Active skeletal muscle metabolism and tension production: the influence of biopsies.
The influence of repeated sampling by the biopsy technique on skeletal muscle's metabolic and force-output responses was studied using the in situ canine gastrocnemius preparation. The left muscle was stimulated (8 V, 0.2 ms) for 1 h at 3 Hz. In the biopsy series (n = 9) muscle samples were taken at rest, and at 0.5, 2, 5, 15, 30, 45, and 60 min of stimulation. In the control series (n = 8) the left and right muscles were quick-frozen in N2 immediately after the 60 min of stimulation. The two series were not different in blood flow, VO2, arterial or venous [H+], muscle glycogen, or lactate release throughout the 60 min of activity. The lactate release was transient and was associated with an accumulation of intramuscular lactate and a period of rapid glycogenolysis. The biopsy series had a modest but significantly (p < 0.05) higher muscle lactate concentration both at rest and at the end of the contractions. The biopsy series also had less (p < 0.05) tension development throughout the hour; however, the O2 cost per unit of tension development was not different between groups, nor was the rate of tension decline over time different. This together with the similarities in perfusion, carbohydrate use, and lactate metabolism suggests that repeated biopsies had minimal impact on the muscle. The technique allows the collection of data over time; this improves the detail of experiments and means that fewer animals are required for a study.


Helicobacter pylori prevalence and clinical significance in patients with quiescent Crohn's disease.
Helicobacter pylori (HP) infection is present in about 50% of the global population, and is associated with chronic gastritis, peptic disease and gastric malignancies. HP prevalence in Crohn's disease (CD) patients was shown to be low compared to the general population, and its influence on disease activity is yet to be determined. Our aims were to determine the prevalence of HP in a selected group of CD patients with quiescent disease, and to assess the influence of its eradication on disease activity and endoscopic and laboratory activity measures. Consecutive CD patients with quiescent disease underwent meticulous disease evaluation with MR enterography (MRE), video capsule endoscopy (VCE), CRP, fecal calprotectin and CDAI. All patients were tested for the presence of HP using stool antigen detection kit. Patients infected with HP were offered eradication treatment with sequential therapy. HP eradication was confirmed using urease breath test and stool antigen test. The influence of HP eradication on disease activity was assessed. Out of 56 patients enrolled, six patients (10.7%) had HP infection. Of them, five patients had gastro- duodenitis per VCE. All HP positive patients were offered eradication treatment and underwent successful eradication. Notably, 23 (50%) of patients had proximal disease per VCE, most of them (78%) were HP negative. CDAI, CRP, fecal calprotectin and VCE Lewis inflammatory score did not change significantly following HP eradication, Gastric findings on VCE were not impacted by HP eradication. The prevalence of HP infection in patients with quiescent CD is relatively low. Eradication of the bacteria did not significantly change neither disease activity measures nor the presence of gastro- duodenitis per VCE, suggesting it might be part of proximal CD. The influence of HP on CD activity merits further investigation.


College Students' Sexual Consent Communication And Perceptions of Sexual Double Standards: A Qualitative Investigation.
Affirmative consent standards adopted by colleges and universities are meant to decrease miscommunication that may lead to sexual assault. However, they may not take into account sociocultural factors that influence consent. In particular, the role of gender norms needs to be better understood. In-depth interviews about college students' sexual activity, including sexual consent communication, were conducted with 17 female and 13 male students at a large southern university during the spring 2013 semester. The interview protocol and analyses were guided by Carspecken's critical qualitative methodology, which seeks to understand both participants' explicit statements and implied underlying meanings and values. Themes and subthemes were identified through inductive analyses. Two overarching themes emerged: Students perceived a sexual double standard, and males viewed obtaining sex as a conquest. Subthemes related to the first theme reflected endorsement of traditional views of women's sexuality (the notions that "good girls" do not have sex, that women should privilege men's sexual needs over their own and that women "owe" men sex once men have "worked" for it). Subthemes related to the second theme reflected males' beliefs that sex is a commodity that pits women and men against one another, and that women can be "convinced" to have sex if they initially refuse. College students' consent communication may be influenced by gender norms that challenge assumptions of affirmative consent standards. Cultural shifts in students' views of sexuality may be necessary for affirmative consent policies to be effective.


Nestorone® as a Novel Progestin for Nonoral Contraception: Structure-Activity Relationships and Brain Metabolism Studies.
Nestorone® (NES) is a potent nonandrogenic progestin being developed for contraception. NES is a synthetic progestin that may possess neuroprotective and myelin regenerative potential as added health benefits. In receptor transactivation experiments, NES displayed greater potency than progesterone to transactivate the human progesterone receptor (PR). This was confirmed by docking experiments where NES adopts the same docking position within the PR ligand-binding domain (LBD) as progesterone and forms additional stabilizing contacts between 17α-acetoxy and 16-methylene groups and PR LBD, supporting its higher potency than progesterone. The analog 13-ethyl NES also establishes similar contacts as NES with Met909, leading to comparable potency as NES. In contrast, NES is not stabilized within the human androgen receptor LBD, leading to negligible androgen receptor transactivation. Because progesterone acts in the brain by both PR binding and indirectly via binding of the metabolite allopregnanolone to γ-aminobutyric acid type A receptor (GABAAR), we investigated if NES is metabolized to 3α, 5α-tetrahydronestorone (3α, 5α-THNES) in the brain and if this metabolite could interact with GABAAR. In female mice, low concentrations of reduced NES metabolites were identified by gas chromatography/mass spectrometry in both plasma and brain. Electrophysiological studies showed that 3α, 5α-THNES exhibited only limited activity to enhance GABAAR-evoked responses with WSS-1 cells and did not modulate synaptic GABAARs of mouse cortical neurons. Thus, the inability of reduced metabolite of NES (3α, 5α-THNES) to activate GABAAR suggests that the neuroprotective and myelin regenerative effects of NES are mediated via PR binding and not via its interaction with the GABAAR.


Honeycomb pattern formation by laser-beam filamentation in atomic sodium vapor.
We have observed transverse pattern formation leading to highly regular structures in both the near and far fields when a near-resonant laser beam propagates without feedback through an atomic sodium vapor. One example is a regular far-field honeycomb pattern, which results from the transformation of the laser beam within the vapor into a stable three-lobed structure with a uniform phase distribution and highly correlated power fluctuations. The predictions of a theoretical model of the filamentation process are in good agreement with these observations.


[A case of penile metastasis of malignant melanoma with priapism].
A metastatic penile tumor of malignant melanoma is very rare. The patient had priapism caused by metastatic penile tumor and the primary cancer was in the end stage. However, in this case, we could relieve the dysuria and pain by percutaneous cystostomy and partial penectomy. The corpus spongiosumcorpus cavernosum shunt could not relieve the priapism and might have accelerated the metastasis.


Identification and functional analysis of the NLP-encoding genes from the phytopathogenic oomycete Phytophthora capsici.
Phytophthora capsici is a hemibiotrophic, phytopathogenic oomycete that infects a wide range of crops, resulting in significant economic losses worldwide. By means of a diverse arsenal of secreted effector proteins, hemibiotrophic pathogens may manipulate plant cell death to establish a successful infection and colonization. In this study, we described the analysis of the gene family encoding necrosis- and ethylene-inducing peptide 1 (Nep1)-like proteins (NLPs) in P. capsici, and identified 39 real NLP genes and 26 NLP pseudogenes. Out of the 65 predicted NLP genes, 48 occur in groups with two or more genes, whereas the remainder appears to be singletons distributed randomly among the genome. Phylogenetic analysis of the 39 real NLPs delineated three groups. Key residues/motif important for the effector activities are degenerated in most NLPs, including the nlp24 peptide consisting of the conserved region I (11-aa immunogenic part) and conserved region II (the heptapeptide GHRHDWE motif) that is important for phytotoxic activity. Transcriptional profiling of eight selected NLP genes indicated that they were differentially expressed during the developmental and plant infection phases of P. capsici. Functional analysis of ten cloned NLPs demonstrated that Pc11951, Pc107869, Pc109174 and Pc118548 were capable of inducing cell death in the Solanaceae, including Nicotiana benthamiana and hot pepper. This study provides an overview of the P. capsici NLP gene family, laying a foundation for further elucidating the pathogenicity mechanism of this devastating pathogen.


Phylogenetic relationships and biogeographical patterns in Circum-Mediterranean subfamily Leuciscinae (Teleostei, Cyprinidae) inferred from both mitochondrial and nuclear data.
Leuciscinae is a subfamily belonging to the Cyprinidae fish family that is widely distributed in Circum-Mediterranean region. Many efforts have been carried out to deciphering the evolutionary history of this group. Thus, different biogeographical scenarios have tried to explain the colonization of Europe and Mediterranean area by cyprinids, such as the "north dispersal" or the "Lago Mare dispersal" models. Most recently, Pleistocene glaciations influenced the distribution of leuciscins, especially in North and Central Europe. Weighing up these biogeographical scenarios, this paper constitutes not only the first attempt at deciphering the mitochondrial and nuclear relationships of Mediterranean leuciscins but also a test of biogeographical hypotheses that could have determined the current distribution of Circum-Mediterranean leuciscins. A total of 4439 characters (mitochondrial + nuclear) from 321 individuals of 176 leuciscine species rendered a well-supported phylogeny, showing fourteen main lineages. Analyses of independent mitochondrial and nuclear markers supported the same main lineages, but basal relationships were not concordant. Moreover, some incongruence was found among independent mitochondrial and nuclear phylogenies. The monophyly of some poorly known genera such as Pseudophoxinus and Petroleuciscus was rejected. Representatives of both genera belong to different evolutionary lineages. Timing of cladogenetic events among the main leuciscine lineages was gained using mitochondrial and all genes data set. Adaptations to a predatory lifestyle or miniaturization have superimposed the morphology of some species. These species have been separated into different genera, which are not supported by a phylogenetic framework. Such is the case of the genera Pseudophoxinus and Petroleuciscus, which real taxonomy is not well known. The diversification of leuciscine lineages has been determined by intense vicariant events following the paleoclimatological and hydrogeological history of Mediterranean region. We propose different colonization models of Mediterranean region during the early Oligocene. Later vicariance events promoted Leuciscinae diversification during Oligocene and Miocene periods. Our data corroborate the presence of leuciscins in North Africa before the Messinian salinity crisis. Indeed, Messinian period appears as a stage of gradually Leuciscinae diversification. The rise of humidity at the beginning of the Pliocene promoted the colonization and posterior isolation of newly established freshwater populations. Finally, Pleistocene glaciations determined the current European distribution of some leuciscine species.


