quality of literature. We sampled the extent of redundancy within the Journal of Urology. : Original articles published in the Journal of Urology in 2006 were reviewed. MEDLINE was used to identify suspected duplicate publications by combining the last names of the first, second and last authors with keywords provided by the article. Results were limited to 2004 to 2008. Two investigators reviewed the suspected duplicate publications and classified them as duplicate, probable duplicate and salami-slicing. : We screened 723 original articles. Of these original articles, 13 (1.8%) had some form of redundancy. One (0.1%) original article had a duplicate article, 5 (0.7%) original articles had probable duplicates, and 7 (1%) original articles were salami-sliced. The proportion of redundant articles published prior to, and following, their 2006 index article was 5/13 (38.5%) and 7/13 (53.8%), respectively. One duplicate (7.7%) was published in the same month as its index. : Detection of redundant publications is a laborious process for reviewers and editors. This sampling of the Journal of Urology revealed that the duplication rate in this journal is small, but significant. Further assessment of the urological literature is warranted.


Characterization and Clinical Impact of Bloodstream Infection Caused by Carbapenemase-Producing Enterobacteriaceae in Seven Latin American Countries.
Infections caused by carbapenem-resistant Enterobacteriaceae are a public health problem associated with higher mortality rates, longer hospitalization and increased healthcare costs. We carried out a study to describe the characteristics of patients with carbapenemase-producing Enterobacteriaceae (CPE) and non-CPE bloodstream infection (BSI) from Latin American hospitals and to determine the clinical impact in terms of mortality and antibiotic therapy. Between July 2013 and November 2014, we conducted a multicenter observational study in 11 hospitals from 7 Latin American countries (Argentina, Colombia, Ecuador, Guatemala, Mexico, Peru, Venezuela). Patients with BSI caused by Enterobacteriaceae were included and classified either as CPE or non-CPE based on detection of blaKPC, blaVIM, blaIMP, blaNDM and blaOXA-48 by polymerase chain reaction. Enrolled subjects were followed until discharge or death. Demographic, microbiological and clinical characteristics were collected from medical records. Both descriptive and inferential statistics were used to analyze the information. A total of 255 patients with Enterobacteriaceae BSI were included; CPE were identified in 53 of them. In vitro non-susceptibility to all screened antibiotics was higher in the patients with CPE BSI, remaining colistin, tigecycline and amikacin as the most active drugs. Combination therapy was significantly more frequent in the CPE BSI group (p < 0.001). The most common regimen was carbapenem + colistin or polymyxin B. The overall mortality was 37% (94/255). Overall and attributable mortality were significantly higher in patients with CPE BSI (p < 0.001); however, we found that patients with CPE BSI who received combination therapy and those who received monotherapy had similar mortality. After multivariate adjustment, CPE BSI (adjusted odds ratio [aOR] 4; 95% confidence interval [CI] 1.7-9.5; p = 0.002) and critical illness (aOR 6.5; 95% CI 3.1-13.7; p < 0.001) were independently associated with in-hospital mortality. This study provides valuable data on the clinical characteristics and mortality risk factors in patients with CPE BSI. We determined that CPE infection is an independent mortality predictor and thus Latin American hospitals should perform campaigns on prevention and control of CPE BSI.


Shared decision-making in the care of individuals with diabetes.
People with diabetes often live with other chronic conditions and lead complicated lives. Determining what is the best management decision for a patient requires consideration of each individual's personal, social and biomedical context, what he or she values, the reasons he or she has to value the available options, and the relative contribution of each option in terms of benefits, harms, costs and inconveniences. Empathic conversations between patients and clinicians to diagnose the patient situation that necessitates action and the range of evidence-based actions that best address the situation, so-called shared decision-making, are essential to the personalized care of people with diabetes. The aim of the present review was to present key elements of shared decision-making and propose three different approaches for its application. The first approach focuses on transferring information to patients so that they can make decisions. The second approach, choice, focuses on cultivating the individual's ability to give voice to which choice is best for them. The third approach, conversation, establishes an empathic conversational environment through which the individual with diabetes and their clinician think and talk through how to address the problems of living with diabetes and related illnesses. These approaches are manifest in the design of evidence-based decision aids created to support shared decision-making. In randomized trials, decision aids can efficiently improve patient's knowledge, satisfaction, risk awareness, decisional conflict and involvement. Further research, however, is needed to better understand when and how to promote the empathic conversations, patient, clinician and service and policy contexts necessary to routinely implement shared decision-making in different at scale healthcare systems. In the interim, sufficient evidence and tools exist for persons with diabetes and their clinicians to gain expertise in making decisions together.


Emodin suppresses cadmium-induced osteoporosis by inhibiting osteoclast formation.
Environmental level of cadmium (Cd) exposure can induce bone loss. Emodin, a naturally compound found in Asian herbal medicines, could influence osteoblast/osteoclast differentiation. However, the effects of emodin on Cd-induced bone damage are not clarified. The aim of this study was to investigate the role of emodin on Cd-induced osteoporosis. Sprague-Dawley male rats were divided into three groups which were given 0mg/L, 50mg Cd/L and 50mg Cd/L plus emodin (50mg/kg body weight). Bone histological investigation, microCT analysis, metabolic biomarker determination and immunohistochemical staining were performed at the 12th week. The bone mass and bone microstructure index of rats treated with Cd were obviously lower than in control. Cd markedly enhanced the osteoclast formation compared with control. Emodin significantly abolished the Cd-induced bone microstructure damage (p<0.05), osteoclast formation and increase of tartrate-resistant acid phosphatase 5b level (p<0.05). Our data further showed that emodin attenuated the Cd-induced inhibition of osteoprotegerin expression and stimulation of receptor activator for nuclear factor-κ B ligand expression. Our data show that emodin suppresses the Cd-induced osteoporosis by inhibiting osteoclast formation.


Multicenter analysis of effect of high biologic effective dose on biochemical failure and survival outcomes in patients with Gleason score 7-10 prostate cancer treated with permanent prostate brachytherapy.
To investigate the biochemical control rates and survival for Gleason score 7-10 prostate cancer patients undergoing permanent prostate brachytherapy as a function of the biologic effective dose (BED). Six centers provided data on 5,889 permanent prostate brachytherapy patients, of whom 1,078 had Gleason score 7 (n = 845) or Gleason score 8-10 (n = 233) prostate cancer and postimplant dosimetry results available. The median prostate-specific antigen level was 7.5 ng/mL (range, 0.4-300). The median follow-up for censored patients was 46 months (range, 5-130). Short-term hormonal therapy (median duration, 3.9 months) was used in 666 patients (61.8%) and supplemental external beam radiotherapy (EBRT) in 620 (57.5%). The patients were stratified into three BED groups: <200 Gy (n = 645), 200-220 Gy (n = 199), and >220 Gy (n = 234). Biochemical freedom from failure (bFFF) was determined using the Phoenix definition. The 5-year bFFF rate was 80%. The bFFF rate stratified by the three BED groups was 76.4%, 83.5%, and 88.3% (p < 0.001), respectively. Cox regression analysis revealed Gleason score, prostate-specific antigen level, use of hormonal therapy, EBRT, and BED were associated with bFFF (p < 0.001). Freedom from metastasis improved from 92% to 99% with the greatest doses. The overall survival rate at 5 years for the three BED groups for Gleason score 8-10 cancer was 86.6%, 89.4%, and 94.6%, respectively (p = 0.048). These data suggest that permanent prostate brachytherapy combined with EBRT and hormonal therapy yields excellent bFFF and survival results in Gleason score 7-10 patients when the delivered BEDs are >220 Gy. These doses can be achieved by a combination of 45-Gy EBRT with a minimal dose received by 90% of the target volume of 120 Gy of (103)Pd or 130 Gy of (125)I.


