Phenotype and genotype correlation of the microconversion from the CYP21A1P to the CYP21A2 gene in congenital adrenal hyperplasia

Deficiency of 21-hydroxylase is the most common form of congenital adrenal hyperplasia (CAH-21OH). We determined by allele-specific PCR the frequency of microconversion in the CYP21A2 gene in 50 Brazilian patients with the classical (salt wasting: SW and simple virilizing: SV) forms and nonclassical (NC) form of CAH-21OH and correlated genotype with phenotype. Genotypes were classified into three mutation groups (A, B, and C) based on the amount of enzymatic activity in in vitro studies using adrenal cells. In 94 unrelated alleles, we diagnosed 76% of the affected alleles after screening for 7 microconversions. The most frequent point mutations observed in this series were I172N (19%), V281L (18%), and IVS2,A/C>G,-12 (15%). In the SW form, the most frequent mutation was IVS2,A/C>G,-12 (38%), in the SV form it was I172N (53%), and in the NC form it was V281L (57.7%). We observed a good correlation between genotype and phenotype. Discordance between genotype and phenotype was found in one SV patient with a mild mutation in one of the alleles (R356W/V281L). However, we cannot rule out the presence of an additional mutation in these alleles. We also observed a good correlation of genotype with 17alpha-hydroxyprogesterone, testosterone, and androstenedione levels. The severity of external genitalia virilization correlated with the severity of mutation. In conclusion, the frequencies described in the present study did not differ from worldwide studies, including the Brazilian population. The few differences observed may reflect individual sample variations. This new Brazilian cohort study suggests the presence of new mutations in Brazilian patients with different forms of CAH-21OH.1311131

Imatinib treatment of poor prognosis mesenchymal-type primary colon cancer: A proof-of-concept study in the preoperative window period (ImPACCT)

Background: The identification of four Consensus Molecular Subtypes (CMS1-4) of colorectal cancer forms a new paradigm for the design and evaluation of subtype-directed therapeutic strategies. The most aggressive subtype - CMS4 - has the highest chance of disease recurrence. Novel adjuvant therapies for patients with CMS4 tumours are therefore urgently needed. CMS4 tumours are characterized by expression of mesenchymal and stem-like genes. Previous pre-clinical work has shown that targeting Platelet-Derived Growth Factor Receptors (PDGFRs) and the related KIT receptor with imatinib is potentially effective against mesenchymal-type colon cance

"Ordinary, the same as anywhere else": notes on the management of spoiled identity in 'marginal' middle class neighbourhoods

Urban sociologists are becoming increasingly interested in neighbourhood as a source of middle-class identity. Particular emphasis is currently being given to two types of middle-class neighbourhood; gentrified urban neighbourhoods of ‘distinction’ and inconspicuous ‘suburban landscapes of privilege’. However, there has been a dearth of work on ‘marginal’ middle-class neighbourhoods that are similarly ‘inconspicuous’ rather than distinctive, but less exclusive, thus containing sources of ‘spoiled identity’. This article draws on data gathered from two ‘marginal’ middleclass neighbourhoods that contained a particular source of ‘spoiled identity’: social renters. Urban sociological analyses of neighbour responses to these situations highlight a process of dis-identification with the maligned object, which exacerbates neighbour differences. Our analysis of data from the ‘marginal’ middle-class neighbourhoods suggests something entirely different and Goffmanesque. This entailed the management of spoiled identity, which emphasized similarities rather than differences between neighbours.</p

Impact of a training project for primary health-care providers (FOCO project) in the HIV screening and HIV late diagnosis

Poster [P043] OBJECTIVE Reducing HIV late diagnosis remains an epidemiological challenge . The objective of this project was to promote early HIV diagnosis through the training of primary health - care providers (PHCP) . METHODS HIV specialists conducted training sessions in 108 primary care centers (PCC) from six Spanish regions during 2016 and 2017 , and with 1804 PHCP involved . The intervention was evaluated using a pre - experimental design collecting the dependent variables both in the six months before and after the intervention . Number of requests for HIV tests from the PCC trained and clinical data of new HIV diagnosed patients were collected . Parametric and non - parametric tests were used to assess differences between pre and post - intervention data . RESULTS 3. Differences in clinical variables in pre and post intervention period

