MR and CT techniques

Magnetic resonance imaging (MRI) and computed tomography (CT) are routinely used in female pelvis imaging. MRI is primarily useful for locoregional characterization of benign and malignant diseases. CT is less accurate in locoregional evaluation, but remains useful in the follow-up of treated gynecological malignancies, as well as in the setting of emergency and in the guidance of biopsies. Although transabdominal and transvaginal ultrasonography (US) is not under the scope of this chapter, it remains the first-line imaging method for most gynecological conditions.info:eu-repo/semantics/publishedVersio

Understanding the agreements and controversies surrounding childhood psychopharmacology

The number of children in the US taking prescription drugs for emotional and behavioral disturbances is growing dramatically. This growth in the use of psychotropic drugs in pediatric populations has given rise to multiple controversies, ranging from concerns over off-label use and long-term safety to debates about the societal value and cultural meaning of pharmacological treatment of childhood behavioral and emotional disorders. This commentary summarizes the authors' eight main findings from the first of five workshops that seek to understand and produce descriptions of these controversies. The workshop series is convened by The Hastings Center, a bioethics research institute located in Garrison, New York, U.S.A

Gastric transit and small intestinal transit time and motility assessed by a magnet tracking system

<p>Abstract</p> <p>Background</p> <p>Tracking an ingested magnet by the Magnet Tracking System MTS-1 (Motilis, Lausanne, Switzerland) is an easy and minimally-invasive method to assess gastrointestinal transit. The aim was to test the validity of MTS-1 for assessment of gastric transit time and small intestinal transit time, and to illustrate transit patterns detected by the system.</p> <p>Methods</p> <p>A small magnet was ingested and tracked by an external matrix of 16 magnetic field sensors (4 × 4) giving a position defined by 5 coordinates (position: <b>x, y, z, and angle: θ, ϕ)</b>. Eight healthy subjects were each investigated three times: (1) with a small magnet mounted on a capsule endoscope (PillCam); (2) with the magnet alone and the small intestine in the fasting state; and (3) with the magnet alone and the small intestine in the postprandial state.</p> <p>Results</p> <p>Experiment (1) showed good agreement and no systematic differences between MTS-1 and capsule endoscopy when assessing gastric transit (median difference 1 min; range: 0-6 min) and small intestinal transit time (median difference 0.5 min; range: 0-52 min). Comparing experiments (1) and (2) there were no systematic differences in gastric transit or small intestinal transit when using the magnet-PillCam unit and the much smaller magnetic pill. In experiments (2) and (3), short bursts of very fast movements lasting less than 5% of the time accounted for more than half the distance covered during the first two hours in the small intestine, irrespective of whether the small intestine was in the fasting or postprandial state. The mean contraction frequency in the small intestine was significantly lower in the fasting state than in the postprandial state (9.90 min^-1vs. 10.53 min^-1) (p = 0.03).</p> <p>Conclusion</p> <p>MTS-1 is reliable for determination of gastric transit and small intestinal transit time. It is possible to distinguish between the mean contraction frequency of small intestine in the fasting state and in the postprandial state.</p

Facts, values, and Attention-Deficit Hyperactivity Disorder (ADHD): an update on the controversies

The Hastings Center, a bioethics research institute, is holding a series of 5 workshops to examine the controversies surrounding the use of medication to treat emotional and behavioral disturbances in children. These workshops bring together clinicians, researchers, scholars, and advocates with diverse perspectives and from diverse fields. Our first commentary in CAPMH, which grew out of our first workshop, explained our method and explored the controversies in general. This commentary, which grows out of our second workshop, explains why informed people can disagree about ADHD diagnosis and treatment. Based on what workshop participants said and our understanding of the literature, we make 8 points. (1) The ADHD label is based on the interpretation of a heterogeneous set of symptoms that cause impairment. (2) Because symptoms and impairments are dimensional, there is an inevitable "zone of ambiguity," which reasonable people will interpret differently. (3) Many other variables, from different systems and tools of diagnosis to different parenting styles and expectations, also help explain why behaviors associated with ADHD can be interpreted differently. (4) Because people hold competing views about the proper goals of psychiatry and parenting, some people will be more, and others less, concerned about treating children in the zone of ambiguity. (5) To recognize that nature has written no bright line between impaired and unimpaired children, and that it is the responsibility of humans to choose who should receive a diagnosis, does not diminish the significance of ADHD. (6) Once ADHD is diagnosed, the facts surrounding the most effective treatment are complicated and incomplete; contrary to some popular wisdom, behavioral treatments, alone or in combination with low doses of medication, can be effective in the long-term reduction of core ADHD symptoms and at improving many aspects of overall functioning. (7) Especially when a child occupies the zone of ambiguity, different people will emphasize different values embedded in the pharmacological and behavioral approaches. (8) Truly informed decision-making requires that parents (and to the extent they are able, children) have some sense of the complicated and incomplete facts regarding the diagnosis and treatment of ADHD