A new agent for the control of spasticity.
In a preliminary controlled trial, CIBA 34,647-Ba, a gamma aminobutyric acid derivative, was found to be more effective than placebo in reducing spasticity due to spinal injuries. In an uncontrolled trial, 34,647-Ba also appeared more effective than diazepam. The intensity of spasticity was measured electromyographically by the amplitude of the stretch reflex at various velocities, and the results were correlated with those obtained by clinical assessment. 34,647-Ba was effective in both complete and incomplete spinal cord lesions and it is suggested that it has an action at the spinal level. No significant side-effects were encountered.


Force detection of nuclear magnetic resonance.
Micromechanical sensing of magnetic force was used to detect nuclear magnetic resonance with exceptional sensitivity and spatial resolution. With a 900 angstrom thick silicon nitride cantilever capable of detecting subfemtonewton forces, a single shot sensitivity of 1.6 x 10(13) protons was achieved for an ammonium nitrate sample mounted on the cantilever. A nearby millimeter-size iron particle produced a 600 tesla per meter magnetic field gradient, resulting in a spatial resolution of 2.6 micrometers in one dimension. These results suggest that magnetic force sensing is a viable approach for enhancing the sensitivity and spatial resolution of nuclear magnetic resonance microimaging.


Help Is Available: Supporting Mental Wellness Through Peer Health Navigation with Young Black Men Who Have Sex with Men with HIV.
Young black men who have sex with men (YBMSM) with HIV experience disproportionate rates of trauma, incarceration, poverty, racial discrimination, and homophobia. The synergistic effects of these adverse experiences, along with increased rates of mental health disorders, increase their risk for poor health. To address this need, the study authors adapted a current HIV service model to include a peer-health navigation intervention (WITH U) to attend to behavioral health, health literacy, linkage to services, and psychosocial support for YBMSM with HIV. This longitudinal, mixed-methods, nonexperimental study reports on the mental health burden among participants and the association between participation in WITH U and mental wellness outcomes. Participants (N = 65) were an average age of 25-26 years (mean = 25.48, standard deviation = 2.51). Over 25% of participants reported clinically significant depression and/or anxiety symptoms and nearly half the participants reported experiencing post-traumatic stress symptoms that were at least moderately difficult to handle. Quantitative analyses indicated no significant positive association between intervention engagement and mental health symptoms; however, reporting a greater number of depression symptoms was associated with attending fewer intervention sessions. Qualitative data analysis revealed that participants' mental wellness was positively impacted by participating in the intervention and that participants preferred to receive mental wellness support from peer health navigators (HNs) rather than licensed mental health professionals. Yet, peer HNs did not feel adequately prepared to address participants' mental wellness concerns. Increased training for peer HNs and development of a linkage process to more formalized mental health services with community input may strengthen mental wellness support.


A novel preparation method for organogels: high-speed homogenization and micro-irradiation.
The aim of this work was to prepare organogels of Carbopol 974P NF (C974) in PEG 400 by using a novel technique, high-speed homogenization followed by microwave heating. Triclosan (TCS) was used as a model drug. C974, at concentrations ranging between 2% and 4%, was dispersed in 25 ml of PEG 400, and the dispersion was homogenised for 5 min at 24,000 rpm. The dispersion was either heated at 80°C in water bath under mechanic stirring at 200 rpm or exposed to micro-irradiation (1,200 W/1 h) for 2 min. The formulations prepared with both methods performed a well-structured gel matrix characteristic at 3% and 4% of C974 concentrations. As the concentrations of the polymer increased, the elastic properties also increased. The viscosity profiles indicated a shear-thinning system. DSC data revealed that TCS was dissolved in gel. Skin accumulation ability of TCS had been improved by these novel organogels regardless of the preparation method. TCS was still microbiologically effective after the microwave process was applied. It was determined that microwave heating is a suitable method to obtain C974 organogels. This novel production technique developed might be promising especially in industrial scale when the dramatic reduction in the preparation time and energy were considered.


Toxic alcohol ingestion: prompt recognition and management in the emergency department [digest].
Identifying patients with potential toxic alcohol exposure and initiating appropriate management is critical to avoid significant patient morbidity. Sources of toxic alcohol exposure include ethylene glycol, methanol, diethylene glycol, propylene glycol, and isopropanol. Treatment considerations include the antidotes fomepizole and ethanol, and hemodialysis for removal of the parent compound and its toxic metabolites. Additional interventions include adjunctive therapies that may improve acidosis and enhance clearance of the toxic alcohol or metabolites. This issue reviews common sources of alcohol exposure, basic mechanisms of toxicity, physical examination and laboratory findings that may guide rapid assessment and management, and indications for treatment. [Points & Pearls is a digest of Emergency Medicine Practice].


Establishing the cause of memory loss in older people.
Common causes of memory loss in older people are mild cognitive impairment, the various types of dementia, and psychiatric illness, mainly depression. Around 10% of patients with mild cognitive impairment progress to dementia each year. Alzheimer's disease accounts for 60-80% of cases. Other common types of dementia are vascular, fronto-temporal, Lewy body, Parkinson's, and mixed type dementia. There is evidence to suggest that dementia pathology is established before the onset of symptoms, and thus mild cognitive impairment can be considered as a predementia stage. NICE guidance suggests examination of: attention, concentration, short- and long-term memory, praxis, language and executive function. Particular attention should be paid to any signs of neglect, state of dress, agitation or poor attention. Dysphasia and difficulty in naming objects is often present. Mood symptoms (including suicidal ideation) may be primary or comorbid. Abnormal thoughts and perceptions should be probed for, as psychotic symptoms are common. Primary care options for cognitive testing include the General Practitioner Assessment of Cognition or the Abbreviated Mental Test Score. Physical examination should include observation of gait, inspection for tremor; examination for rigidity, bradykinesia, frontal release signs, upper motor neurone lesions, pulse and BP. Structural brain imaging can improve diagnostic accuracy, exclude other pathologies and act as a prognostic marker of dementia progression but the overlap in structural changes between the dementias makes imaging alone insufficient for diagnostic purposes. NICE guidelines recommend referral to a memory clinic for patients with mild cognitive impairment, those at high risk of dementia, such as patients with learning disabilities, Parkinson's disease, or patients who have had several strokes.