Penetration of Carbon Nanotubes into the Retinoblastoma Tumor after Intravitreal Injection in LH BETA T AG Transgenic Mice Reti-noblastoma Model.
To evaluate the penetration of carbon nanotubes (CNTs) throughout retinoblastoma in a transgenic mice model. CNTs functionalized with fluorescein isothiocyanate and targeting ligands biotin (CTN-FITC-Bio, 0.5mg/ml), or folic acid (CNT-FITC-FA, 0.5mg/ml) were injected into the vitreous of one eye of LH BETA T AG transgenic mice. Other eye did not receive any injection and was used as control. Three mice were sacrificed at days 1, 2, and 3. Eyes were enucleated and stained with 4,6-diamidino-2-phenylindole. The sections were imaged by fluorescent microscope. The images were transformed into grey-scale in MATLAB for intensity analysis. Background intensity was normalized by marking squares outside the eyeball and using the mean intensity of these squares. Fluorescent intensity (FI) for each image was measured by calculating the intensity of a same-sized square within retinoblastoma. Nine eyes of nine mice were included in each CNT-FITC-Bio and CNT-FITC-FA groups. The mean FI in CNT-FITC-Bio was 52.08 ± 6.33, 53.62 ± 9.00, and 65.54 ± 5.14 in days 1, 2, and 3, respectively. The mean FI in CNT-FITC-FA was 50.28 ± 7.37, 59.21 ± 6.43, and 58.38 ± 2.32 on days 1, 2, and 3, respectively. FI was significantly higher in eyes injected with CNT-FITC-Bio and CNT-FITC-FA compared to the control eyes (P = 0.02). There was no difference in FI between eyes with CNT-FITC-Bio and CNT-FITC-FA, and FI remained stable on days 1-3 in CNT-FITC-Bio, CNT-FITC-FA, and control eyes (P > 0.05). We observed higher FI in eyes with CNT-FITC-Bio and CNT-FITC-FA compared to control eyes, showing penetration of CNTs throughout retinoblastoma. CNTs can be a carrier candidate for imaging or therapeutic purposes in retinoblastoma.


Comparative bioinformatics analysis of prognostic and differentially expressed genes in non-muscle and muscle invasive bladder cancer.
Bladder cancer (BC) is classified into non-muscle (NMIBC) and muscle invasive (MIBC) diseases. Several molecular alterations were previously associated with NMIBC and MIBC, but few studies have systematically compared the molecular differences between these subtypes. Here, we analyzed prognostic and differentially expressed genes in NMIBC and MIBC, using an integrative bioinformatics approach. These genes were used in functional enrichment and co-expression protein interaction (COPI) network analyses to reveal common and exclusive biological functions involved in NMIBC and MIBC. In NMIBC, the enriched functions were related to oxidative stress response, cell cycle, glutathione metabolism, ubiquitination and protein translation. Conversely, enriched functions in MIBC were extracellular matrix organization, cell migration and actin cytoskeleton. Several genes in NMIBC did not overlap with those reported to MIBC, suggesting these subtypes may have distinct underlying mechanisms. Particularly, MIBC genes were enriched for functions involved in cell migration and invasion, which could help to molecularly differentiate NMIBC and MIBC. The analysis of COPI networks disclosed high centrality nodes that may be essential for NMIBC and MIBC. Further research will determine to which extent NMIBC and MIBC share common biological functions and identify potential candidates for the differential diagnosis, prognosis and treatment of NMIBC and MIBC. SIGNIFICANCE: This study has systematically compared prognostic and differentially expressed genes between non-muscle (NMIBC) and muscle invasive (MIBC) bladder cancer, using an integrative bioinformatics approach. Many genes and biological functions were exclusively associated with either NMIBC or MIBC, suggesting that these disease subtypes could be driven by distinct molecular mechanisms. Particularly, prognostic and differentially expressed genes in MIBC were involved in cell migration and invasion, which can help to molecularly differentiate the NMIBC and MIBC subtypes. Moreover, the analysis of co-expression protein interaction networks identified high centrality nodes that could be potential candidates for the prognosis and treatment of NMIBC and MIBC.


Human post-thymic precursor cells in health and disease. III. Role of the autologous rosette-forming T cells in the generation of spontaneous killer cells in the autologous mixed lymphocyte reaction.
Adult peripheral blood T lymphocytes activated in autologous mixed lymphocyte reactions (AMLR) exerted cytotoxicity on both phytohaemagglutinin-stimulated cells and Epstein-Barr virus-transformed cells. When autologous rosette-forming T cells were removed from total T lymphocytes, there was no generation of cytotoxicity. Re-addition of autologous rosette-forming T cells (Tar cells) to a population of T cells depleted of Tar cells restored the cytotoxic activity. Treatment of Tar cells with mitomycin C before their activation in AMLR caused loss of their capacity to give rise to killer cells. Furthermore, resting Tar cells did not show any cytotoxic activity as determined in the two different types of target cells used. Since Tar cells are able to differentiate into T gamma cells and since T gamma cells possess spontaneous cytotoxic activity, it is likely that Tar cells participate in the generation of spontaneous killer cells in AMLR as precursors of cytotoxic effector cells.


Precision Medicine in Low- and Middle-Income Countries.
Most cancer cases occur in low- and middle-income countries (LMICs). The sophisticated technical and human infrastructure needed for optimal diagnosis, treatment, and monitoring of cancers is difficult enough in affluent countries; it is especially challenging in LMICs. In Western, educated, industrial, rich, democratic countries, there is a growing emphasis on and success with precision medicine, whereby targeted therapy is directed at cancers based on the specific genetic lesions in the cancer. Can such precision approaches be delivered in LMICs? We offer some examples of novel partnerships and creative solutions that suggest that precision medicine may be possible in LMICs given heavy doses of will, creativity, and persistence and a little luck.


Surface-based approaches to spatial localization and registration in primate cerebral cortex.
Explicit surface reconstructions provide invaluable substrates for visualizing and analyzing the complex convolutions of cerebral cortex. This report illustrates the utility of surface-based atlases of human and macaque monkey for representing many aspects of cortical organization and function. These include a variety of cortical partitioning schemes plus an open-ended collection of complex activation patterns obtained from fMRI studies. Surface-based registration from one hemisphere to an atlas provides powerful approach to (i) objectively and quantitatively representing both the consistencies and the variability of the pattern of convolutions and the patterns of functional activation from any given task; and (ii) making comparisons across species and evaluating candidate homologies between cortical areas or functionally delineated regions.


Laboratory Assays Used to Rank Potato Cultivar Tolerance to Blackleg Showed That Tuber Vacuum Infiltration Results Correlate With Field Observations.
Seed potato certification data collected in Colorado from 2012 to 2016 was used to rank potato cultivar tolerance to blackleg. Five cultivars with different tolerance levels to blackleg ('Chipeta' ≈ 'Alegria' ≈ 'Lamoka' < 'Classic Russet' < 'Yukon Gem') were tested to determine whether we could validate field data with laboratory assays. A strain isolated from Colorado, Pectobacterium atrosepticum CW1-4, and the P. atrosepticum type strain, 33260, were used to inoculate plants through vacuum infiltration of tubers or stem inoculation. Disease was assessed with time-lapse video and by measuring lesion length and disease incidence. After vacuum infiltration of tubers with P. atrosepticum CW1-4 and 33260, cultivars varied in tolerance to soft rot ('Lamoka' < 'Classic Russet' < 'Alegria' ≈ 'Yukon Gem' < 'Chipeta'). Blackleg tolerance of the five cultivars also varied after vacuum infiltration ('Lamoka' < 'Alegria' ≈ 'Chipeta' < 'Classic Russet' ≈ 'Yukon Gem'). All cultivars were susceptible after stem inoculation with either strain. In this assay, 'Chipeta' had the longest lesions, and 'Lamoka' had the smallest lesions. Time-lapse video was used to assess 'Classic Russet' and 'Yukon Gem.' 'Yukon Gem' developed disease symptoms faster than 'Classic Russet,' but the difference was not significant. These results indicate that relative susceptibility of the five cultivars to P. atrosepticum depends on the assay used and that laboratory and greenhouse results differed from field observations.


Chemical components and their locations in the Verticillium fungicola cell wall.
The chemical structure of cell walls and fractions of Verticillium fungicola, a pathogen of Agaricus bisporus, as well as their corresponding ultrastructures were studied. There are at least three chemically distinct types of carbohydrate polymers: one yielding mannose with lower amounts of galactose and glucose (glucogalactomannan), another one composed mainly of glucose (glucan), and a third one containing only N-acetylglucosamine (chitin). Attempts were made to locate these materials in situ by comparing electron micrographs of shadowed and sectioned cell walls, and also by indirect immunofluorescence. It was shown that none of these polymers constituted a completely physically distinct layer, but there seem to be different solubility properties in the outer, inner, and intermediate layers. It was also shown that fibrillar material (chitin) embedded in cementing glucan constituted the residual inner fraction of the original wall material. Indirect immunofluorescence showed the location of a significant amount of glucogalactomannan on the surface of the walls in which rodlet structures were visualized by electron microscopy.


Long-term evolution of N-terminal pro-brain natriuretic peptide levels and exercise capacity in 132 left ventricular assist device recipients.
N-terminal pro-brain natriuretic peptide (NT-proBNP) is a widely used biomarker in clinical practice in the context of heart failure. Little is known about the long-term evolution of NT-proBNP levels in left ventricular assist device (LVAD) recipients. Besides this, the potential correlation of NT-proBNP with exercise capacity on the long term after LVAD implantation has not been previously studied. We retrospectively analysed 132 single-centre LVAD recipient records (HeartMate II/III; HeartWare; between March 2007 and January 2018; mean follow-up 559 days). Blood samples, 6-min walking test (6MWT) and maximal cardiopulmonary exercise test were performed in a standardized way. Pre-LVAD NT-proBNP levels were increased (9736 ± 1072 ng/l) and dropped significantly after implantation [14 days: 4360 ± 545 ng/l (P < 0.0001), 6 months: 1485 ± 139 ng/l (P < 0.0001)]. Afterwards a steady state was reached during follow-up (after 1 year: 1592 ± 214 ng/l, after 5 years: 1679 ± 311 ng/l). Submaximal exercise capacity significantly improved postoperatively [percentage of the predicted distance walked during the 6MWT 50 ± 2% (0-3 months); 61 ± 2% (3-6 months, P < 0.001)], with a steady state afterwards [66 ± 2% (6-12 months, P = 0.08); 64 ± 3%, P = 0.70 later on]. We found a gradual increment of percentage of the expected peak oxygen consumption postoperatively [44 ± 2% (0-3 months); 49 ± 2% (3-6 months); 52 ± 2% (6-12 months); 53 ± 1% (after 12 months)] with a significant improvement between 0 and 3 months versus after the first year on LVAD. Furthermore, we showed a significant moderate correlation between NT-proBNP levels and results at both the 6MWT (correlation coefficient: -0.31, P < 0.0001) and cardiopulmonary exercise testing (correlation coefficient: -0.28, P < 0.0001). NT-proBNP decreased on LVAD support. We showed that submaximal (6MWT) and maximal exercise capacity (cardiopulmonary exercise testing) improve after LVAD implantation and demonstrated an inverse correlation of both tests with NT-proBNP levels.


