Early onset of treatment effects with oral risperidone

BACKGROUND: The dogma of a delayed onset of antipsychotic treatment effects has been maintained over the past decades. However, recent studies have challenged this concept. We therefore performed an analysis of the onset of antipsychotic treatment effects in a sample of acutely decompensated patients with schizophrenia. METHODS: In this observational study, 48 inpatients with acutely decompensated schizophrenia were offered antipsychotic treatment with oral risperidone. PANSS-ratings were obtained on day 0, day 1, day 3, day 7 and day 14. RESULTS: Significant effects of treatment were already present on day 1 and continued throughout the study. The PANSS positive subscore and the PANSS total score improved significantly more than the PANSS negative subscore. CONCLUSION: Our results are consistent with the growing number of studies suggesting an early onset of antipsychotic treatment effects. However, non-pharmacological effects of treatment also need to be taken into consideration

Lysyl oxidase-like 2 (LOXL2), a new regulator of cell polarity required for metastatic dissemination of basal-like breast carcinomas

Basal-like breast carcinoma is characterized by the expression of basal/ myoepithelial markers, undifferentiated phenotype, highly aggressive behaviour and frequent triple negative status (ESR , PR , Her2neu ). We have previously shown that epithelial–mesenchymal transition (EMT) occurs in basal-like breast tumours and identified Lysyl-oxidase-like 2 (LOXL2) as an EMT player and poor prognosis marker in squamous cell carcinomas. We now show that LOXL2 mRNA is overexpressed in basal-like human breast carcinomas. Breast carcinoma cell lines with basal-like phenotype show a specific cytoplasmic/perinuclear LOXL2 expression, and this subcellular distribution is significantly associated with distant metastatic incidence in basal-like breast carcinomas. LOXL2 silencing in basal-like carcinoma cells induces a mesenchymal-epithelial transition (MET) associated with a decrease of tumourigenicity and suppression of metastatic potential. Mechanistic studies indicate that LOXL2 maintains the mesenchymal phenotype of basal-like carcinoma cells by a novel mechanism involving transcriptional downregulation of Lgl2 and claudin1 and disorganization of cell polarity and tight junction complexes. Therefore, intracellular LOXL2 is a new candidate marker of basal-like carcinomas and a target to block metastatic dissemination of this aggressive breast tumour subtypeThis work was supported by grants from the Spanish Ministry of Science and Innovation, MICINN, (SAF2007-53061; SAF2010-21143; Consolider Ingenio CSD2007/00017, to AC; SAF2007-63075; SAF2010-20175 to GM-B); Fundacion Mutua Madrileña (2007, 2009 to AC and GM-B); Instituto de Salud Carlos III (ISCIII) (PI 080971 to JP), and Junta de Andalucıa (PI-0384/2007; PI 080971, P07-CVI- 03100 to JP). FS and A Martı´n are recipients of JAE-pre and JAE-postdoc contracts from the Spanish Research Council (CSIC), respectively; MAC is founded by the RETICS (ISCIII)

A new approach to treatment of resistant gram-positive infections: potential impact of targeted IV to oral switch on length of stay

BACKGROUND: Patients prescribed intravenous (IV) glycopeptides usually remain in hospital until completion of this treatment. Some of these patients could be discharged earlier if a switch to an oral antibiotic was made. This study was designed to identify the percentage of inpatients currently prescribed IV glycopeptides who could be discharged earlier if a switch to an oral agent was used, and to estimate the number of bed days that could be saved. We also aimed to identify the patient group(s) most likely to benefit, and to estimate the number of days of IV therapy that could be prevented in patients who remained in hospital. METHODS: Patients were included if they were prescribed an IV glycopeptide for 5 days or more. Predetermined IV to oral antibiotic switch criteria and discharge criteria were applied. A multiple logistic regression model was used to identify the characteristics of the patients most likely to be suitable for earlier discharge. RESULTS: Of 211 patients, 62 (29%) could have had a reduced length of stay if they were treated with a suitable oral antibiotic. This would have saved a total of 649 inpatient days (median 5 per patient; range 1–54). A further 31 patients (15%) could have switched to oral therapy as an inpatient thus avoiding IV line use. The patients most likely to be suitable for early discharge were those with skin and soft tissue infection, under the cardiology, cardiothoracic surgery, orthopaedics, general medical, plastic surgery and vascular specialities, with no high risk comorbidity and less than five other regularly prescribed drugs. CONCLUSION: The need for glycopeptide therapy has a significant impact on length of stay. Effective targeting of oral antimicrobials could reduce the need for IV access, allow outpatient treatment and thus reduce the length of stay in patients with infections caused by antibiotic resistant gram-positive bacteria

The Zoning of Semi-Enclosed Bodies of Water According to the Sediment Pollution: The Bay of Algeciras as a Case Example

This paper reports a study of the occurrence and levels of polycyclic aromatic hydrocarbons (PAHs) in a bay characterised by a chronic persistent impact. A total of 55 sediment samples were taken at different depths up to 111 m in two sampling campaigns. Chemical analyses were carried out by gas chromatography-mass spectroscopy. The results indicate that: (1) significant spatial variations exist, (2) levels of PAHs are related more strongly to the spatial distribution of sediments than to mineralogy/granulometry, (3) the sediments are slightly-to-moderately contaminated by PAHs, and (4) these PAHs derive from pyrolytic and petrogenic sources. Through use of an innovative data classification system (proposed according to depth and spatial location of sampling points), and using factorial and cluster techniques, five zones have been differentiated depending on the contamination level and source