The essential oil of Kochia scoparia (L.) Schrad. as a potential repellent against stored-product insects.
Chemical composition of the essential oil from Kochia scoparia (L.) Schrad. (syn. Bassia scoparia (L.) A. J. Scott) was analyzed in quality and quantity by GC-MS and GC-FID. Repellent activities of the essential oil from K. scoparia (KSEO) were evaluated against two common species of stored-product insects Tribolium castaneum Herbst and Liposcelis bostrychophila Badonnel. Results indicated that KSEO mainly consisted of eugenol, β-caryophyllene, and α-humulene, accounting for 75.6%, 8.2%, and 1.4% of the total oil, respectively. KSEO and the three major components were repellent to T. castaneum and L. bostrychophila adults. Notably, KSEO exerted significant effects, comparable to the positive control DEET at 2 and 4 h post-exposure. Eugenol at 63.17-2.53 nL/cm2 exhibited high percentage repellency ranging from 96 to 70% against L. bostrychophila during 4-h exposure. To gain further insights into the repellent activity, molecular docking simulation was performed with eugenol as the ligand and an odorant binding protein TcOBPC12 (gene: TcOBP10B) from the model insect T. castaneum as the receptor. Docking calculation results revealed that TcOBPC12 had binding affinity to eugenol (△G = - 4.52 kcal/mol) along with a hydrogen bond of 0.18 nm (1.8 Å) long forming between them, which could be an important target protein associated with identifying volatile repellent molecules. This work highlights the promising potential of KSEO as a botanical repellent for controlling stored-product insects.


[Flow dynamics analysis in patients with a ruptured middle cerebral artery aneurysm. A case report].
Despite advancement of diagnostic and treatment modalities, subarachnoid hemorrhage (SAH) is still an entity of neurosurgical emergency with poor outcome. Recent reports indicated that hemodynamic stress might play an important role in rupture or the growth of cerebral aneurysms, but there is no consensus about how or which hemodynamic factor contribute to this phenomenon. In this report, magnetic resonance (MR)-based flow dynamics analysis was performed for a patient with SAH and the data obtained were directly compared with intraoperative findings. This 74-year-old woman was admitted for sudden onset headache. Head computed tomography scan showed SAH on the right sylvian fissure and intracerebral hematoma on the right temporal tip. Digital subtraction angiography showed a right middle cerebral artery aneurysm, which was considered to be the ruptured one. The aneurysm had two blebs, and the bleb around the aneurysm tip was exposed to low magnitude and high oscillation of wall shear stress (WSS). On the other hand, another bleb was exposed to high magnitude and low oscillation of WSS. Next day, the patient underwent open surgery and intraoperative findings showed the aneurysm tip was the ruptured point. MR-based flow dynamics analysis might be a useful diagnostic modality for patients with SAH. Although low magnitude and high oscillation of WSS might contribute to the aneurysm rupture, further case accumulation is necessary to reach a conclusion whether or not this is so.


Analysis of transcription of the human Alu family ubiquitous repeating element by eukaryotic RNA polymerase III.
A series of clones that contain human Alu family elements are actively transcribed in soluble in vitro RNA polymerase III systems. The 5' ends of the in vitro transcripts are located about 170 nucleotides upstream of the eponymous Alu I site of the repeat, while a region associated with specifying of the initiation site for in vitro transcription lies in the region between 79 and 106 nucleotides upstream of the central Alu site. Thus, the RNA polymerase III transcription unit defined by the human Alu family is similar to other RNA polymerase III transcription units in possessing an internal region that is required for active transcription in vitro.


Monoclonal antibodies to gp100 inhibit penetration of human herpesvirus 6 and polykaryocyte formation in susceptible cells.
We report the derivation and properties of a monoclonal antibody (MAb 2E4) which neutralizes human herpesvirus 6 (HHV-6). MAb 2E4 precipitated from lysates of infected cells a glycosylated polypeptide 100,000 in apparent molecular weight and minor components of 80,000, and 32,500. The predominant reactive protein after a pulse was the 100,000-molecular-weight peptide designated as gp100. The smaller polypeptides appeared in the precipitate predominantly after a chase. MAb 2E4 neutralized HHV-6 infectivity in the presence and in the absence of complement, and it inhibited the penetration of virus into the cells. Addition of MAb 2E4 as late as 6 h postinfection inhibited the formation of large polykaryocytes typical of HHV-6-infected cells.


Ten years' research on a cardiovascular tonic: a comprehensive approach-from quality control and mechanisms of action to clinical trial.
Objective. Mortality arising from cardiovascular pathologies remains one of the highest. Maintenance of cardiovascular health therefore remains a universal concern. Interventional therapies and medications have made impressive advances, but preventive measures would be of the same importance. Method. Ten years' search for a simple herbal formula has resulted in a two-herb combination, consisting of Salviae Miltiorrhizae Radix et Rhizoma and Puerariae Lobatae Radix. The formula has been studied extensively on cardiovascular biological platforms and then put on three clinical trials. Results. In the laboratory, the formula was found to have the biological effects of anti-inflammation, anti-oxidation, anti-foam cell formation on vascular endothelium, and vasodilation. Clinical trials using ultrasonic carotid intima thickness as a surrogate marker showed very significant benefits. No significant adverse effects were encountered. Conclusion. It is therefore recommended that the herbal formula could be used as an adjuvant therapy in cardiac patients under treatment or as a preventive agent among the susceptible.


MeCP2 regulates GFAP expression within the developing brain.
Mutations in MECP2 cause Rett syndrome (RTT), an X-linked neurodevelopmental disorder that primarily affects females. Individuals with RTT have increased glial fibrillary acidic protein (GFAP) expression in the brain. GFAP is an intermediate filament protein that is expressed predominately within astrocytes in the CNS. MeCP2 binds to methylated regions of the GFAP promoter region and suppresses GFAP expression in vitro. Therefore, we wanted to determine if transiently reducing MeCP2 expression would increase GFAP expression in the developing rat brain. Male and female rats received infusions of either MeCP2 or control siRNA targeting the amygdala during the first 3 days of postnatal life. Brains were collected after 6h or 2 weeks following the last infusion. MeCP2 siRNA increased GFAP mRNA and protein within the female, but not the male, amygdala on postnatal day (PN) 2. Two weeks following the infusion, levels returned to normal. MeCP2 siRNA targeting the hypothalamus also increases GFAP mRNA within the female hypothalamus on PN2, suggesting that the regulation is not brain region-specific. It appears that MeCP2 does not regulate all astrocyte markers in the developing female brain, but specifically regulates GFAP expression, as levels of S100β and vimentin were not altered in the female amygdala at either time point. These data contribute to the idea that the role of MeCP2 differs in the developing male versus female brain. Further elucidating the regulation and function of GFAP can contribute to our understanding of MeCP2 function and perhaps RTT etiology.


Mechanical Ventilation After Bidirectional Superior Cavopulmonary Anastomosis for Single-Ventricle Physiology: A Comparison of Pressure Support Ventilation and Neurally Adjusted Ventilatory Assist.
We evaluated the effects of different respiratory assist modes on cerebral blood flow (CBF) and arterial oxygenation in single-ventricle patients after bidirectional superior cavopulmonary anastomosis (BCPA). We hypothesized that preserved auto-regulation of respiration during neurally adjusted ventilatory assist (NAVA) may have potential advantages for CBF and pulmonary blood flow regulation after the BCPA procedure. We enrolled 23 patients scheduled for BCPA, who underwent pressure-controlled ventilation (PCV), pressure support ventilation (PSV), and NAVA at two assist levels for all modes in a randomized order. PCV targeting large V T (15 mL × kg(-1)) resulted in lower CBF and oxygenation compared to targeting low V T (10 mL × kg(-1)). During PSV and NAVA, ventilation assist levels were titrated to reduce EAdi from baseline by 75 % (high assist) and 50 % (low assist). High assist levels during PSV (PSVhigh) were associated with lower PaCO2, PaO2, and O2SAT, lower CBF, and higher pulsatility index compared with those during NAVAhigh. There were no differences in parameters when using low assist levels, except for slightly greater oxygenation in the NAVAlow group. Modifying assist levels during NAVA did not influence hemodynamics, cerebral perfusion, or gas exchange. Targeting the larger V T during PCV resulted in hyperventilation, did not improve oxygenation, and was accompanied by reduced CBF. Similarly, high assist levels during PSV led to mild hyperventilation, resulting in reduced CBF. NAVA's results were independent of the assist level chosen, causing normalized PaCO2, improved oxygenation, and better CBF than did any other mode, with the exception of PSV at low assist levels.