Transcription factors in the development of inner ear hair cells.
Inner ear hair cells are the sensory receptors that detect and convert sound vibrations and head movements into neural signals. However, in humans, these cells are unable to regenerate if they are damaged or lost. Over thepast decade,there has been an exponential increase in interest and progress in understanding of the development of the inner ear and of hair cells, aiming to gain insights into hair cell repair or even regeneration. In hair cell development, various transcription factors have been found to be involved in the processes of hair cell proliferation, differentiation and survival. Among these transcription factors, Math1, Gata3, Sox2 and Atoh1 have been highlighted for their crucial role in the fate of hair cells. In this article, we will summarize the current understanding of the role of transcription factors in hair cell development, focusing on the role and possible mechanisms of Math1, Gata3, Sox2 and Atoh1.


Quality assurance in mammography: status of residency education.
The purpose of this study was to determine to what extent radiology residents are being trained in quality assurance procedures for mammography. A telephone survey was conducted with 189 chief residents and 10 other senior residents from 199 of the 209 residency training programs in diagnostic radiology. Time spent on mammography rotations averaged 8 weeks. Only 10 residents (5%) were "very familiar" with the American College of Radiology (ACR) Mammography Accreditation Program; 72 (36%) were "not at all familiar" with it. Ninety-six (48%) knew that one technologist should be assigned quality control procedures. The majority did not know the recommended frequency for performing any of the five routine quality control procedures; only one knew the recommended frequencies for all five. Only twenty-seven (14%) knew the recommended maximum dose for a mammogram. Regarding biopsy yields and false-negative results: 92 residents (46%) sat in on outcome evaluation sessions; 54 (27%) played active roles, looking up and tabulating results; and 53 (27%) did not participate at all. Although time spent on mammography rotations has increased substantially, quality assurance issues are still largely neglected. It may not be reasonable for radiology residents to have detailed instruction in quality assurance procedures for mammography, but they should be more familiar with the general issues involved and the procedures intended to correct the problem of the variable quality of mammography in this country.


Myocardial preconditioning. Endogenous protection against infarction.
Even with heroic procedures, it is not yet possible to prevent cell death during a myocardial infarction; however, preconditioning has revealed an endogenous process capable of providing significant protection to the heart from such a fatal result. Mechanisms by which preconditioning operates have not yet been unraveled but its resolution has clear clinical significance.


Viscosity, hemostasis and inflammation in atherosclerotic heart diseases.
In atherosclerotic diseases vascular reserve is impaired and pressure gradient is decreased, therefore the reduced blood fluidity can lead to tissue ischemia more rapidly. In previous investigations we demonstrated the deterioration of plasma and whole blood viscosities in patients with acute ischemic coronary syndromes, chronic coronary artery disease, and percutaneous transluminal coronary angioplasty. Hemorheological variables (plasma and whole blood viscosities, hematocrit, red blood cell aggregation), hemostaseological parameters (plasma fibrinogen and von Willebrand factor (vWf)), and platelet aggregation were detected in more recent studies in cardio- and cerebrovascular diseases, and diabetes mellitus. Common risk factors (lipid profile, smoking, glucose level, previous diseases) and medication were also recorded. High portion of vascular patients were demonstrated to have poor ex vivo platelet inhibition. Effective antiplatelet treatment detected by aggregometry was related to lower plasma fibrinogen concentration and red blood cell aggregation and was also associated with less recurrent vascular events during the follow-up (p < 0.001). Beside the impaired hemorheological characteristics, the diabetic patients showed elevated vWf activity, which turned to correlate with hemoglobin A1c concentration (p < 0.01) rather than the fasting glucose. Our studies indicate the active role and interaction of hemorheological and hemostaseological factors in atherosclerotic heart diseases.


Brain-pituitary-gonadal axis during early development and sexual differentiation in the rainbow trout, Oncorhynchus mykiss.
Profiles of testosterone, 11-ketotestosterone, androstenedione, and estradiol were determined by RIA, and immunocytochemical techniques were employed to identify gonadotropin (GTH) I and II and gonadotropin releasing hormone (GnRH) in monosex and mixed sex populations of rainbow trout from 1 to 126 days postfertilization (dpf). Steroid levels were relatively high at 1 dpf and declined until 25 dpf. At 30 and 48 dpf (hatching) steroid levels increased slightly before they fell by 78 dpf and remained relatively constant thereafter. Trends toward differences in steroid content between males and females became evident around the time gonadal differentiation was histologically discernible (78 and 90 dpf). GTH I was present in the proximal pars distalis at all dates (48-126 dpf), whereas GTH II was not detectable. GnRH was found at all dates (48-126 dpf) and was distributed in several areas of the brain including the nucleus preopticus periventricularis, nucleus lateralis tuberis, and the pituitary in the region where GTH I was found. No differences were seen between males and females in the timing of appearance, localization, or intensity of staining of these peptide hormones. Given that the brain-pituitary-gonadal axis seems to be intact during the process of sexual differentiation and the fluctuations of steroid levels during this process, sex steroids may play the driving role for sexual differentiation of rainbow trout.


Potential active constituents responsible for treating acute pharyngitis in the flowers of Hosta plantaginea (Lam.) Aschers and their pharmacokinetics.
In Asia, the flower of Hosta plantaginea (Lam.) Aschers (hosta flower) is both an edible food and medicine. The hosta flower is often used as a material for cooking porridge and scented tea and in combination with other plants for alleviating pharyngitis. To clarify the anti-pharyngitis effect of the hosta flower and evaluate its potential active ingredients, an ethanol extract of the hosta flower was prepared and partially purified via chromatography on a column packed with D101 macroporous resin, which was eluted with different concentrations of ethanol. The anti-pharyngitis effect of the crude extract and the various partially purified fractions was examined in an ammonia-induced acute pharyngitis rat model. The 30% ethanol-eluted fraction significantly alleviated the severity of pharyngitis in the rat, as evaluated by changes in the levels of cytokines (IL-1β, IL-6, and TNF-α) and histological changes in the pharynx tissues. Subsequent HPLC-QTOF/MS (high-performance liquid chromatography coupled with quadrupole-time of flight tandem mass spectrometry) analysis of this fraction revealed kaempferol and its glycosides as the main components. Three of the main components were isolated and identified by 1D NMR. Their pharmacokinetics were studied for the first time by UHPLC-QQQ/MS (ultrahigh-performance liquid chromatography coupled with mass spectrometry). The findings suggested that the 30% ethanol-eluted fraction of the hosta flower extract may be a potential functional food for treating pharyngitis.


A trial studying approach to predict college achievement.
We argue that using trial studying is a reliable and valid way to select students for higher education. This method is based on a work sample approach often used in personnel selection contexts. We discuss that this method has predictive validity for study success, has high acceptance by stakeholders, and measures self-regulation in a high-stakes testing context that cannot be measured through self-report questionnaires. We suggest further research to implement this method to select students.


High quality visualization of biochemical pathways in BioPath.
Biochemical reactions form large and complex networks. Comprehensible visual representations of these networks help biochemists understand the relationships between the chemical components. Typically pathway diagrams are manually produced drawings. Because of the steady progress of knowledge and the complex relationships in these networks, automatic visualizations are necessary. Bio-Path is a system for the exploration and automatic visualization of biochemical pathways. It has been developed to obtain an electronic version of the well-known Boehringer Biochemical Pathways poster and offers new possibilities to find information and to navigate through pathways. BioPath has a specific database containing reactions and a hierarchical clustering of reactions and reaction networks. One feature is the automatic generation of pathways from the database and their high quality visualization. This paper states the requirements for the visualization of biochemical pathways, presents a layout algorithm and shows how BioPath can be used to explore biochemical reaction networks.


Intensive outpatient treatment for obsessive-compulsive spectrum disorders.
Exposure and response prevention (ERP) is the most effective treatment for obsessive-compulsive disorder (OCD), yet the intensive treatment schedule often described and recommended is not readily accessible to many populations. In the present article, the authors describe a time-limited, outpatient, intensive treatment for Obsessive Compulsive Spectrum Disorders in Israel. Working in the client's natural environment and making use of technology are particularly highlighted.


Exploring the therapeutic relationship through the reflective practice of nurses in acute mental health units: A qualitative study.
To explore the therapeutic relationship through the reflective practice of nurses in acute mental health units. In mental health units, the therapeutic relationship is especially relevant for increasing the effectiveness of nursing interventions. Reflective practice is considered an essential aspect for improving nursing care. Action and observation stages of a participatory action research project. Data were collected through reflective diaries designed for the guided description and reflection of practice interactions related to the therapeutic relationship and content analysis was applied. A total of 152 nurses from 18 acute mental health units participated. The COREQ guidelines were used. The results were classified into three categories as follows: (i) Nursing attitude as a core of the therapeutic relationship. For the nurses, the attitudinal component was key in the therapeutic relationship. (ii) Nursing practices that are essential to the therapeutic relationship. Nurses identified practices such as creating a conducive environment, using an appropriate verbal approach, offering help and working together with the patient as essential for establishing a therapeutic relationship in practice. (iii) Contextual factors affecting the therapeutic relationship. The nurses considered the patient's condition, the care dynamics of the unit and its regulations, as well as the structure and environment of the unit, as contextual factors involved the establishment of an adequate therapeutic relationship in daily clinical practice. This study has provided knowledge of the importance and role of the nurses' attitude in the context of the nurse-patient therapeutic relationship based on the reflections of nurses in mental health units regarding their own practice. These findings help nurses to increase awareness and develop improvement strategies based on their own knowledge and day-to-day difficulties. Moreover, managers can evaluate strategies that promote motivation and facilitate the involvement of nurses to improve the therapeutic relationship with patients.


