Blue Gravity Waves from BICEP2 ?

We present new constraints on the spectral index n_T of tensor fluctuations from the recent data obtained by the BICEP2 experiment. We found that the BICEP2 data alone slightly prefers a positive, "blue", spectral index with n_T=1.36\pm0.83 at 68 % c.l.. However, when a TT prior on the tensor amplitude coming from temperature anisotropy measurements is assumed we get n_T=1.67\pm0.53 at 68 % c.l., ruling out a scale invariant $n_T=0$ spectrum at more than three standard deviations. These results are at odds with current bounds on the tensor spectral index coming from pulsar timing, Big Bang Nucleosynthesis, and direct measurements from the LIGO experiment. Considering only the possibility of a "red", n_T<0 spectral index we obtain the lower limit n_T > -0.76 at 68 % c.l. (n_T>-0.09 when a TT prior is included).Comment: 3 Pages, 4 Figure

Tickling the CMB damping tail: scrutinizing the tension between the ACT and SPT experiments

The Atacama Cosmology Telescope (ACT) and the South Pole Telescope (SPT) have recently provided new, very precise measurements of the cosmic microwave background (CMB) anisotropy damping tail. The values of the cosmological parameters inferred from these measurements, while broadly consistent with the expectations of the standard cosmological model, are providing interesting possible indications for new physics that are definitely worth of investigation. The ACT results, while compatible with the standard expectation of three neutrino families, indicate a level of CMB lensing, parametrized by the lensing amplitude parameter A_L, that is about 70% higher than expected. If not a systematic, this anomalous lensing amplitude could be produced by modifications of general relativity or coupled dark energy. Vice-versa, the SPT experiment, while compatible with a standard level of CMB lensing, prefers an excess of dark radiation, parametrized by the effective number of relativistic degrees of freedom N_eff. Here we perform a new analysis of these experiments allowing simultaneous variations in both these, non-standard, parameters. We also combine these experiments, for the first time in the literature, with the recent WMAP9 data, one at a time. Including the Hubble Space Telescope (HST) prior on the Hubble constant and information from baryon acoustic oscillations (BAO) surveys provides the following constraints from ACT: N_eff=3.23\pm0.47, A_L=1.65\pm0.33 at 68% c.l., while for SPT we have N_eff=3.76\pm0.34, A_L=0.81\pm0.12 at 68% c.l.. In particular, the A_L estimates from the two experiments, even when a variation in N_eff is allowed, are in tension at more than 95% c.l..Comment: 7 pages, 7 figures, v.2. some typos and sentences correcte

Expression of erythroblastic leukemia viral oncogene homolog (erbBS) mRNAs and possible splice variants in 3T3-L1 preadipocytes

Previously, we studied the erythroblastic leukemia viral oncogene homolog (erbB) family of tyrosine kinase growth factor receptors in terms of protein expression, modulation and activation in the 3T3-L1 cell line. In the present study, the presence of full-length erbB mRNAs, and splice or proteolytic erbB variants, was evaluated using RT-PCR. Epidermal growth factor receptor (EGFR)/erbB1 expression was confirmed. Wild-type (wt) ErbB2, human erbB2 (HER2)-extracellular domain (ECD) and herstatin mRNA expression were analyzed. Restriction analysis confirmed wt expression. 3T3-L1 cells exhibited HER2-ECD and herstatin mRNA expression, although at extremely low levels (compared to the control cell lines). ErbB3 cDNA was amplified using mouse mammary tumors and rat acines as positive controls. ErbB4 was not positively identified in these cells. In conclusion, this study demonstrates that 3T3-L1 cells express EGFR/erbB1, erbB2 and erbB3, and possibly, certain erbB2 splice or proteolytic variants, which are worth pursuing.Fil: Pagano, Eleonora. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Pontificia Universidad Católica Argentina "Santa María de Los Buenos Aires"; ArgentinaFil: Fontana, Vanina Andrea. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Calvo, Juan Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentin

Oral plaque from Type 2 diabetic patients reduces the clonogenic capacity of dental pulp-derived mesenchymal stem cells

Type 2 diabetes (T2D) is a major metabolic disease and a key epigenetic risk factor for the development of additional clinical complications. Among them, periodontitis (PD), a severe inflammatory disease ascribable to a dysregulated physiology and composition of the oral microbiota, represents one of the most relevant complications. Periodontitis can impact the structure of the tooth and likely the stem and progenitor cell pool, which actively contributes to the periodontal microenvironment and homeostasis. Modifications of the oral plaque play a key role in the etiopathogenesis of PD caused by T2D. However, to what extent the biology of the progenitor pool is affected has still to be elucidated. In this short report, we aimed to explore the biological effects of oral plaque derived from T2D patients with PD in comparison to non-diabetic patients with PD. Oral plaque samples were isolated from T2D and non-diabetic subjects with PD. Dental pulp stem cells (DPSCs), derived from the premolar tooth, were conditioned for 21 days with oral plaque samples and tested for their clonogenic ability. Cultures were also induced to differentiate towards the osteogenic lineage, and ALP and osteocalcin gene expression levels were evaluated by real-time qPCR. Results have shown that the number of clones generated by DPSCs exposed to T2D oral plaque was significantly lower compared to controls (ctl). The multivariate analysis confirmed that the decreased clonogenesis was significantly correlated only with T2D diagnosis. Moreover, the effect of T2D oral plaque was specific to DPSCs. Indicators of osteogenic differentiation were not significantly affected. This study provides a new biological insight into the effects ascribable to T2D in PD