Fibromyxoma of the axis.
Fibromyxoma of bone is a rare benign tumor of fibrous tissue origin. The typical location is the jaws. Sporadic extragnathic cases have been reported, but fibromyxoma of the spine has not been reported. The histological appearance of fibromyxoma is benign and includes abundant extracellular fibrous and myxoid stroma with varying amounts of calcification and ossification. Myxoid changes are usually extensive. Extragnathic fibromyxoma of bone should be distinguished from benign cartilage-forming bone tumors, such as chondromyxoid and myxoid chondrosarcoma and myxoma of bone. It has also been suggested that fibromyxoma is a variant of myxoid fibrous dysplasia, whereas other authors reported extragnathic fibromyxoma resulting from myxoid degeneration of bone tumors, such as chondrosarcoma or fibrosarcoma. The overtreatment of patients with fibromyxoma of bone due to an aggressive imaging appearance should be avoided; the prognosis is excellent compared with the jaw variant and depends on the location and extent of the tumor. This article describes a case of a 21-year-old woman with fibromyxoma of bone originating from the spinous process of the axis. Clinical examination showed a tender mass in the midline of the posterior aspect the neck and slight limitation of neck range of motion; neurologic examination was normal. Diagnosis was obtained with a preoperative biopsy. Marginal excision of the lesion with posterior laminectomy of the axis was performed. The facets were preserved, and no fusion was performed. At last follow-up 2 years after diagnosis and treatment, the patient was asymptomatic with no evidence of local recurrence.


In-phase supermode selection in ring-type and concentric-type multicore fibers using large-mode-area single-mode fiber.
We propose an all-fiber-optic supermode selection scheme based on large-mode-area single-mode fiber for multicore fiber (MCF). The supermode selection in terms of the coupling coefficient is investigated and compared for various ring-type and concentric-type MCFs. The in-phase supermode is found to have a significantly higher coupling coefficient than other supermodes--demonstrating significant and desirable supermode selection characteristics. This scheme has shown better in-phase supermode selection performance than the conventional free-space Talbot cavity. It is found to be effective in selecting the in-phase supermode for both ring-type and concentric-type MCFs and promising for all-fiber MCF lasers with high power output and good beam quality.


Nocturnal hypoglycaemia in patients receiving conventional treatment with insulin.
The prevalence of nocturnal biochemical hypoglycaemia--that is, blood glucose concentrations below 3 mmol/l (55 mg/100 ml)--was evaluated in a random sample of 58 insulin dependent diabetics receiving twice daily insulin. Seventeen patients had at least one blood glucose value below 3 mmol/l (55 mg/100 ml) and five a value below 2 mmol/l (36 mg/100 ml) during the night. Both bedtime (2300) and fasting morning (0700) blood glucose concentrations were significantly lower in the group with nocturnal hypoglycaemia compared with the group without (p less than 0.00001). If the bedtime blood glucose concentration was below 6 mmol/l (108 mg/100 ml) the risk of nocturnal hypoglycaemia was 80% (95% confidence limits 51-96%). If the bedtime blood glucose concentration was above 6 mmol/l the likelihood of hypoglycaemia not occurring during the night was 88% (74-96%). The mean glycosylated haemoglobin A1c (HbA1c) concentration in the group with nocturnal biochemical hypoglycaemia (8.2 (range 5.0-12.4)%) was significantly lower than that in the group without (9.4(7.0-14.2)%) (p less than 0.02). The prevalence of nocturnal hypoglycaemia in the patients receiving twice daily insulin (29%) was compared with that in 15 patients receiving thrice daily insulin (47%) and was not found to be significantly different. The likelihood of this risk being greater with thrice daily insulin was, however, 88%. No patient with nocturnal biochemical hypoglycaemia woke up during the night with symptomatic hypoglycaemia. Nocturnal biochemical hypoglycaemia is common during twice daily treatment with insulin, and low values of HbA1c might be associated with a higher risk of such hypoglycaemia. The blood glucose concentration at bedtime is a significant predictor of nocturnal biochemical hypoglycaemia, and HbA1c values might be of help in identifying patients at risk.


Ex vivo pretreatment with melatonin improves survival, proangiogenic/mitogenic activity, and efficiency of mesenchymal stem cells injected into ischemic kidney.
Bone marrow mesenchymal stem cells (MSCs) have shown great potential in cell therapy of solid organs. Approaches to improving the ability of grafted MSCs to survive and secrete paracrine factors represent one of the challenges for the further development of this novel therapy. In the present study, we designed a strategy of ex vivo pretreatment with the pineal hormone melatonin to improve survival, paracrine activity, and efficiency of MSCs. Using a rat model of acute renal failure, we showed that melatonin pretreatment strongly increased survival of MSCs after intraparenchymal injection. This effect was concomitant with overstimulation of angiogenesis, proliferation of renal cells, and accelerated recovery of renal function. To gain insight into the mechanisms involved in the effects observed in vivo, melatonin was tested in vitro on cultured MSCs. Our results show that through stimulation of specific melatonin receptors, melatonin induced an overexpression of the antioxidant enzyme catalase and superoxide dismutase-1 and increased the resistance of MSCs to hydrogen peroxide-dependent apoptosis. Compared with untreated cells, MSCs incubated with melatonin displayed a higher expression of basic fibroblast growth factor and hepatocyte growth factor. In addition, conditioned culture media from melatonin-treated MSCs stimulated tube formation by endothelial progenitor cells and proliferation of proximal tubule cells in culture. In conclusion, our results show that melatonin behaves as a preconditioning agent increasing survival, paracrine activity, and efficiency of MSCs. The use of this molecule for pretreatment of stem cells may represent a novel and safe approach to improving the beneficial effects of cell therapy of solid organs.


Large-scale determination of sequence, structure, and function relationships in cytosolic glutathione transferases across the biosphere.
The cytosolic glutathione transferase (cytGST) superfamily comprises more than 13,000 nonredundant sequences found throughout the biosphere. Their key roles in metabolism and defense against oxidative damage have led to thousands of studies over several decades. Despite this attention, little is known about the physiological reactions they catalyze and most of the substrates used to assay cytGSTs are synthetic compounds. A deeper understanding of relationships across the superfamily could provide new clues about their functions. To establish a foundation for expanded classification of cytGSTs, we generated similarity-based subgroupings for the entire superfamily. Using the resulting sequence similarity networks, we chose targets that broadly covered unknown functions and report here experimental results confirming GST-like activity for 82 of them, along with 37 new 3D structures determined for 27 targets. These new data, along with experimentally known GST reactions and structures reported in the literature, were painted onto the networks to generate a global view of their sequence-structure-function relationships. The results show how proteins of both known and unknown function relate to each other across the entire superfamily and reveal that the great majority of cytGSTs have not been experimentally characterized or annotated by canonical class. A mapping of taxonomic classes across the superfamily indicates that many taxa are represented in each subgroup and highlights challenges for classification of superfamily sequences into functionally relevant classes. Experimental determination of disulfide bond reductase activity in many diverse subgroups illustrate a theme common for many reaction types. Finally, sequence comparison between an enzyme that catalyzes a reductive dechlorination reaction relevant to bioremediation efforts with some of its closest homologs reveals differences among them likely to be associated with evolution of this unusual reaction. Interactive versions of the networks, associated with functional and other types of information, can be downloaded from the Structure-Function Linkage Database (SFLD; http://sfld.rbvi.ucsf.edu).