Effect of contraction on mitogen-activated protein kinase signal transduction in skeletal muscle. Involvement Of the mitogen- and stress-activated protein kinase 1.
Growing evidence suggests that activation of mitogen-activated protein kinase (MAPK) signal transduction mediates changes in muscle gene expression in response to exercise. Nevertheless, little is known about upstream or downstream regulation of MAPK in response to muscle contraction. Here we show that ex vivo muscle contraction stimulates extracellular signal-regulated kinase 1 and 2 (ERK1/2), and p38(MAPK) phosphorylation. Phosphorylation of ERK1/2 or p38(MAPK) was unaffected by protein kinase C inhibition (GF109203X), suggesting that protein kinase C is not involved in mediating contraction-induced MAPK signaling. Contraction-stimulated phosphorylation of ERK1/2 and p38(MAPK) was completely inhibited by pretreatment with PD98059 (MAPK kinase inhibitor) and SB203580 (p38(MAPK) inhibitor), respectively. Muscle contraction also activated MAPK downstream targets p90 ribosomal S6 kinase (p90(Rsk)), MAPK-activated protein kinase 2 (MAPKAP-K2), and mitogen- and stress-activated protein kinase 1 (MSK1). Use of PD98059 or SB203580 revealed that stimulation of p90(Rsk) and MAPKAP-K2 most closely reflects ERK and p38(MAPK) stimulation, respectively. Stimulation of MSK1 in contracting skeletal muscle required the activation of both ERK and p38(MAPK). These data demonstrate that muscle contraction, separate from systemic influence, activates MAPK signaling. Furthermore, we are the first to show that contractile activity stimulates MAPKAP-K2 and MSK1.


Integrative Biological Chemistry Program Includes The Use Of Informatics Tools, GIS And SAS Software Applications.
Wesley College is a private, primarily undergraduate minority-serving institution located in the historic district of Dover, Delaware (DE). The College recently revised its baccalaureate biological chemistry program requirements to include a one-semester Physical Chemistry for the Life Sciences course and project-based experiential learning courses using instrumentation, data-collection, data-storage, statistical-modeling analysis, visualization, and computational techniques. In this revised curriculum, students begin with a traditional set of biology, chemistry, physics, and mathematics major core-requirements, a geographic information systems (GIS) course, a choice of an instrumental analysis course or a statistical analysis systems (SAS) programming course, and then, students can add major-electives that further add depth and value to their future post-graduate specialty areas. Open-sourced georeferenced census, health and health disparity data were coupled with GIS and SAS tools, in a public health surveillance system project, based on US county zip-codes, to develop use-cases for chronic adult obesity where income, poverty status, health insurance coverage, education, and age were categorical variables. Across the 48 contiguous states, obesity rates are found to be directly proportional to high poverty and inversely proportional to median income and educational achievement. For the State of Delaware, age and educational attainment were found to be limiting obesity risk-factors in its adult population. Furthermore, the 2004-2010 obesity trends showed that for two of the less densely populated Delaware counties; Sussex and Kent, the rates of adult obesity were found to be progressing at much higher proportions when compared to the national average.


Exosomes secreted under hypoxia enhance stemness in Ewing's sarcoma through miR-210 delivery.
Intercellular communication between tumor cells within the hypoxic microenvironment promote aggressiveness and poor patient prognoses for reasons that remain unclear. Here we show that hypoxic Ewing's sarcoma (EWS) cells release exosomes that promote sphere formation, a stem-like phenotype, in EWS cells by enhancing survival. Analysis of the hypoxic exosomal miRNA cargo identified a HIF-1α regulated miRNA, miR-210, as a potential mediator of sphere formation in cells exposed to hypoxic exosomes. Knockdown of HIF-1α in hypoxic EWS cells led to decreased exosomal miR-210 levels and reduced the capacity of hypoxic exosomes to form spheres. Inhibition of miR-210 in hypoxic spheres attenuated sphere formation and overexpression of miR-210 in normoxic spheres significantly enhanced the number of EWS spheres. Our results indicate that hypoxic exosomal miR-210 targets the proapoptotic protein CASP8AP2 in recipient cells. Moreover, the suppression of CASP8AP2 led to a reduction in apoptotic cells and increased sphere formation. Together, the findings in this study suggest that hypoxic exosomes promote stemness in EWS cells by delivering enriched miR-210 that is capable of down-regulating apoptotic pathways, resulting in the survival of cells with increased sphere formation. Future studies will further investigate the effects of EWS derived exosomal miRNAs on target genes and the role these interactions play in driving aggressiveness in hypoxic EWS tumors.


Reductive dechlorination of PCE and TCE by vitamin B12 and ZVMs.
The reductive dechlorination of tetrachloroethene (PCE) and trichloroethene (TCE) catalyzed by vitamin B12 was examined when zero valent metals (ZVMs) were used as bulk electron donors in batch reactors. UV-visible spectra showed that zinc reduces vitamin B12 Co(III) to vitamin B12 Co(I) through B12 Co(II) and iron reduces vitamin B12 Co(III) to vitamin B12 Co(II). Thus iron, the most popular ZVM reductant, does not have enough reduction potential toreduce vitamin B12 to the super-reduced vitamin B12(I), which has been shown to be an active species in reductive dechlorination. Dechlorination of PCE and TCE by iron and zinc in the presence of vitamin B12 showed that the zinc and vitamin B12 combination greatly enhances the reaction rates for both PCE and TCE, but iron and vitamin B12 result in an increase in reactivity only for PCE degradation, not for TCE degradation in comparison with metals only. This result indicates vitamin B12(I) is active towards both PCE and TCE degradation while vitamin B12(II) is active only towards PCE. Calculated activation energies for the dechlorination of PCE in the presence of Vitamin B12 showed that vitamin B12 lowered the activation energy about 40-60 kJ mol(-1) for both metals.


Human wild-type tau interacts with wingless pathway components and produces neurofibrillary pathology in Drosophila.
Pathologic alterations in the microtubule-associated protein tau have been implicated in a number of neurodegenerative disorders, including Alzheimer's disease (AD), progressive supranuclear palsy (PSP), and frontotemporal dementia (FTD). Here, we show that tau overexpression, in combination with phosphorylation by the Drosophila glycogen synthase kinase-3 (GSK-3) homolog and wingless pathway component (Shaggy), exacerbated neurodegeneration induced by tau overexpression alone, leading to neurofibrillary pathology in the fly. Furthermore, manipulation of other wingless signaling molecules downstream from shaggy demonstrated that components of the Wnt signaling pathway modulate neurodegeneration induced by tau pathology in vivo but suggested that tau phosphorylation by GSK-3beta differs from canonical Wnt effects on beta-catenin stability and TCF activity. The genetic system we have established provides a powerful reagent for identification of novel modifiers of tau-induced neurodegeneration that may serve as future therapeutic targets.


Primary cyst hydatid in the neck; report of one case.
Hydatid cyst is a parasitic disease that has been recognized endemically in many countries. Although the liver and lung are the most common organs involved by the disease, it may appear rarely in other tissues as a primary disease. In the ultrasonography of the neck taken from a 17 year old case who attended with a complaint of swelling in the neck, a partly regular, bounded cystic lesion of 33x28 mm in size was reported. When the cyst was thought to be hydatid during surgical exploration, this diagnosis was confirmed by histopathological verification of the specimen obtained. Whole abdomen ultrasonography and PA Chest Radiography were taken in order to determine whether there was another focus during the postoperative period. The Echinococcus ELISA test was performed as an immunological parameter. Treatment with Albendazole began after diagnosis during the postoperative period. Although hydatid cyst most commonly involves the liver and lung, it may be detected in all body tissues. Therefore hydatid cyst must be considered in the differential diagnosis in cystic lesions that are rarely encountered in body localizations in human, living in endemic regions.


Clinical evaluation of virus safety and inhibitor incidence: statistical considerations.
The basic statistical issue in pharmacovigilance is to claim, with reasonable certainty, that the incidence of an event of interest in a population of subjects is less than a certain value. How many subjects and events must be observed before such a claim can be made? A first situation of practical importance is when a product has been on the market for some period of time, and the safety of this product regarding some outcome of interest is questioned (for instance, the viral safety of blood products). Having observed a few occurrences of the event of interest, how confident can we be that the product is responsible for an elevation of the incidence of this event compared with the baseline incidence in a reference population? This issue will increasingly need to be addressed prospectively: how many subjects need to be treated and how many events observed, to be reasonably certain that a product is safe? Multi-stage designs are appropriate to address this question, yet they do not seem popular in pharmacovigilance. Such approaches could complement the standard recommendations to assess the safety of blood products, which are adequate as a first screen against major safety problems, but wholly inadequate for the long-term surveillance of subjects at risk of rare events. It will be argued that, from a regulatory perspective, the implementation of prospective protocols for pharmacovigilance, using appropriate statistical tools, would permit a tight control of the safety of new products, while making these products available as early as possible to the patients who need them.


Clinical Features, Treatments, and Prognosis of Intramedullary Spinal Cord Metastases From Lung Cancer: A Case Series and Systematic Review.
Intramedullary spinal cord metastasis from lung cancer (ISCM-LC) are increasing in prevalence. We aim to investigate its clinical features, treatments and prognosis. We reported 6 ISCM-LC cases and conducted a systematic review. Descriptive summarization, survival analysis, and multivariate Cox regression analysis were performed to comprehensively study the disease. All 6 patients had surgery. One used chemotherapy and the other had targeted drugs. Two patients died of ISCM-LC, 1 died of pulmonary embolism, 1 was alive, and 2 were lost to follow-up. We identified 197 ISCM-LC cases in literature with a mean age of 58 years and male preponderance. Small cell lung cancer accounted for 39.1%. The median interval from lung cancer to ISCM-LC was 7 months. Limb weakness was the most common symptom, and 45% cases progressed rapidly. Concomitant brain, leptomeningeal, and vertebral metastasis occurred to 55.8%, 20%, and 19.5%, respectively. Peritumoral edema appeared in 83.3%. Through survival analysis, we found sex, extraspinal metastasis, pathology, and improved symptoms affected the overall survival. Additionally, gross total resection (GTR) shared similar effectiveness with non-GTR, and other treatments following surgery hardly added extra effect. Surgery, improved symptoms, and sex were 3 independent prognostic factors after adjusting for confounding. The estimated median survival time was 5 months. The overall survival of ISCM-LC remains poor. Surgery is an independent protective factor for survival. Surgery should be considered once tolerated, and GTR might not be necessary. In addition, female patients with improved symptoms after intervention might have better overall survival.