The Novel μ-Opioid Receptor Antagonist GSK1521498 Decreases Both Alcohol Seeking and Drinking: Evidence from a New Preclinical Model of Alcohol Seeking.

Distinct environmental and conditioned stimuli influencing ethanol-associated appetitive and consummatory behaviors may jointly contribute to alcohol addiction. To develop an effective translational animal model that illuminates this interaction, daily seeking responses, maintained by alcohol-associated conditioned stimuli (CSs), need to be dissociated from alcohol drinking behavior. For this, we established a procedure whereby alcohol seeking maintained by alcohol-associated CSs is followed by a period during which rats have the opportunity to drink alcohol. This cue-controlled alcohol-seeking procedure was used to compare the effects of naltrexone and GSK1521498, a novel selective μ-opioid receptor antagonist, on both voluntary alcohol-intake and alcohol-seeking behaviors. Rederived alcohol-preferring, alcohol-nonpreferring, and high-alcohol-drinking replicate 1 line of rats (Indiana University) first received 18 sessions of 24 h home cage access to 10% alcohol and water under a 2-bottle choice procedure. They were trained subsequently to respond instrumentally for access to 15% alcohol under a second-order schedule of reinforcement, in which a prolonged period of alcohol-seeking behavior was maintained by contingent presentations of an alcohol-associated CS acting as a conditioned reinforcer. This seeking period was terminated by 20 min of free alcohol drinking access that achieved significant blood alcohol concentrations. The influence of pretreatment with either naltrexone (0.1-1-3 mg/kg) or GSK1521498 (0.1-1-3 mg/kg) before instrumental sessions was measured on both seeking and drinking behaviors, as well as on drinking in the 2-bottle choice procedure. Naltrexone and GSK1521498 dose-dependently reduced both cue-controlled alcohol seeking and alcohol intake in the instrumental context as well as alcohol intake in the choice procedure. However, GSK1521498 showed significantly greater effectiveness than naltrexone, supporting its potential use for promoting abstinence and preventing relapse in alcohol addiction.The present study was funded by Medical Research Council Programme Grant (no. G1002231) and by GlaxoSmithKline (GSK), which has a commercial interest in GSK1521498. Charles R. Goodlett was funded by a grant from the IUPUI International Development Fund, which supported his sabbatical leave at the University of Cambridge. Maria Pilar Garcia-Pardo was funded by Val+id para investigadores en formación (Conselleria de educacion, Generalitat Valenciana), which also supported her stay at the University of Cambridge (January-April 2014) as a Visiting Student.This is the accepted manuscript. The final version is available from NPG at http://dx.doi.org/10.1038/npp.2015.15

The effects of patient characteristics on ADHD diagnosis and treatment: a factorial study of family physicians