Surround-Masking Affects Visual Estimation Ability.
Visual estimation of numerosity involves the discrimination of magnitude between two distributions or perceptual sets that vary in number of elements. How performance on such estimation depends on peripheral sensory stimulation is unclear, even in typically developing adults. Here, we varied the central and surround contrast of stimuli that comprised a visual estimation task in order to determine whether mechanisms involved with the removal of unessential visual input functionally contributes toward number acuity. The visual estimation judgments of typically developed adults were significantly impaired for high but not low contrast surround stimulus conditions. The center and surround contrasts of the stimuli also differentially affected the accuracy of numerosity estimation depending on whether fewer or more dots were presented. Remarkably, observers demonstrated the highest mean percentage accuracy across stimulus conditions in the discrimination of more elements when the surround contrast was low and the background luminance of the central region containing the elements was dark (black center). Conversely, accuracy was severely impaired during the discrimination of fewer elements when the surround contrast was high and the background luminance of the central region was mid level (gray center). These findings suggest that estimation ability is functionally related to the quality of low-order filtration of unessential visual information. These surround masking results may help understanding of the poor visual estimation ability commonly observed in developmental dyscalculia.


Young people and mental health: novel methods for systematic review of research on barriers and facilitators.
This paper describes how barriers to, and facilitators of, good mental health amongst young people (11-21 years) were elucidated from a systematic review of studies of young people's views and how these barriers and facilitators were compared with effectiveness studies to identify effective and appropriate interventions, promising interventions needing further evaluation and the need for further intervention. All studies were published before 2000. No clear pattern for effectiveness emerged in terms of mental health promotion focus, the type of intervention, intervention provider or young people. Well-evaluated interventions neither always target what we know young people themselves see as important barriers to their mental health (for instance, loss of friends and family, violence and bullying) nor always build on what they see as key facilitators, particularly their preferred coping strategies. In particular, while young people see material and physical resources as major influences on their mental health, few evaluated interventions targeted these. Rigorously evaluated interventions more often addressed priorities not raised by young people themselves and populations at low risk for mental health problems. These innovative review methods can inform intervention development and evaluation in a new way based on the strengths and needs identified by the target population.


Identifying cervical infection among pregnant women in Nairobi, Kenya: limitations of risk assessment and symptom-based approaches.
To examine characteristics of pregnant women associated with cervical infection, and to evaluate the accuracy of symptom-based and risk assessment systems which have been developed for identifying cervical infection in antenatal women. Interviews were conducted and physical examinations performed on 291 consecutive antenatal clinic attenders in nairobi, Kenya. Vaginal, cervical, urine and blood specimens were also obtained for analysis. The following disease prevalences were observed: candidiasis 26.2%; trichomoniasis 19.9%; bacterial vaginosis 20.6%; any vaginal infection 53.8%; chlamydial cervicitis (CT) 8.8%; gonococcal cervicitis (GC) 2.4%; any cervical infection 10.8%. The only statistically significant association with GC and/or CT cervical infection was the presence of cervical friability (OR = 2.1, P = 0.05). There were trends towards associations with the presence of endocervical mucopus (OR = 2.6, P = 0.06), reporting a new sex partner in the past 3 months (OR = 2.2, P = 0.16) and reporting that a sex partner had an STD-related symptom (OR = 4.4, P = 0.13). There were no associations with other demographic, behavioural or medical characteristics. Risk scores previously developed for detecting GC/CT cervicitis in developing country antenatal populations generally performed poorly. The prevalences of vaginal and cervical infection observed were extremely high among these "low risk" women. Owing probably to high levels of vaginal infection and to behavioural characteristics of this urban population, factors which elsewhere have been associated with cervical infection were not found to be so in this setting. Further work on symptom-based approaches and risk assessment for STD case detection in pregnant women is required before STD management recommendations can be generalised.


When will a pulsar in supernova 1987a be seen?
The means by which a pulsar might be detected in the remnant of supernova 1987a in the Large Magelanic Cloud is examined. One possibility is that the slower-than-radioactive decay typically seen in the type II light curves is itself the sign of powering by the underlying pulsar, with the decline representing not the spinning down of the pulsar but rather the declining nebular opacity that would allow increasing amounts of the energy to escape as gamma rays. The test of this hypothesis (if the supernova conforms to type II expectations) would be to look for the "missing" energy in the form of those gamma rays that escape from the remnant instead of powering it.


S100A2: A potential biomarker to differentiate malignant from tuberculous pleural effusion.
S100 calcium binding protein A2 (S100A2)-which has been testified to have an abnormal expression in non-small cell lung cancer (NSCLC)-is considered as an effective biomarker in the diagnosis and prognosis of this malignancy. In this study, we detected the S100A2 levels in pleural effusion, aiming to evaluate its potential value in differentiating malignant pleural effusion (MPE) from tuberculous pleural effusion (TPE). We collected pleural effusion from 104 NSCLC patients with MPE and 96 tubercular pleurisy cases. Enzyme-linked immunosorbent assay (ELISA) was performed to measure the levels of S100A2 in these samples. Meanwhile, the serum S100A2 levels were also examined in same subjects. The data concerning the expression of those commonly-used markers, including CEA, CYFRA211 and NSE, were obtained from medical records. Like other classified biomarkers, S100A2 had an over-expression in both pleural effusion and sera of the NSCLC patients compared with controls (P = 0.000), though having a lower P value. Receiver operating characteristic (ROC) analysis showed that the levels of S100A2 in pleural effusion (PE) could distinguish MPE from tuberculous pleurisy (Area Under the Receiver Operating Characteristic Curve (AUC) = 0.887), and its diagnostic value in hydrothorax was obviously higher than in serum (AUC = 0.709). Our results indicate that levels of S100A2 are significantly elevated in MPE, and that S100A2 may serve as a diagnostic biomarker for NSCLC patients with MPE. In further studies, we will validate our findings with a larger sample population.