Propofol anesthesia reduces emesis and airway obstruction in pediatric outpatients.
This study was an authors comparison of the effects of and recovery from anesthesia in healthy, premedicated pediatric outpatients who received either inhaled anesthetics (group 1) or propofol (group 2). Group 1 (n = 68) averaged 3.8 +/- 0.2 yr and weighed 17.7 +/- 0.8 kg, whereas group 2 (n = 75) averaged 3.3 +/- 0.2 yr and weighed 16.3 +/- 0.6 kg. The incidence of vomiting in the Postanesthetic Care Unit (PACU) and from discharge to the first postoperative morning was lower in the group receiving propofol (0% and 18%) than in the group receiving volatile agents (7% and 34%, P < 0.05). The incidence of airway obstruction during induction of anesthesia was higher (34% vs 10%, P < 0.01) in children receiving inhaled agent. Withdrawal of the extremity with propofol injection occurred in 14 (19%) patients. Arterial blood pressure was higher at loss of consciousness, laryngoscopy, and tracheal intubation in group 2 (P < 0.01). The length of time from the end of surgery to extubation of the trachea, recovery scores, and length of time spent in the PACU and the Day Surgery Unit were the same in the two groups. Pain scores obtained in the PACU were not different. The data indicate that propofol can be used safely to induce and maintain anesthesia in healthy pediatric outpatients. This coupled with the low incidence of vomiting and airway obstruction in the propofol group suggests distinct and compelling reasons to consider using the drug in this patient population.


Fluorescein and indocyanine green angiography after transpupillary thermotherapy of choroidal neovascularization. Early vascular changes.
Transpupillary thermotherapy (TTT) is currently being evaluated in clinical trials for the treatment of choroidal neovascularization (CNV). Preliminary results show that TTT achieves closure of CNV and reduction in subretinal exudation while preserving visual acuity. Fluorescein and indocyanine green angiography reveal increased leakage activity from CNV and collateral choroid within 1 hour after TTT and absence of dye leakage from CNV at 1 week after treatment. Optical coherence tomography confirms the angiographic findings. The early vascular changes after TTT of CNV are similar to those observed after PDT of CNV. Transpupillary thermotherapy and PDT might share common mechanisms of action. A placebo-controlled, multi-center trial (TTT4CNV) evaluating the long-term efficacy and visual implications of TTT in occult CNV is underway.


Feasibility of a new hollow fiber silicone membrane oxygenator for long-term ECMO application.
Currently in United States, there are no clinically-applicable hollow fiber extracorporeal membrane oxygenation (ECMO) oxygenators available. Therefore, our laboratory is in the process of developing a silicone hollow fiber membrane oxygenator for long-term ECMO usage. This oxygenator incorporates an ultrathin silicone hollow fiber. At this time, a specially-modified blood flow distributor (one chamber distributor) is centered in the module to prevent blood stagnation. An ex vivo long-term durability test for ECMO was performed using a healthy miniature calf for 2 weeks. Venous blood was drained from the left jugular vein of a calf, passed through the oxygenator and infused into the left carotid artery using a Gyro C1E3 centrifugal blood pump. A successful 2-week ex vivo experiment was performed. The O2 and CO2 gas transfer rates were maintained at the same value of 40 m/min at a blood flow rate of 1 L/min flow and V/Q=3 (V=gas flow rate; Q=blood flow rate). The plasma free hemoglobin was maintained around 5 mg/dl. After the experiment, no blood clot formation was observed in the module and no abnormal necropsy findings were found. These data suggest that the performance of this newly-improved oxygenator was stable, reliable, and acceptable for long-term ECMO.


Distinction of conjunctival melanocytic nevi from melanomas by fluorescence in situ hybridization.
A conjunctival melanocytic nevus may on occasion be difficult to distinguish from melanoma both clinically and histopathologically. An unambiguous correct diagnosis is critical because of major differences in management and prognosis. We evaluated a fluorescence in situ hybridization (FISH) assay, which has previously been shown to be of value for the diagnosis of melanocytic nevi and melanomas of the skin, using probes targeting 6p25 (RREB1), 6q23 (MYB), 11q13 (CCND1) and centromere 6 (CEP6), for its potential to assist in the distinction of conjunctival melanocytic nevi from melanomas. Four melanocytic nevi and eight melanomas of the conjunctiva were analyzed. Two of the melanomas were diagnostically problematic because of suboptimal histopathology. None of the conjunctival melanocytic nevi showed a level of chromosomal aberrations that met FISH criteria for a diagnosis of melanoma. All eight conjunctival melanomas (six unequivocal and two suspicious lesions) met FISH criteria for melanoma. Thus, results from FISH assay targeting 6p25, 6q23, 11q13 and centromere 6 correlated well with the histopathologic diagnoses and supported the histopathologic suspicion in two problem cases. The findings encourage further exploration of this technique as an ancillary method for the work-up of conjunctival melanocytic proliferations.


Phenotypic expression of Pseudomonas syringae avr genes in E. coli is linked to the activities of the hrp-encoded secretion system.
The specific recognition of elicitors produced by plant pathogenic bacteria carrying avirulence (avr) genes is postulated to initiate cellular defense responses in plants expressing corresponding resistance genes. The biochemical functions of most avr genes, however, are not known. A heterologous system was developed to phenotypically express Pseudomonas syringae avr genes in Escherichia coli cells that required the P. syringae hrp cluster. E. coli MC4100 transformants carrying the plasmic-borne P. syringae pv. syringae Pss61 hrp cluster and p. syringae pv. glycinea avrB expressed from a triple lacUV5 promoter gained the ability to elicit the hypersensitive response in soybean cultivars expressing Rpg1 and in an Arabidopsis thaliana accession expressing RPM1. Inactivation of energy transducing or outer membrane components of the hrp-encoded secretion system blocked phenotypic expression expression of avrB in E. coli, but deletions abolishing harpinPSS production had little effect on the production of the AvrB phenotype by the E. coli transformants. Phenotypic expression of avrA, AvrPto, avrRpm1, avrRpt2, and avrPph3 in E. coli was also shown to require the hrp cluster. The results indicate that generation of the Avr phenotype in P. syringae strains is specifically dependent on the secretion activities of the hrp cluster.


[TIVA with propofol-remifentanil or balanced anesthesia with sevoflurane-fentanyl in laparoscopic operations. Hemodynamics, awakening and adverse effects].
This study was designed to investigate the differences between TIVA with propofol/remifentanil (P/R) and balanced anaesthesia with sevoflurane/fentanyl (S/F) in gynaecological laparoscopic surgery. Emphasis was put on haemodynamic reaction, recovery profile, postoperative side effects and patient satisfaction. Sixty patients were randomly assigned to receive either total intravenous anaesthesia with propofol/remifentanil or anaesthesia with sevoflurane/fentanyl. After premedication (midazolam) and induction of anesthesia (propofol, atracurium) in both groups, either 1 microgram/kg fentanyl (S/F) or 1 microgram/kg remifentanil (P/R) was injected. Anaesthesia was maintained with 0.5 microgram/kg/min remifentanil (reduced to 50% after 5 min) and 0.06 microgram/kg/min propofol (P/R) or 1.7 vol % sevoflurane (S/F). Both groups were mechanically ventilated with 30% oxygen in air. The administration of sevoflurane and the infusion of the anaesthetics were adjusted to maintain a surgical depth of anaesthesia. For postoperative analgesia 1 g paracetamol was administered rectally prior to surgery. After recovery 20 mg/kg metamizol was given intravenously. At the end of surgery the anaesthetics were discontinued and haemodynamics, early emergence from anaesthesia, pain level, frequency of analgesic demand, incidence of PONV, shivering and patient satisfaction were assessed. Parameters were recorded for 24 h postoperatively. Recovery time after propofol-remifentanil anaesthesia was significantly shorter than after administration of sevoflurane and fentanyl (spontaneous ventilation 4.1 vs. 6.3 min, extubation 4.3 vs. 9.3 min, eye opening 4.4 vs 8.2 min, stating name 5.3 vs. 13.2 min, stating date of birth 5.4 vs. 13.3 min). There were no significant differences between the groups in shivering, pain score, analgesic demand and PONV. The S/F group responded to tracheal intubation with significantly higher blood pressure than the P/R group. During maintenance of anaesthesia heart rate in patients with S/F was significantly higher (P/R:HR max +16/-10; S/F:HR max +24/-0.). Measured on a scale (S/F 62%). Compared with patients given balanced anaesthesia with sevoflurane and fentanyl, TIVA with propofol and remifentanil proved to be particularly suited for gynaecological laparoscopic surgery. Its major advantages are haemodynamic stability, significantly shorter times of emergence, and the exceptional acceptance by the patients.


Is pericardial effusion a negative prognostic marker? Meta-analysis of outcomes of pericardial effusion.
The prognostic relevance and the prevalence of pericardial effusion in several diseases are not well established. The aim of this meta-analysis is to summarize the available evidence related to pericardial effusion prevalence and outcomes according to the cause. Articles investigating the prognosis of pericardial effusion were identified by literature search. Twenty-three studies were finally included (17 022 patients). All-cause mortality was the primary end-point. Secondary end-point was the prevalence of pericardial effusion in most common diseases related to this clinical condition. The pooled prevalence of pericardial effusion was 19.5% [95% confidence interval (CI): 14.3-26]. After a mean follow-up of 36 ± 23 months, the risk of death was higher in pericardial effusion patients [hazard ratio (HR) 1.59, 95% CI 1.37-1.85, P < 0.0001]. Stratifying for the main disease, pericardial effusion is associated with unfavourable outcome in all available subgroups: pulmonary arterial hypertension HR 1.53 (95% CI: 1.22-1.92; P < 0.0001), chronic heart failure (CHF) HR 1.53 (95% CI: 1.22-1.92; P < 0.0001), myocardial infarction HR 2.65 (95% CI: 1.4-4.99; P = 0.003) and malignancies HR 1.75 (95% CI: 1.09-2.81, P = 0.021). The lack of data concerning the idiopathic pericardial effusion does not permit a secure risk assessment but the average incidence of mortality is 14.5% (95% CI: 7.7-25.6). Pericardial effusion should be considered a marker of the severity of the underlying disease, whereas for idiopathic pericardial effusion the correlation with poor prognosis is less clear.