<p>Abstract</p> <p>Background</p> <p>Attention Deficit Hyperactivity Disorder (ADHD) is a costly and prevalent disorder in the U.S., especially among youth. However, significant disparities in diagnosis and treatment appear to be predicted by the race and insurance status of patients.</p> <p>Methods</p> <p>This study employed a web-based factorial survey with four ADHD cases derived from an ADHD clinic, two diagnosed with ADHD in actual evaluation, and two not. Randomized measures included race and insurance status of the patients. Participants N = (187) included clinician members of regional and national practice-based research networks and the U.S. clinical membership of the Society of Teachers of Family Medicine. The main outcomes were decisions to 1) diagnose and 2) treat the cases, based upon the information presented, analyzed via binary logistic regression of the randomized factors and case indicators on diagnosis and treatment.</p> <p>Results</p> <p>ADHD-positive cases were 8 times more likely to be diagnosed and 12 times more likely to be treated, and the male ADHD positive case was more likely to be diagnosed and treated than the female ADHD positive case. Uninsured cases were significantly more likely to be treated overall, but male cases that were uninsured were about half as likely to be diagnosed and treated with ADHD. Additionally, African-American race appears to increase the likelihood of medicinal treatment for ADHD and being both African-American and uninsured appears to cut the odds of medicinal treatment in half, but not significantly.</p> <p>Conclusions</p> <p>Family physicians were competent at discerning between near-threshold ADHD-negative and ADHD positive cases. However, insurance status and race, as well as gender, appear to affect the likelihood of diagnosis and treatment for ADHD in Family Medicine settings.</p

Nitroxyl (HNO) Stimulates Soluble Guanylyl Cyclase to Suppress Cardiomyocyte Hypertrophy and Superoxide Generation

Background: New therapeutic targets for cardiac hypertrophy, an independent risk factor for heart failure and death, are essential. HNO is a novel redox sibling of NON attracting considerable attention for the treatment of cardiovascular disorders, eliciting cGMP-dependent vasodilatation yet cGMP-independent positive inotropy. The impact of HNO on cardiac hypertrophy (which is negatively regulated by cGMP) however has not been investigated. Methods: Neonatal rat cardiomyocytes were incubated with angiotensin II (Ang II) in the presence and absence of the HNO donor Angeli’s salt (sodium trioxodinitrate) or B-type natriuretic peptide, BNP (all 1 mmol/L). Hypertrophic responses and its triggers, as well as cGMP signaling, were determined. Results: We now demonstrate that Angeli’s salt inhibits Ang II-induced hypertrophic responses in cardiomyocytes, including increases in cardiomyocyte size, de novo protein synthesis and b-myosin heavy chain expression. Angeli’s salt also suppresses Ang II induction of key triggers of the cardiomyocyte hypertrophic response, including NADPH oxidase (on both Nox2 expression and superoxide generation), as well as p38 mitogen-activated protein kinase (p38MAPK). The antihypertrophic, superoxide-suppressing and cGMP-elevating effects of Angeli’s salt were mimicked by BNP. We also demonstrate that the effects of Angeli’s salt are specifically mediated by HNO (with no role for NON or nitrite), with subsequent activation of cardiomyocyte soluble guanylyl cyclase (sGC) and cGMP signaling (on both cGMP-dependen

Environmental Acidification Drives S. pyogenes Pilus Expression and Microcolony Formation on Epithelial Cells in a FCT-Dependent Manner

Group A Streptococcus (GAS, Streptococcus pyogenes) is a Gram-positive human pathogen responsible for a diverse variety of diseases, including pharyngitis, skin infections, invasive necrotizing fasciitis and autoimmune sequelae. We have recently shown that GAS cell adhesion and biofilm formation is associated with the presence of pili on the surface of these bacteria. GAS pilus proteins are encoded in the FCT (Fibronectin- Collagen-T antigen) genomic region, of which nine different variants have been identified so far. In the present study we undertook a global analysis of GAS isolates representing the majority of FCT-variants to investigate the effect of environmental growth conditions on their capacity to form multicellular communities. For FCT-types 2, 3, 5 and 6 and a subset of FCT-4 strains, we observed that acidification resulting from fermentative sugar metabolism leads to an increased ability of the bacteria to form biofilm on abiotic surfaces and microcolonies on epithelial cells. The higher biofilm forming capacity at low environmental pH was directly associated with an enhanced expression of the genes encoding the pilus components and of their transcription regulators. The data indicate that environmental pH affects the expression of most pilus types and thereby the formation of multicellular cell-adhering communities that assist the initial steps of GAS infection