High prevalence of anterior pituitary deficiencies after cranial radiation therapy for skull base meningiomas.
Cranial irradiation represents one of the first line treatment proposed in skull base meningiomas. While cranial irradiation is associated with a high risk of secondary hypopituitarism, few studies focused on the specific location of skull base meningiomas. Fifty-two adults receiving photon-beam therapy for skull base meningiomas between 2003 and 2014 in our Institution were included. Anterior pituitary (ACTH, FSH, GH, LH, TSH and prolactin) as well as corresponding peripheral hormones (8 am-Cortisol, IGF-1, fT3, fT4, 17βestradiol or testosterone) were biologically screened before radiotherapy (baseline), then yearly until March 2019. The pituitary gland (PG) was delineated on CT and the mean dose delivered to it was calculated. Mean age at diagnosis was 56 +/- 14 years. Median follow-up was 7 years. Up to 60% of patients developed at least ≥2 pituitary deficiencies, 10 years after radiotherapy. Gonadotroph, thyrotroph, corticotroph and somatotroph deficiencies occurred in 37, 28, 18 and 15% of patients, respectively. Hyperprolactinemia was found in 13% of patients. None patient had only one pituitary deficiency. In the multivariate analysis, a delivered dose to the PG ≥ 50 Gy or a meningioma size ≥40 mm significantly increased the risk of developing hypopituitarism. Over a long-term follow-up, cranial radiation therapy used in skull base meningiomas led to a high prevalence of hypopituitarism, further pronounced in case of tumor ≥4 cm. These results advocate for an annual and prolonged follow-up of the pituitary functions in patients with irradiated skull base meningiomas.


Stratum corneum pH in atopic dermatitis: impact on skin barrier function and colonization with Staphylococcus Aureus.
Recent studies have provided new insights into the occurrence, causes, and pathogenetic consequences of changes in the skin pH in atopic dermatitis, particularly with respect to skin barrier function and colonization with Staphylococcus aureus. Growing evidence suggests an impaired release of proton donors, such as amino acids, urocanic acid, and lactic acid, to the stratum corneum in atopic dermatitis, as a result of reductions in filaggrin proteolysis and sweat secretion. In addition, an impaired formation of free fatty acids from sebaceous lipids and epidermal phospholipids seems to be involved. Because both lipid organization and lipid metabolism in the stratum corneum requires an acidic pH, these alterations might contribute to the disturbance of skin barrier function observed in atopic dermatitis. Furthermore, bacterial growth and virulence of S. aureus, as well as defensive host mechanisms, have increasingly been delineated as pH dependent, giving rise to a new understanding of the pathophysiology underlying increased skin colonization seen in atopic dermatitis.


Cystinosis: a review.
Cystinosis is the most common hereditary cause of renal Fanconi syndrome in children. It is an autosomal recessive lysosomal storage disorder caused by mutations in the CTNS gene encoding for the carrier protein cystinosin, transporting cystine out of the lysosomal compartment. Defective cystinosin function leads to intra-lysosomal cystine accumulation in all body cells and organs. The kidneys are initially affected during the first year of life through proximal tubular damage followed by progressive glomerular damage and end stage renal failure during mid-childhood if not treated. Other affected organs include eyes, thyroid, pancreas, gonads, muscles and CNS. Leucocyte cystine assay is the cornerstone for both diagnosis and therapeutic monitoring of the disease. Several lines of treatment are available for cystinosis including the cystine depleting agent cysteamine, renal replacement therapy, hormonal therapy and others; however, no curative treatment is yet available. In the current review we will discuss the most important clinical features of the disease, advantages and disadvantages of the current diagnostic and therapeutic options and the main topics of future research in cystinosis.


A prospective trial of GreenLight PVP (HPS120) versus transurethral resection of the prostate in the treatment of lower urinary tract symptoms in Ontario, Canada.
Photoselective vaporization of the prostate (PVP) is a bloodless, relatively painless alternative to transurethral resection of the prostate (TURP) for relief of lower urinary tract symptoms (LUTS) in benign prostatic hyperplasia (BPH). We compare the effectiveness, safety and cost-effectiveness of Greenlight Laser PVP (HPS-120) and TURP. We conducted a prospective, non-randomized trial in 3 Ontario centres from March 2008 to February 2011. Assessments were completed at baseline, 1 and 6 months following surgery at the physicians' offices and at 12 and 24 months by phone. The primary outcome was the change in International Prostate Symptoms Score (IPSS) score at 6 months versus baseline. Secondary outcomes were changes in flow rate, postvoid residual (PVR), prostate-specific antigen (PSA) and sexual health inventory for men (SHIM) scores. Adverse events, health-related quality of life (HRQoL), resource utilization and productivity losses were collected. Although the IPSS decreased in both arms (n = 140 for PVP and n = 24 for TURP) between baseline and 6 months, the difference in change over time between the groups was not statistically significant (p = 0.718). Other outcomes improved equally from baseline and 6 months (Qmax, SHIM, PSA and HRQoL), with only changes in PVR favouring PVP (p = 0.018). There were no statistical differences in serious adverse events. In total, 130 of 140 PVP patients were outpatients, all TURP subjects were inpatients. PVP was less costly than TURP ($3891 vs. $4863; p < 0.001) with similar quality-adjusted life years (0.448 vs. 0.441; p = 0.658). Greenlight Laser PVP (HPS-120) is a safe and cost-effective alternative to TURP for outpatient treatment of LUTS and can be completed as an outpatient with minimal blood loss.


Holistic Management of Schizophrenia Symptoms Using Pharmacological and Non-pharmacological Treatment.
Individuals with schizophrenia lead a poor quality of life, due to poor medical attention, homelessness, unemployment, financial constraints, lack of education, and poor social skills. Thus, a review of factors associated with the holistic management of schizophrenia is of paramount importance. The objective of this review is to improve the quality of life of individuals with schizophrenia, by addressing the factors related to the needs of the patients and present them in a unified manner. Although medications play a role, other factors that lead to a successful holistic management of schizophrenia include addressing the following: financial management, independent community living, independent living skill, relationship, friendship, entertainment, regular exercise for weight gained due to medication administration, co-morbid health issues, and day-care programmes for independent living. This review discusses the relationship between different symptoms and problems individuals with schizophrenia face (e.g., homelessness and unemployment), and how these can be managed using pharmacological and non-pharmacological methods. Thus, the target of this review is the carers of individuals with schizophrenia, public health managers, counselors, case workers, psychiatrists, and clinical psychologists aiming to enhance the quality of life of individuals with schizophrenia.


Modulation of protein phosphatase 2A activity alters androgen-independent growth of prostate cancer cells: therapeutic implications.
Earlier we identified PPP2CA, which encodes for the α-isoform of protein phosphatase 2A (PP2A) catalytic subunit, as one of the downregulated genes in androgen-independent prostate cancer. PP2A is a serine/threonine phosphatase and a potent tumor suppressor involved in broad cellular functions; however, its role in prostate cancer has not yet been determined. Here, we have investigated the effect of PP2A activity modulation on the androgen-independent growth of prostate cancer cells. Our data show that the PPP2CA expression and PP2A activity is downregulated in androgen-independent (C4-2) prostate cancer cells as compared with androgen-dependent (LNCaP) cells. Downregulation of PP2A activity by pharmacologic inhibition or short interfering RNA-mediated PPP2CA silencing sustains the growth of LNCaP cells under an androgen-deprived condition by relieving the androgen deprivation-induced cell-cycle arrest and preventing apoptosis. Immunoblot analyses reveal enhanced phosphorylation of Akt, extracellular signal-regulated kinase (ERK), BAD, increased expression of cyclins (A1/D1), and decreased expression of cyclin inhibitor (p27) on PP2A downregulation. Furthermore, our data show that androgen receptor (AR) signaling is partially maintained in PP2A-inhibited cells through increased AR expression and ligand-independent phosphorylation. Pharmacologic inhibition of Akt, ERK, and AR suggest a role of these signaling pathways in facilitating the androgen-independent growth of LNCaP cells. These observations are supported by the effect of ceramide, a PP2A activator, on androgen-independent C4-2 cells. Ceramide inhibited the growth of C4-2 cells on androgen deprivation, an effect that could be abrogated by PP2A downregulation. Altogether, our findings suggest that modulation of PP2A activity may represent an alternative therapeutic approach for the treatment of advanced androgen-independent prostate cancer.