Non-invasive brain stimulation enhances the effects of melodic intonation therapy.
Research has suggested that a fronto-temporal network in the right hemisphere may be responsible for mediating melodic intonation therapy's (MIT) positive effects on speech recovery. We investigated the potential for a non-invasive brain stimulation technique, transcranial direct current stimulation (tDCS), to augment the benefits of MIT in patients with non-fluent aphasia by modulating neural activity in the brain during treatment with MIT. The polarity of the current applied to the scalp determines the effects of tDCS on the underlying tissue: anodal-tDCS increases excitability, whereas cathodal tDCS decreases excitability. We applied anodal-tDCS to the posterior inferior frontal gyrus of the right hemisphere, an area that has been shown both to contribute to singing through the mapping of sounds to articulatory actions and to serve as a key region in the process of recovery from aphasia, particularly in patients with large left hemisphere lesions. The stimulation was applied while patients were treated with MIT by a trained therapist. Six patients with moderate to severe non-fluent aphasia underwent three consecutive days of anodal-tDCS + MIT, and an equivalent series of sham-tDCS + MIT. The two treatment series were separated by 1 week, and the order in which the treatments were administered was randomized. Compared to the effects of sham-tDCS + MIT, anodal-tDCS + MIT led to significant improvements in fluency of speech. These results support the hypothesis that, as the brain seeks to reorganize and compensate for damage to left hemisphere language centers, combining anodal-tDCS with MIT may further recovery from post-stroke aphasia by enhancing activity in a right hemisphere sensorimotor network for articulation.


The Prevalence of Intestinal Parasitic Infections Among Kosovar and Serbian School-children in Kosovo.
The aim of this study was to estimate the prevalence and distribution of species of intestinal parasites in the Balkans on the example of Kosovar and Serbian residents from the region of Gnjilane ineastern Kosovo,where the epidemiology of intestinal parasitic infections remains unknown. Parasitological examination of stools pecimens was performed in 2017 and 2018. Stool samples were collected from asymptomatic school-children aged 6-17 years: 530 Kosovars from the municipality of Kaçanik and310 Serbs from the municipalities of Kamenica and Strpce. Each patient provided two stool samples collected every second day,fixed in SAF preservative and 70 % spiritus vini, transported to the Department of Epidemiology and Tropical Medicine at the Military Institute of Medicine in Poland,and tested by light microscopy using three diagnostic methods: directs mearin Lugol's solution,decantation in distilled water, and Fülleborn's flotation. A total of 101 Kosovar children (19.1 % of the study group)were found to be infected with intestinal parasites: nematodes (n=20), cestodes (n=2), trematodes (n=2), and protozoa (n=79). Only 13 Serbian children (4.2 %) were found to beinfected with nematodes (n=4),cestodes (n=3),and protozoa (n=6). Giardia intestinalis was themost prevalent intestinal parasite in both groups (14,9 % vs. 1.9 % children). The prevalence ofasymptomatic parasitic infections was significantly higher in Kosovars in comparison to the Serbsliving in the same region of eastern Kosovo. This fact shows that there may be significant differencesin the quality of health care and sanitation as well as feed hygiene between these two communities.


[Tissue distribution of mezlocillin (author's transl)].
Substantial amounts of mezlocillin are rapidly distributed in a wide range of tissues. After intravenous administration of doses ranging form 2 to 5 g, concentrations therapeutically active against most sensitive organisms were obtained in bone, prostate, skin, muscle and liver, as well as in wound exudates, pleural exudates, sputum and bronchial secretions. Mezlocillin did not easily cross the blood-brain barrier with normal meninges, but CSF concentrations when the meninges were inflamed. The antibiotic also crossed the placenta.


Radiovisiography: an update.
Comparatively little has been published regarding the recently developed (and rapidly developing) digital imaging dental radiographic system known as radiovisiography (RVG). This paper reviews the existing literature, describes various modifications and updates which have been made and discusses the clinical implications of RVG.


The impact of thromboemboli histology on the performance of a mechanical thrombectomy device.
Recently we published a novel method of thrombus preparation for use in a swine model for evaluation of thrombectomy designs. The clot (fibrin rich clot) is characterized by its similarity in histologic characteristics to the thromboemboli recovered from stroke patients. The purpose of this latest study was to evaluate if the performance of a mechanical thrombectomy device was affected by the histologic characteristics of thromboembolus. Erythrocyte rich clot, which was created using exogenous thrombin, and the novel experimental clot with abundance of fibrin/cellular component were used for comparison. The Merci clot retriever was used for the evaluation and the angiographic outcomes were analyzed. Two histologically different types of experimental clot, a conventionally used thrombin-induced clot (erythrocyte-rich clot) and a novel experimental clot that is similar in histologic characteristics to the thromboemboli recovered from patients with stroke (fibrin-rich clot), were prepared. Eight extracranial arteries in swine were occluded with erythrocyte-rich clot (group A), and 8 were occluded with fibrin-rich clot (group B), and MT by using the Merci clot retriever device was performed. Angiographic results in each group were evaluated. A total of 48 attempts at MT were made. The average number of attempts to achieve TIMI grade II or III recanalization was 2.75 times in group A and 4.5 times in group B (P < .001), respectively. The mean time to achieve recanalization was 15.5 minutes in group A and 81.5 minutes in group B (P < .01). Every vessel in group A showed recanalization (100%), whereas only 3 of 8 samples (37.5%) achieved recanalization in group B. In this model, arteries occluded by fibrin-rich clot demonstrated a significantly lower recanalization rate, lower final TIMI score, and a longer mean recanalization time than did arteries occluded by erythrocyte-rich clot. The angiographic outcome of MT by using the Merci clot retriever system was influenced by the histologic characteristics of the occluding thromboembolus.


Multiple Hypothesis Testing for Experimental Gingivitis Based on Wilcoxon Signed Rank Statistics.
Dental research often involves repeated multivariate outcomes on a small number of subjects for which there is interest in identifying outcomes that exhibit change in their levels over time as well as to characterize the nature of that change. In particular, periodontal research often involves the analysis of molecular mediators of inflammation for which multivariate parametric methods are highly sensitive to outliers and deviations from Gaussian assumptions. In such settings, nonparametric methods may be favored over parametric ones. Additionally, there is a need for statistical methods that control an overall error rate for multiple hypothesis testing. We review univariate and multivariate nonparametric hypothesis tests and apply them to longitudinal data to assess changes over time in 31 biomarkers measured from the gingival crevicular fluid in 22 subjects whereby gingivitis was induced by temporarily withholding tooth brushing. To identify biomarkers that can be induced to change, multivariate Wilcoxon signed rank tests for a set of four summary measures based upon area under the curve are applied for each biomarker and compared to their univariate counterparts. Multiple hypothesis testing methods with choice of control of the false discovery rate or strong control of the family-wise error rate are examined.


Prenatal family support, postnatal family support and postpartum depression.
Inadequate social support is an important determinant of postpartum depression (PPD). Social support for pregnant women consists of supports from various sources and can be measured at different gestation periods. Differentiating the effects of social support from different sources and measured at different gestation periods may have important implications in the prevention of PPD. In the family centred Chinese culture, family support is likely to be one of the most important components in social support. The aim of this study was to assess the association of prenatal family support and postnatal family support with PPD. A prospective cohort study was conducted between February and September 2007 in Hunan, China. Family support was measured with social support rating scale at 30-32 weeks of gestation (prenatal support) and again at 2 weeks of postpartum visit (postnatal support). PPD was defined as Edinburgh Postnatal Depression Scale (EPDS) score > or =13. A total of 534 pregnant women were included, and among them, 103 (19.3%) scored 13 or more on the EPDS. PPD was 19.4% in the lowest tertile versus 18.4% in the highest quartile (adjusted odds ratio: 1.04, 95% confidence interval 0.60, 1.80) for prenatal support from all family members, and PPD was 39.8% in the lowest tertile versus 9.6% in the highest tertile (adjusted odds ratio: 4.4, 95% confidence interval 2.3, 8.4) for postnatal support from all family members. Among family members, support from husband had the largest impact on the risk of developing PPD. Lack of postnatal family support, especially the support from husband, is an important risk factor of PPD.


Antibody reactivity to the HRES-1 endogenous retroviral element identifies a subset of patients with systemic lupus erythematosus and overlap syndromes. Correlation with antinuclear antibodies and HLA class II alleles.
To evaluate the correlation between the presence of antibodies to an endogenous retroviral element-encoded nuclear protein autoantigen, HRES-1, and the presence of other antinuclear antibodies and HLA class II alleles in patients with systemic lupus erythematosus (SLE) and overlap syndromes. Antibody reactivities to native and recombinant proteins and synthetic peptides were assessed by counterimmunoelectrophoresis, enzyme-linked immunosorbent assay, and Western blotting. HLA class II alleles were determined by oligonucleotide typing. Forty-eight percent of the 153 patients with autoimmune disease, and 52% of the subgroup with SLE, had HRES-1 antibodies. In contrast, 3.6% of 111 normal donors, and none of 42 patients with the acquired immunodeficiency syndrome or 50 asymptomatic human immunodeficiency virus 1-infected patients, had HRES-1 antibodies. Chi-square analyses revealed a significant association between anti-HRES-1 and anti-RNP and an inverse correlation between HRES-1 and Ro/La autoantibodies in patients with SLE or overlap syndromes. Antigenic epitopes of HRES-1 and the retroviral gag-related region of the 70-kd protein component of U1 small nuclear RNP, which share 3 consecutive highly charged amino acids (Arg-Arg-Glu), an additional Arg, and functionally similar Arg/Lys residues, represent cross-reactive epitopes between the two proteins. Selective removal of HRES-1 antibodies from sera of HRES-1-seropositive/RNP-seropositive patients by absorption on recombinant HRES-1/glutathione-S-transferase-conjugated agarose beads had no effect on anti-RNP reactivities. A comparative multivariate analysis of HLA class II genes revealed a differential segregation of DQB1 alleles in HRES-1-seropositive versus HRES-1-seronegative patients (P = 0.04). While a relative increase of DQB1*0402 among HRES-1-seropositive patients was noted across ethnic groups (P = 0.02), a decrease of DQB1*0201 and DQB1*0301 was found in white HRES-1-seropositive patients (P = 0.04). Autoantibodies to HRES-1 are detectable in a distinct subset of patients with autoimmune disease, primarily in those who do not have antibodies to Ro and La. Anti-HRES-1 and anti-RNP reactivities are mediated by cross-reactive but separate antibody molecules. HLA-DQB genes, rather than HLA-DRB or DQA genes, may have a more significant influence on generation of these antinuclear autoantibodies.