Prevalence of diabetes mellitus and impaired glucose regulation in Spain: the [email protected] Study

Introduction: atherosclerosis, blood vessel disease, is the main cause of cardiovascular disease associated with aging; comprising modifiable risk factors that increase because of this when it exists.Objective: to evaluate atherogenic markers and metabolic syndrome in older adults, with cardiovascular risk living in urban areas, Pinar del Río province. Methods: observational, descriptive and cross-sectional study, from the service of Clinical Laboratory at Abel Santamaría Cuadrado Teaching General Hospital  Pinar del Río with 60 years old and older patients from the urban areas, during the period 2013 - 2014. The target group included 588 patients. The sample comprised 100 patients who have at least two risk factors previously established for this study.Results: ample predominance of women (61.0 %), the risk factors of higher incidence were hypertension 67 %, and sedentary lifestyle 65 %, followed by obesity 48 %, diabetes mellitus 40 % along with smoking habit 32 %, obese with increased diameters of waist circumference 48 %, and dyslipidemia 49 %, those with high glycemic values in fasting 50 % of the sample. It was considered that 63 % of the patients studied suffer from metabolic syndrome.Conclusions: a high number of white-skin women, the predominant risk factors were hypertension followed by sedentary lifestyle, obesity, diabetes mellitus and smoking habit. Approximately half of the sample was obese with increased diameters of the waist circumference, a large part suffered from dyslipidemia and half of them showed high fasting blood glucose levels. The prevalence of metabolic syndrome was detected.IIntroducción: aterosclerosis, enfermedad de los vasos sanguíneos, principal causa de enfermedad cardiovascular vinculada al envejecimiento, con factores de riesgo modificables que se incrementan cuando esta existe.Objetivo: evaluar marcadores aterogénicos y síndrome metabólico en adultos mayores, con riesgo cardiovascular residentes en zonas urbanas de la provincia Pinar del Río.Métodos: estudio observacional, descriptivo, transversal, servicio de Laboratorio Clínico Hospital General Docente “Abel Santamaría Cuadrado” Pinar del Río, pacientes de 60 años y más de zonas urbanas, durante período 2013 - 2014. Universo de 588 pacientes. Muestra de 100 pacientes que posean mínimo de dos factores de riesgo establecidos con anterioridad para este estudio.Resultados: amplio predominio de las mujeres (61 %). Factores de riesgo de mayor incidencia hipertensión arterial 67 %, y sedentarismo 65 %, seguidos por obesidad 48 %, diabetes mellitus 40 % y hábito de fumar 32 %, obesos con diámetros aumentados de la circunferencia de la cintura 48 %, presentaban dislipidemia 49 % y tenían elevados valores de glucemia en ayunas el 50 % de la muestra. Se consideró que 63 % de los pacientes estudiados presentaron síndrome metabólico.Conclusiones: elevado número de mujeres de piel blanca, con factor de riesgo predominante de hipertensión arterial seguido por sedentarismo, obesidad, diabetes mellitus y hábito de fumar. Alrededor de la mitad de la muestra fueron obesos con diámetros aumentados de la circunferencia de la cintura, gran parte presentaban dislipidemia y la mitad altos valores de glucemia en ayunas. Se detecta prevalencia de síndrome metabólico

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Associations of iron metabolism genes with blood manganese levels: a population-based study with validation data from animal models

<p>Abstract</p> <p>Background</p> <p>Given mounting evidence for adverse effects from excess manganese exposure, it is critical to understand host factors, such as genetics, that affect manganese metabolism.</p> <p>Methods</p> <p>Archived blood samples, collected from 332 Mexican women at delivery, were analyzed for manganese. We evaluated associations of manganese with functional variants in three candidate iron metabolism genes: <it>HFE </it>[hemochromatosis], <it>TF </it>[transferrin], and <it>ALAD </it>[δ-aminolevulinic acid dehydratase]. We used a knockout mouse model to parallel our significant results as a novel method of validating the observed associations between genotype and blood manganese in our epidemiologic data.</p> <p>Results</p> <p>Percentage of participants carrying at least one copy of <it>HFE C282Y</it>, <it>HFE H63D</it>, <it>TF P570S</it>, and <it>ALAD K59N </it>variant alleles was 2.4%, 17.7%, 20.1%, and 6.4%, respectively. Percentage carrying at least one copy of either <it>C282Y </it>or <it>H63D </it>allele in <it>HFE </it>gene was 19.6%. Geometric mean (geometric standard deviation) manganese concentrations were 17.0 (1.5) μg/l. Women with any <it>HFE </it>variant allele had 12% lower blood manganese concentrations than women with no variant alleles (β = -0.12 [95% CI = -0.23 to -0.01]). <it>TF </it>and <it>ALAD </it>variants were not significant predictors of blood manganese. In animal models, <it>Hfe</it>^-/-mice displayed a significant reduction in blood manganese compared with <it>Hfe</it>^+/+mice, replicating the altered manganese metabolism found in our human research.</p> <p>Conclusions</p> <p>Our study suggests that genetic variants in iron metabolism genes may contribute to variability in manganese exposure by affecting manganese absorption, distribution, or excretion. Genetic background may be critical to consider in studies that rely on environmental manganese measurements.</p