Differential miRNA expression profiles in proliferating or differentiated keratinocytes in response to gamma irradiation.
MicroRNAs (miRNAs), a group of short non-coding RNAs that negatively regulate gene expression, have recently emerged as potential modulators of cellular response to ionizing radiations both in vitro and in vivo in various cell types and tissues. However, in epidermal cells, the involvement of the miRNA machinery in the cellular response to ionizing radiations remains to be clarified. Indeed, understanding the mechanisms of cutaneous radiosensitivity is an important issue since skin is the most exposed organ to ionizing radiations and among the most sensitive. We settled up an expression study of miRNAs in primary human skin keratinocytes using a microfluidic system of qPCR assay, which permits to assess the expression of almost 700 annotated miRNAs. The keratinocytes were cultured to a proliferative or a differentiated state mimicking basal or suprabasal layers of human epidermis. These cells were irradiated at 10 mGy or 6 Gy and RNA was extracted 3 hours after irradiation. We found that proliferative cells irradiated at 6 Gy display a global fall of miRNA expression whereas differentiated cells exposed to the same dose display a global increase of miRNAs expression. We identified twenty miRNAs weakly but significantly modulated after 6 Gy irradiation, whereas only 2 miRNAs were modulated after low-dose irradiation in proliferating cells. To go further into the biological meaning of this miRNA response, we over-expressed some of the responding miRNA in proliferating cells: we observed a significant decrease of cell viability 72 hours after irradiation. Functional annotation of their predicted targets revealed that G-protein related pathways might be regulated by these responding miRNAs. Our results reveal that human primary keratinocytes exposed to ionizing irradiation expressed a miRNA pattern strongly related to the differentiation status of irradiated cells. We also demonstrate that some miRNAs play a role in the radiation response to ensure the short-term survival of irradiated keratinocytes.


The importance of resilience and stress to maintaining smoking abstinence and cessation: a qualitative study in Australia with people diagnosed with depression.
This study explored stress in relation to smoking and how non-smokers (never-smoked and ex-smokers) are 'resilient' to smoking in a population where there is a high prevalence of smoking (people diagnosed with depression). In-depth oral history interviews were conducted with 34 adult participants from metropolitan Adelaide, and who were medically diagnosed with depression. Participants were recruited according to their smoking status (currently smoking, ex-smoker, and never-smoked). Smoking was taken-up and maintained for a number of reasons that included perceived high levels of stress. Resilience to stress in relation to smoking was also a major theme. Non-smoking participants tended to be more resilient to stress. Ex-smokers were able to quit for a number of varied reasons during critical transition points in their lives. The never-smoked participants reported successful strategies to cope with stress but not all of them were necessarily healthy. There was often interplay between external factors and the individual's internal properties that led to a building or an erosion of resilience. Smokers and ex-smokers have indicated a strong relationship between stress and tobacco use. Ex-smokers and the never-smoked participants have demonstrated how being 'resilient' to stress can be important to smoking abstinence. The finding that external factors can interact with internal properties to build resilience in relation to stress and smoking is important for policy and practice.


Lack of adverse clopidogrel-atorvastatin clinical interaction from secondary analysis of a randomized, placebo-controlled clopidogrel trial.
Statins primarily metabolized by cytochrome P450 3A4 (CYP3A4) reportedly reduce clopidogrel's metabolism to active metabolite, thus attenuating its inhibition of platelet aggregation ex vivo. However, the clinical impact of this interaction has not been evaluated. Clopidogrel for the Reduction of Events During Observation (CREDO) was a double-blind, placebo-controlled, randomized trial comparing pretreatment (300 mg) and 1-year (75 mg/d) clopidogrel therapy (clopidogrel) with no pretreatment and 1-month clopidogrel therapy (75 mg/d) (control) after a planned percutaneous coronary intervention. All patients received aspirin. The 1-year primary end point was a composite of death, myocardial infarction, and stroke. We performed a post hoc analysis to evaluate the clinical efficacy of concomitant clopidogrel and statin administration, categorizing baseline statin use to those predominantly CYP3A4-metabolized (atorvastatin, lovastatin, simvastatin, and cerivastatin) (CYP3A4-MET) or others (pravastatin and fluvastatin) (non-CYP3A4-MET). Of the 2116 patients enrolled, 1001 received a CYP3A4-MET and 158 a non-CYP3A4-MET statin. For the overall study population, the primary end point was significantly reduced in the clopidogrel group (8.5% versus 11.5%, RRR 26.9%; P=0.025). This clopidogrel benefit was similar with statin use, irrespective of treatment with a CYP3A4-MET (7.6% clopidogrel, 11.8% control, RRR 36.4%, 95% CI 3.9 to 57.9; P=0.03) or non-CYP3A4-MET statin (5.4% clopidogrel, 13.6% control, RRR 60.6%, 95% CI -23.9 to 87.4; P=0.11). Patients given atorvastatin or pravastatin had similar 1-year event rates. Additionally, concomitant therapy with statins had no impact on major or minor bleeding rates. Although ex vivo testing has suggested a potential negative interaction when coadministering a CYP3A4-metabolized statin with clopidogrel, this was not clinically observed statistically in a post hoc analysis of a placebo-controlled study.


Joint effects of natural selection and recombination on gene flow between Drosophila ananassae populations.
We estimated DNA sequence variation in a 5.7-kb fragment of the furrowed (fw) gene region within and between four populations of Drosophila ananassae; fw is located in a chromosomal region of very low recombination. We analyzed gene flow between these four populations along a latitudinal transect on the Indian subcontinent: two populations from southern, subtropical areas (Hyderabad, India, and Sri Lanka) and two from more temperate zones in the north (Nepal and Burma). Furthermore, we compared the pattern of differentiation at fw with published data from Om(1D), a gene located in a region of normal recombination. While differentiation at Om(1D) shows an isolation-by-distance effect, at fw the pattern of differentiation is quite different such that the frequencies of single nucleotide polymorphisms are homogenized over extended geographic regions (i.e., among the two populations of the northern species range from Burma and Nepal as well as among the two southern populations from India and Sri Lanka), but strongly differentiated between the northern and southern populations. To examine these differences in the patterns of variation and differentiation between the Om(1D) and fw gene regions, we determine the critical values of our previously proposed test of the background selection hypothesis (henceforth called F(ST) test). Using these results, we show that the pattern of differentiation at fw may be inconsistent with the background selection model. The data depart from this model in a direction that is compatible with the occurrence of recent selective sweeps in the northern as well as southern populations.