Cation-dependent transition between the quadruplex and Watson-Crick hairpin forms of d(CGCG3GCG).
The DNA oligonucleotide d(CGCG3GCG) can form either a Watson-Crick (WC) hairpin or a parallel-stranded quadruplex structure containing six G-quartet base pair assemblies. The exchange between these forms and single strands can be monitored using circular dichroism (CD). NMR results verified the assignment of specific CD bands to quadruplex and hairpin species, respectively. Cations stabilize the quadruplex in the order K+ greater than Ca2+ greater than Na+ greater than Mg2+ greater than Li+ and K+ greater than Rb+ greater than Cs+, indicating that K+ has an optimum ionic radius for complex formation and that ionic charge affects the extent of ion-induced stabilization. The quadruplex is stable in the presence of 40 mM K+ at micromolar DNA concentration and can be kinetically trapped as a metastable form when prepared at millimolar DNA concentration and then diluted into buffer containing 40 mM Na+. The concentration of K+ required to reverse the equilibrium from the hairpin to the quadruplex decreases sharply with increased DNA concentration. The quadruplex has an unusual pKa of ca. 6.8, indicating that C.C+ base pairs are probably forming. This system provides insights into some of the detailed structural characteristics of a ["G4-DNA".ion] complex and an experimental model for the recently proposed "sodium-potassium conformational switch" [Sen, D., & Gilbert, W. (1988) Nature 334, 364-366; Sen, D., & Gilbert, W. (1990) Nature 344, 410-414]. These results may help to explain the lack of cytidine residues in G-rich telomeric DNAs and suggest that methylation of GC-rich duplex DNAs in "GpC islands" may induce quadruplex formation within heterochromatin domains, resulting in reversible chromosomal condensation.


Body dysmorphic disorder: 30 cases of imagined ugliness.
Body dysmorphic disorder, preoccupation with an imagined defect in appearance, is included in DSM-III-R but has received little empirical study. The authors investigated the demographics, phenomenology, course, associated psychopathology, family history, and response to treatment in a series of 30 patients with the disorder. The patients (including 12 whose preoccupation was of probable delusional intensity) were assessed with a semistructured interview and the Structural Clinical Interview for DSM-III-R, and their family histories were obtained. The 17 men and 13 women reported a lifetime average of four bodily preoccupations, most commonly "defects" of the hair, nose, and skin. The average age at onset of body dysmorphic disorder was 15 years, and the average duration was 18 years. Seventy-three percent of the patients reported associated ideas or delusions of reference; 73%, excessive mirror checking; and 63%, attempts to camouflage their "deformities." As a result of their symptoms, 97% avoided usual social and occupational activities, 30% had been housebound, and 17% had made suicide attempts. Ninety-three percent of the patients had an associated lifetime diagnosis of a major mood disorder; 33%, a psychotic disorder; and 73%, an anxiety disorder. The patients generally responded poorly to surgical, dermatologic, and dental treatments and to adequate trials of most psychotropic medications, with the exception of fluoxetine and clomipramine (to which more than half had a complete or partial response). This often secret, chronic disorder can cause considerable distress and impairment, may be related to obsessive-compulsive disorder or mood disorder, and may respond to serotonin reuptake-blocking antidepressants.


Event-related EEG time-frequency analysis: an overview of measures and an analysis of early gamma band phase locking in schizophrenia.
An increasing number of schizophrenia studies have been examining electroencephalography (EEG) data using time-frequency analysis, documenting illness-related abnormalities in neuronal oscillations and their synchronization, particularly in the gamma band. In this article, we review common methods of spectral decomposition of EEG, time-frequency analyses, types of measures that separately quantify magnitude and phase information from the EEG, and the influence of parameter choices on the analysis results. We then compare the degree of phase locking (ie, phase-locking factor) of the gamma band (36-50 Hz) response evoked about 50 milliseconds following the presentation of standard tones in 22 healthy controls and 21 medicated patients with schizophrenia. These tones were presented as part of an auditory oddball task performed by subjects while EEG was recorded from their scalps. The results showed prominent gamma band phase locking at frontal electrodes between 20 and 60 milliseconds following tone onset in healthy controls that was significantly reduced in patients with schizophrenia (P = .03). The finding suggests that the early-evoked gamma band response to auditory stimuli is deficiently synchronized in schizophrenia. We discuss the results in terms of pathophysiological mechanisms compromising event-related gamma phase synchrony in schizophrenia and further attempt to reconcile this finding with prior studies that failed to find this effect.


Physical and biological targeting of radiotherapy.
Targeting of radiotherapy can be based on improving physical dose distribution of radiation delivered or on utilization of specific biological processes for targeting. Tools for physical targeting include brachytherapy, hadron therapy, conformal radiotherapy, stereotactic radiotherapy, stereotactically guided conformal fractionated radiotherapy, and intensity-modulated radiotherapy. Biological targeting can be based on specific metabolic pathways such as uptake of iodine-131 by thyroid cancer cells, difference in substrate uptake between cancer cells and normal cells (e.g. boronophenylalanine in boron neutron capture therapy), targeting of radioactive isotopes by specific carrier molecules (radioimmunotherapy, labeled hormone derivatives or bone-seeking phosphonates), or on the distribution of elements in the body (therapy of bone metastases with a calcium analog strontium-89 or phosphorus-32).


Fever, bacterial zoonoses, and One Health in sub-Saharan Africa.
Although often underappreciated, a number of bacterial zoonoses are endemic in Africa. Of these, brucellosis, leptospirosis, Q fever, and rickettsioses are responsible for a substantial proportion of febrile illness among patients seeking hospital care. In this paper, we discuss the aetiology, epidemiology, clinical presentation, diagnosis, treatment and prevention of these bacterial zoonoses. To prevent and control bacterial zoonoses, strategies targeting both animals and humans are crucial. These may lead to better outcomes than strategies based exclusively on treatment of human infections. Such strategies are referred to as the 'One Health' approach; the collaborative effort of multiple disciplines to attain optimal health for people, animals and the environment.


Atypical RNAs in the coelacanth transcriptome.
Circular and apparently trans-spliced RNAs have recently been reported as abundant types of transcripts in mammalian transcriptome data. Both types of non-colinear RNAs are also abundant in RNA-seq of different tissue from both the African and the Indonesian coelacanth. We observe more than 8,000 lincRNAs with normal gene structure and several thousands of circularized and trans-spliced products, showing that such atypical RNAs form a substantial contribution to the transcriptome. Surprisingly, the majority of the circularizing and trans-connecting splice junctions are unique to atypical forms, that is, are not used in normal isoforms.


Ethambutol toxicity: Expert panel consensus for the primary prevention, diagnosis and management of ethambutol-induced optic neuropathy.
Ethambutol use may lead to permanent vision loss by inducing a dose- and duration-dependent optic neuropathy. This has been of concern to ophthalmologists and physicians both; however, ethambutol continues to be used because of its anti-mycobacterial action with relative systemic safety. Recently, the guidelines of the Revised National Tuberculosis Control Programme of India have been revised to allow for fixed dose and longer duration of ethambutol use; this is likely to result in an increase in vision-threatening adverse effects. Taking cognizance of this, neuro-ophthalmologists, infectious disease specialists, and scientists met under the aegis of the Indian Neuro-Ophthalmology Society to deliberate on prevention, early diagnosis, and management of ethambutol-related toxic optic neuropathy. The recommendations made by the expert group focus on early suspicion of ethambutol toxicity through screening at the physician's office and opportunistic screening by the ophthalmologist. Further, they focus on an early diagnosis through identification of specific clinical biomarkers and on management in way of early stoppage of the drug and supportive therapy. This statement also describes the mechanism of reporting a case of toxic optic neuropathy through the Pharmacovigilance Programme of India and emphasizes the need for spreading awareness regarding vision-threatening adverse effects among patients and healthcare workers.


Orally active trifluoromethyl ketone inhibitors of human leukocyte elastase.
This paper describes the development a series of peptidyl trifluoromethyl ketone inhibitors of human leukocyte elastase which are found to have excellent pharmacological profiles. Methods have been developed that allow for the synthesis of these inhibitors in stereochemically pure form. Two of these compounds, 1k and 1l, have high levels of oral bioavailability in several species. Compound 1l has entered development as ZD8321 and is presently undergoing clinical evaluation. These compounds demonstrate that peptidyl trifluoromethyl ketone inhibitors can achieve high levels of oral activity and bioavailability, and therefore they may prove useful as therapeutic agents in the treatment of diseases in which elastase is implicated.


Outcomes of primary and catheter-related bacteremia. A cohort and case-control study in critically ill patients.
We studied a cohort of 2201 patients hospitalized in 15 French intensive care units (ICUs) for > or = 48 h during a 4-mo period to assess the incidence and outcomes of primary and definite catheter-related bloodstream (CRB) or secondary nosocomial bloodstream infection (NBSI). Variables associated with ICU death and duration of stay were determined by logistic regression, and attributable mortality and length of stay (LOS) from a nested matched case-control (96 pairs) study, stratified on the source of bacteremia. Bacteremia occurred in 5% (95% CI 4.1-6%) of patients with > or = 48 h ICU stay. Primary, CRB, and secondary NBSI accounted for 29%, 26%, and 45% of the 111 episodes, respectively. NBSI was associated with a markedly increased risk of death (OR = 4.6; 95% CI 2.9-7.1) and an attributable mortality of 35% (95% CI, 28%-47%). In the case-control study, the excess mortality was 20% (p = 0.03) in patients with primary bacteremia and CRB, and 55% (p < 0.001) for secondary bacteremia; in patients with CRB only, the excess mortality was 11.5%. The median excess ICU LOS in survivors of NBSI was 9.5 d, and was similar, irrespective of its source. The risk of mortality associated with primary and catheter-related bacteremia appears much lower than that of secondary bacteremia, but is sizable, and the excess LOS incurred by the various categories of bacteremia is comparable. Differentiating catheter-related bacteremia from both primary and other secondary bacteremia appears warranted in studies conducted in critically ill patients.


Zwitterionic digalactosylceramides from the earthworm, Pheretima asiatica.
Nine homogeneous glycosphingolipids were isolated from the earthworm, Pheretima asiatica (Annelida). All of them are digalactosylceramides carrying a choline phosphate group in the outer galactose moiety. Their full structures including the position of a phosphocholine unit were determined based on chemical and spectral evidence.