Recent Results from PHOBOS at RHIC

The PHOBOS experiment at RHIC has recorded measurements for Au-Au collisions spanning nucleon-nucleon center-of-mass energies from 19.6 GeV to 200 GeV. Global observables such as elliptic flow and charged particle multiplicity provide important constraints on model predictions that characterize the state of matter produced in these collisions. The nearly 4 pi acceptance of the PHOBOS experiment provides excellent coverage for complete flow and multiplicity measurements. Results including beam energy and centrality dependencies are presented and compared to elementary systems.Comment: 4 pages, 4 figures, proceedings from PANIC02 in Osaka, Japa

Global Observations from PHOBOS

Particle production in Au+Au collisions has been measured in the PHOBOS experiment at RHIC for a range of collision energies. Three empirical observations have emerged from this dataset which require theoretical examination. First, there is clear evidence of limiting fragmentation. Namely, particle production in central Au+Au collisions, when expressed as $dN/d\eta'$ ($\eta' \equiv \eta-y_{beam}$), becomes energy independent at high energy for a broad region of $\eta'$ around $\eta'=0$. This energy-independent region grows with energy, allowing only a limited region (if any) of longitudinal boost-invariance. Second, there is a striking similarity between particle production in e+e- and Au+Au collisions (scaled by the number of participating nucleon pairs). Both the total number of produced particles and the longitudinal distribution of produced particles are approximately the same in e+e- and in scaled Au+Au. This observation was not predicted and has not been explained. Finally, particle production has been found to scale approximately with the number of participating nucleon pairs for $N_{part}>65$. This scaling occurs both for the total multiplicity and for high \pT particles (3 <\pT< 4.5 GeV/c).Comment: QM2002 plenary talk, 10 pages, 11 figure

Universal Behavior of Charged Particle Production in Heavy Ion Collisions

The PHOBOS experiment at RHIC has measured the multiplicity of primary charged particles as a function of centrality and pseudorapidity in Au+Au collisions at sqrt(s_NN) = 19.6, 130 and 200 GeV. Two kinds of universal behavior are observed in charged particle production in heavy ion collisions. The first is that forward particle production, over a range of energies, follows a universal limiting curve with a non-trivial centrality dependence. The second arises from comparisons with pp/pbar-p and e+e- data. N_tot/(N_part/2) in nuclear collisions at high energy scales with sqrt(s) in a similar way as N_tot in e+e- collisions and has a very weak centrality dependence. This feature may be related to a reduction in the leading particle effect due to the multiple collisions suffered per participant in heavy ion collisions.Comment: 4 Pages, 5 Figures, contributed to the Proceedings of Quark Matter 2002, Nantes, France, 18-24 July 200

Endoscopic mucosal resection (EMR) versus endoscopic submucosal dissection (ESD) for resection of large distal non-pedunculated colorectal adenomas (MATILDA-trial): Rationale and design of a multicenter randomized clinical trial

Background: Endoscopic mucosal resection (EMR) is currently the most used technique for resection of large distal colorectal polyps. However, in large lesions EMR can often only be performed in a piecemeal fashion resulting in relatively low radical (R0)-resection rates and high recurrence rates. Endoscopic submucosal dissection (ESD) is a newer procedure that is more difficult resulting in a longer procedural time, but is promising due to the high en-bloc resection rates and the very low recurrence rates. We aim to evaluate the (cost-)effectiveness of ESD against EMR on both short (i.e. 6 months) and long-term (i.e. 36 months). We hypothesize that in the short-run ESD is more time consuming resulting in higher healthcare costs, but is (cost-) effective on the long-term due to lower patients burden, a higher number of R0-resections and lower recurrence rates with less need for repeated procedures. Methods: This is a multicenter randomized clinical trial in patients with a non-pedunculated polyp larger than 20 mm in the rectum, sigmoid, or descending colon suspected to be an adenoma by means of endoscopic assessment. Primary endpoint is recurrence rate at follow-up colonoscopy at 6 months. Secondary endpoints are R0-resection rate, perceived burden and quality of life, healthcare resources utilization and costs, surgical referral rate, complication rate and recurrence rate at 36 months. Quality-adjusted-life-year (QALY) will be estimated taking an area under the curve approach and using EQ-5D-indexes. Healthcare costs will be calculated by multiplying used healthcare services with unit prices. The cost-effectiveness of ESD against EMR will be expressed as incremental cost-effectiveness ratios (ICER) showing additional costs per recurrence free patient and as ICER showing additional costs per QALY. Discussion: If this trial confirms ESD to be favorable on the long-term, the burden of extra colonoscopies and repeated procedures can be prevented for future patients. Trial registration:NCT02657044(Clinicaltrials.gov), registered January 8, 2016