Emergency contraception: are pediatric residents counseling and prescribing to teens?
(1) To assess pediatric residents' attitudes and practices related to counseling about and prescribing emergency contraceptive pills (ECPs) for teens. (2) To determine whether attitudes, counseling, and prescribing practices vary among different levels of residency training. Questionnaire. Two large inner-city academic medical centers in New York City. Pediatric residents (PGY 1-3). Attitudes, counseling and prescribing patterns of ECPs by the pediatric residents 101/120 residents participated in the survey; 35% PGY1, 38% PGY2, 28% PGY3. Less than a third (26%) reported counseling teens about the availability of ECPs during routine non-acute care visits and just over half (56%) provided ECP counseling during visits for contraception. Only 6% of pediatric residents reported that they prescribed ECPs often, while 42% never prescribed ECPs. The majority of the residents did not think that prescribing ECPs would encourage teens to practice unsafe sex or would discourage compliance with other contraceptive methods (70% and 68%, respectively). However, the majority (67%) also reported that they did not think that ECPs should be available over the counter, without prescription. Further analysis by year of training showed that more junior and senior residents than interns counseled adolescents about ECPs at both routine health care maintenance visits and at visits for contraception (32% vs 15%; 62% vs 42%, respectively), would provide adolescent girls with ECPs to have on hand prior to an episode of unprotected sex (52% vs 31%), and thought that ECPs should be available over the counter (39% vs 20%), P < 0.05. Pediatric residents are missing opportunities to prevent unintended teenage pregnancy but they become more likely to counsel about and prescribe ECPs as they progress through residency training.


Gene therapy of cancer - 12th International Conference.
The 12th International Conference on Gene Therapy of Cancer, sponsored by the Sidney Kimmel Cancer Center, was organized by Robert E Sobol and Kevin Scanlon, and centered on the development and use of viral vectors as therapeutics. The emphasis of this report is on translational and clinical studies, primarily focused on delivery strategies rather then tumor antigens. In many instances, transduced/transfected cells were used to deliver the transgene, including not only dendritic cells as professional antigen-presenting cells, but also transfected autologous and allogenic tumor cells. In addition, immune augmentation with cytokines and growth factor transgenes, including the recently cloned proteins IL-23 and IL-24, were discussed, as was the use of antisense to TGFbeta2 to overcome tumor-associated immunosuppression. The majority of speakers discussed strategies using viral vectors, although strategies with electroporation, minimalistic immunogenically defined gene expression vectors and plasmids were also mentioned. Adenoviruses were the predominating viral vector, although pox viral, herpes simplex viral, retroviral and lentiviral vectors were also used.


SEROVARS AND ANTIMICROBIAL RESISTANCE OF Salmonella spp. ISOLATED FROM TURKEY AND BROILER CARCASSES IN SOUTHERN BRAZIL BETWEEN 2004 AND 2006.
Salmonella spp. causes diseases in fowls, when species-specific serovars (Salmonella Pullorum and S.Gallinarum) are present in flocks, and public health problems, when non-typhoid serovars are isolated, as well as possible bacterial resistance induced by the preventive and therapeutic use of antimicrobials in animal production. This study describes the serovars and bacterial resistance of 280 Salmonella spp. strains isolated from turkey and broiler carcasses in Southern Brazil between 2004 and 2006. Salmonella Enteritidis was the most prevalent serovar (55.7%), followed by Heidelberg (5.0%), Agona (4.3%), Bredeney (3.9%), Hadar (3.2%), and Typhimurium (2.9%). Tennessee and S. Enterica subspecies enterica(O: 4.5) were isolated only in turkeys, and Hadar (18.6%) was the most prevalent serovar in this species. Antimicrobial susceptibility tests were performed in 178 isolates (43 from turkeys and 135 from broilers). All isolates were sensitive to amoxicillin + clavulanic acid, polymyxin B, ciprofloxacin, and norfloxacin, and were resistant to bacitracin and penicillin. Broiler carcass isolates showed resistance to nalidixic acid (48.9%), nitrofurantoin (34.3%), neomycin (9.6%), tetracycline (5.2%), and kanamycin (8.9%); and turkey carcass isolates were resistant to nalidixic acid (62.8%), tetracycline (34.9%), and neomycin (30.2%), with a significant difference in turkeys when compared to broiler carcass isolates. These results indicate the need for judicious use of antimicrobials in livestock production, given that the serovars identified are potential causes of food poisoning.


Transesophageal echocardiography and computerized tomography angiography mismatch in left atrial appendage thrombus evaluation.
Transesophageal echocardiography (TEE) is the gold standard test for the diagnosis of left atrial appendage (LAA) thrombus. Nonetheless, computerized tomography angiography (CTA) is readily used to exclude LAA thrombus before pulmonary vein isolation (PVI) and LAA closure procedures. We aimed to assess the comparability of LAA thrombus diagnosis using chest CTA scans in patients with atrial fibrillation who underwent TEE. Retrospective collection of consecutive patients with atrial fibrillation who underwent TEE and chest CTA within 30 days and had evidence of spontaneous echo contrast (SEC) or LAA thrombus on TEE. Clinical, demographic, and echo data were collected. Prospective analysis of the CTA for evidence of LAA thrombus in the same group of patients was performed. We compared the findings of the two modalities. Out of 1550 patients with atrial fibrillation who underwent TEE examinations in the study period, 63 patients underwent TEE within 30 days of a chest CTA scan. Twenty-three patients had LAA thrombus and 40 had some degree of SEC according to TEE. On CTA, 11 were interpreted as positive with a high level of suspicion for the presence of an LAA thrombus. Six patients (26.1%) had LAA thrombus according to both CT and TEE. Therefore, low concordance was found between test results (chi-squared continuity correction = 5.5, df = 1, and P -value = 0.01902). The discrepancy between CTA and TEE results suggests these examinations might be more suitable as complementary examinations to exclude LAA thrombus.


Analysis of the biochemical properties of, and complex formation between, glycoproteins H and L of the gamma2 herpesvirus bovine herpesvirus-4.
Genes encoding glycoprotein gH and gL homologues were localized in the genome of the gamma-herpesvirus bovine herpesvirus-4 (BHV-4). Both genes were sequenced and glutathione S-transferase fusion proteins were produced and used to immunize rabbits against the translation products of the two genes. The anti-gH serum recognized a protein with an apparent molecular mass (MM) of 110 kDa both in infected cells and in virions. This protein was sensitive to endo-beta-N-acetylglucosaminase-H (endoH) and endoglycosidase F-N-glycosidase F (endoF-PNGaseF) digestion. A protein with the same relative mobility was immunoprecipitated from infected cells radiolabelled with [3H]glucosamine which confirmed that this product (gp110), now designated BHV-4 gH, was glycosylated. Western blotting with the anti-gL serum detected in infected cells a product with an apparent MM ranging from 31-35 kDa and diffusely migrating protein species ranging from 45-65 kDa. Tunicamycin, monensin, endoH or endoF-PNGaseF treatments showed that both the 31-35 kDa and the 45-65 kDa proteins were glycosylated, gp31-35 being a precursor of the 45-65 kDa glycoprotein species. In radioimmunoprecipitation assays, the anti-gL serum immunoprecipitated from infected cells two glycosylated proteins with apparent MMs of 31-35 kDa (gp31-35) and 45-55 kDa (gp45-55). However a third glycoprotein, gp110, was also immunoprecipitated together with gp31-35 and gp45-55. gp110 and gp45-55 were subsequently confirmed to be virion glycoproteins corresponding to mature forms of BHV-4 gH and gL respectively. In addition, the present study clearly demonstrated complex formation between BHV-4 gH and gL both in virions and in infected cells.