[Clinical observation on moxibustion combined with intermittent urethral catheterization for treatment of neurogenic vesical dysfunction].
To observe the effect of moxibustion combined with intermittent urethral catheterization on vesical function in the patient of neurogenic vesical dysfunction. Seventy-six cases were randomly divided into an observation group and a control group, 38 cases in each group. The control group was treated with routine intermittent urethral catheterization and the observation group with the intermittent urethral catheterization and moxibustion on Guanyuan (CV 4), Mingmen (GV 4), Zusanli (ST 36), etc. Changes of residual urine volume, white cell count and the balance state of the urinary bladder were selected as the indexes of therapeutic effect and the therapeutic effects were compared between the two groups. The total effective rate was 97.4% in the observation group and 79.0% in the control group with a significant difference between the two groups (P < 0.05); after treatment, there were significant differences between the two groups in the residual urine volume, the bladder volume and the case numbers reaching to the functional balance state of bladder (all P < 0.05), and there was no significant difference between the two groups in white cell count change (P > 0.05). Moxibustion combined with intermittent urethral catheterization can significantly improve vesical function in the patient of neurogenic vesical dysfunction, reducing residual urine volume, increasing volume of bladder, promoting the balance state of vesical function, but it is basically same as intermittent urethral catheterization in prevention of urinary infection and therapeutic effect.


A randomized double-blind trial of glypressin in the management of acute epistaxis.
This is the first randomised double-blind trial of glypressin in the treatment of acute epistaxis, where no localized bleeding point was found and where the patient would normally be treated with a form of nasal packing. It shows a statistically significant benefit with the intravenous drug compared to placebo. In addition, the dose of glypressin used to achieve control appears to be free of major side effects. Acute epistaxis is a common problem, nasal packing is unpleasant and not without side effects, and therefore an alternative form of treatment would have clear advantages. The mechanism of action of glypressin is discussed along with the implications of the results for the future role of glypressin in the treatment of acute epistaxis.


Inhibition of hepatitis B virus gene expression and replication by artificial microRNA.
To investigate the inhibitory effects of hepatitis B virus (HBV) replication and expression by transfecting artificial microRNA (amiRNA) into HepG2.2.15 cells. Three amiRNA-HBV plasmids were constructed and transfected into HepG2.2.15 cells. HBV antigen secretion was detected in the cells with transient and stable transfection by time-resolved fluoroimmunoassays (TRFIA). HBV DNA replication was examined by fluorescence quantitative PCR, and the level of HBV S mRNA was measured by semi-quantitative RT-PCR. The efficiency of transient transfection of the vectors into 2.2.15 cells was 55%-60%. All the vectors had significant inhibition effects on HBsAg and HBeAg at 72 h and 96 h after transfection (P < 0.01 for all). The secretion of HBsAg and HBeAg into the supernatant was inhibited by 49.8% +/- 4.7% and 39.9% +/- 6.7%, respectively, at 72 h in amiRNA-HBV-S608 plasmid transfection group. The copy of HBV DNA within culture supernatant was also significantly decreased at 72 h and 96 h after transfection (P < 0.01 for all). In the cells with stable transfection, the secretion of HBsAg and HBeAg into the supernatant was significantly inhibited in all three transfection groups (P < 0.01 for all, vs negative control). The copies of HBV DNA were inhibited by 33.4% +/- 3.0%, 60.8% +/- 2.3% and 70.1% +/- 3.3%, respectively. In HepG2.2.15 cells, HBV replication and expression could be inhibited by artificial microRNA targeting the HBV S coding region. Vector-based artificial microRNA could be a promising therapeutic approach for chronic HBV infection.


Workflow Integration of Research AI Tools into a Hospital Radiology Rapid Prototyping Environment.
The field of artificial intelligence (AI) in medical imaging is undergoing explosive growth, and Radiology is a prime target for innovation. The American College of Radiology Data Science Institute has identified more than 240 specific use cases where AI could be used to improve clinical practice. In this context, thousands of potential methods are developed by research labs and industry innovators. Deploying AI tools within a clinical enterprise, even on limited retrospective evaluation, is complicated by security and privacy concerns. Thus, innovation must be weighed against the substantive resources required for local clinical evaluation. To reduce barriers to AI validation while maintaining rigorous security and privacy standards, we developed the AI Imaging Incubator. The AI Imaging Incubator serves as a DICOM storage destination within a clinical enterprise where images can be directed for novel research evaluation under Institutional Review Board approval. AI Imaging Incubator is controlled by a secure HIPAA-compliant front end and provides access to a menu of AI procedures captured within network-isolated containers. Results are served via a secure website that supports research and clinical data formats. Deployment of new AI approaches within this system is streamlined through a standardized application programming interface. This manuscript presents case studies of the AI Imaging Incubator applied to randomizing lung biopsies on chest CT, liver fat assessment on abdomen CT, and brain volumetry on head MRI.


Regulation of nuclear localization: a key to a door.
Information can be transferred between the nucleus and the cytoplasm by translocating macromolecules across the nuclear envelope. Communication of extracellular or intracellular changes to the nucleus frequently leads to a transcriptional response that allows cells to survive in a continuously changing environment. Eukaryotic cells have evolved ways to regulate this movement of macromolecules between the cytoplasm and the nucleus such that the transfer of information occurs only under conditions in which a transcriptional response is required. This review focuses on the ways in which cells regulate movement of proteins across the nuclear envelope and the significance of this regulation for controlling diverse biological processes.


Parathyroid hormone as an anabolic therapy for women and men.
The quest for effective treatment of osteoporosis merits great attention because of the widespread, worldwide prevalence of this disease. Antiresorptive drugs reduce bone turnover, increase bone density and improve other aspects of bone quality. This article concentrates on another approach, namely the use of anabolic therapy in which the prospects for improving bone quality are even greater. Parathyroid hormone is available as the aminoterminal fragment, PTH(1-34), known as teriparatide, and is being studied in its full-length form, PTH(1-84). Teriparatide improves bone quality by actions on bone turnover, bone density, bone size and microarchitecture. In women, teriparatide reduces both vertebral and non-vertebral fractures. In individuals who have been treated previously with an antiresorptive agent, the ability of PTH to increase bone density may be reduced. Combination therapy with teriparatide or PTH(1-84) and an antiresorptive does not appear, at this time, to offer advantages over the use of parathyroid hormone alone. In order to maintain the densitometric gains in bone density with parathyroid hormone, it is important to follow its use with an antiresorptive agent.


Physiologic determinants of the anorexia of aging: insights from animal studies.
The anorexia of aging is a syndrome characterized by unexplained losses in food intake and body weight that occur near the end of life. Proposed etiologies cover a wide range of biological and psychological conditions. The observation of this phenomenon in older laboratory animals suggests that physiological changes play a significant causal role. Research on the neurochemical control of energy balance has received much attention in recent years, and age-related alterations in the neuropeptidergic effectors of food intake have been implicated in the anorexia of aging. This review provides an update on putative mechanisms underlying this dysregulation of feeding during advanced age.


Current clinical practice in cytoreductive surgery for advanced ovarian cancer: a European survey.
Surgical treatment of advanced ovarian cancer is a subject of fast development. The aim of this survey was to collect data on current surgical treatment from selected European gynecological oncology centers. A questionnaire has been sent to gynecological oncology centers from 18 countries across Europe, which are presented on the ESGO Web site. Data were collected on an anonymous basis. All questions were related to the cytoreductive surgery of advanced ovarian cancer. Response rate reached 63%, and data from 17 European countries were analyzed. The median number of new patients with ovarian cancer treated annually in a single centre was 95. Whereas 19% of centers perform infracolic omentectomy only, 81% carry on total omentectomy. Approximately half of the centers conduct appendectomy in all patients with advanced ovarian cancer, 1/3 only if the appendix is macroscopically involved. Lymphadenectomy is carried out in 20% of centers in all cases but in 31% only if no residual disease is achieved. Proportion of patients in whom colorectal resection is performed ranged from less than 5% to more than 40%. Colorectal resection, splenectomy and liver resection are conducted by gynecological oncologist in 27%, 46%, and 12%, respectively. There were substantial differences in the spectrum and complexity of procedures performed in patients with advanced ovarian cancer among large European gynecologic oncology centers. Tendency to more complex surgery was shown in centers with a higher number of cases. Selected bowel and upper abdominal procedures are already performed by gynecological oncologists in large proportion of centers, without existence of well-established postgraduate training program.


REM sleep behavior disorder in Parkinson's disease: A case from India confirmed with polysomnographic data.
Rapid eye movement (REM) sleep behavior disorder is a condition characterized by dream enactment. This condition may accompany neurodegenerative disorders. However, only a few reports from India are available, that too, without any polysomnographic evidence. We are reporting a case of REM sleep behavior disorder with polysomnographic evidence.


Oxygen uptake efficiency slope during exercise in adults with Down syndrome.
Persons with Down syndrome (DS) have low aerobic exercise capacity. The present authors sought to compare the oxygen uptake efficiency slope (OUES) between adults with and without DS performing graded exercise testing (GXT) and to investigate its relationship with peak oxygen uptake (VO2peak ) in both groups of participants. Twenty-three participants with DS and 24 non-disabled controls performed GXT with VO2 measurements. OUES was calculated from data of the first 75%, 90% and 100% GXT time. Multiple linear regression analyses were computed to explore associations between the independent (OUES and DS) and the dependent variables (VO2peak ). VO2peak , GXT time and OUES were lower in participants with DS (p < .05). OUES and DS explained 69.3% of the variance in VO2peak . Our findings show that OUES values are lower in persons with DS. Additionally, it was shown that OUES has predictive value for VO2peak estimations in DS.


Treatment of a Giant Aneurysm of the Right Middle Cerebral Artery with GDCs after Extracranial to Intracranial Bypass. A Technical Case Report.
A case of a giant aneurysm of the right middle cerebral artery treated with Guglielmi detachable coils is reported. Extracranial to intracranial bypass had previously been performed and surgical trapping had been attempted. During the endovascular procedure, balloon test occlusion of the middle cerebral artery was performed in order to demonstrate clinical and angiographic tolerance to parent vessel occlusion. A previous occlusion test in the right common carotid artery did not show sufficient flow through the bypass to perform safe parent vessel occlusion. Diagnostic imaging, the endovascular procedure, and haemodynamic aspects in cases in which parent vessel occlusion is required after extracranial-intracranial bypass are described and the literature is reviewed.