Platelet lysate-derived neuropeptide y influences migration and angiogenesis of human adipose tissue-derived stromal cells

Neuropeptide Y (NPY), a powerful neurotransmitter of the central nervous system, is a key regulator of angiogenesis and biology of adipose depots. Intriguingly, its peripheral vascular and angiogenic powerful activity is strictly associated to platelets, which are source of clinical hemoderivates, such as platelet lysate (PL), routinely employed in several clinical applications as wound healing, and to preserve ex vivo the progenitor properties of the adipose stromal cells pool. So far, the presence of NPY in PL and its biological effects on the adipose stromal cell fraction (ASCs) have never been investigated. Here, we aimed to identify endogenous sources of NPY such as PL-based preparations and to investigate which biological properties PL-derived NPY is able to exert on ASCs. The results show that PL contains a high amount of NPY, which is in part also excreted by ASCs when stimulated with PL. The protein levels of the three main NPY subtype receptors (Y1, Y2, Y5) are unaltered by stimulation of ASCs with PL, but their inhibition through selective pharmacological antagonists, considerably enhances migration, and a parallel reduction of angiogenic features of ASCs including decrease in VEGF mRNA and intracellular calcium levels, both downstream targets of NPY. The expression of VEGF and NPY is enhanced within the sites of neovascularisation of difficult wounds in patients after treatment with leuco-platelet concentrates. Our data highlight the presence of NPY in PL preparations and its peripheral effects on adipose progenitors

A comparison between 18F-FDG PET/CT imaging and biological and radiological findings in restaging of hepatoblastoma patients

Background. In this study we retrospectively evaluated if 18F-FDG-PET/CT provided incremental diagnostic information over CI in a group of hepatoblastoma patients performing restaging. Procedure. Nine patients (mean age: 5.9 years; range: 3.1–12 years) surgically treated for hepatoblastoma were followed up by clinical examination, serum α-FP monitoring, and US. CI (CT or MRI) and PET/CT were performed in case of suspicion of relapse. Fine-needle aspiration biopsies (FNAB) were carried out for final confirmation if the results of CI, PET/CT, and/or α-FP levels were suggestive of relapse. PET/CT and CI findings were analyzed for comparison purposes, using FNAB as reference standard. Results. α-FP level was suggestive of disease recurrence in 8/9 patients. Biopsy was performed in 8/9 cases. CI and PET/CT resulted to be concordant in 5/9 patients (CI identified recurrence of disease, but 18F-FDG-PET/CT provided a better definition of disease extent); in 4/9 cases, CI diagnostic information resulted in negative findings, whereas PET/CT correctly detected recurrence of disease. 18F-FDG-PET/CT showed an agreement of 100% (8/8) with FNAB results. Conclusions. 18F-FDG-PET/CT scan seems to better assess HB patients with respect to CI and may provide incremental diagnostic value in the restaging of this group of patients

Relationship between HDL Cholesterol Efflux Capacity, Calcium Coronary Artery Content, and Antibodies against ApolipoproteinA-1 in Obese and Healthy Subjects

AIMS: To explore the associations between cholesterol efflux capacity (CEC), coronary artery calcium (CAC) score, Framingham risk score (FRS), and antibodies against apolipoproteinA-1 (anti-apoA-1 IgG) in healthy and obese subjects (OS). METHODS AND RESULTS: ABCA1-, ABCG1-, passive diffusion (PD)-CEC and anti-apoA-1 IgG were measured in sera from 34 controls and 35 OS who underwent CAC score determination by chest computed tomography. Anti-apoA-1 IgG ability to modulate CEC and macrophage cholesterol content (MCC) was tested in vitro. Controls and OS displayed similar ABCG1-, ABCA1-, PD-CEC, CAC and FRS scores. Logistic regression analyses indicated that FRS was the only significant predictor of CAC lesion. Overall, anti-apoA-1 IgG were significantly correlated with ABCA1-CEC (r = 0.48, p &lt; 0.0001), PD-CEC (r = -0.33, p = 0.004), and the CAC score (r = 0.37, p = 0.03). ABCA1-CEC was correlated with CAC score (r = 0.47, p = 0.004) and FRS (r = 0.18, p = 0.29), while PD-CEC was inversely associated with the same parameters (CAC: r = -0.46, p = 0.006; FRS: score r = -0.40, p = 0.01). None of these associations was replicated in healthy controls or after excluding anti-apoA-1 IgG seropositive subjects. In vitro, anti-apoA-1 IgG inhibited PD-CEC (p &lt; 0.0001), increased ABCA1-CEC (p &lt; 0.0001), and increased MCC (p &lt; 0.0001). CONCLUSIONS: We report a paradoxical positive association between ABCA1-CEC and the CAC score, with the latter being inversely associated with PD in OS. Corroborating our clinical observations, anti-apoA-1 IgG enhanced ABCA1 while repressing PD-CEC, leading to MCC increase in vitro. These results indicate that anti-apoA-1 IgG have the potential to interfere with CEC and macrophage lipid metabolism, and may underpin paradoxical associations between ABCA1-CEC and cardiovascular risk

Ligand-based drug repurposing strategy identified SARS-CoV-2 RNA G-quadruplex binders

The single-stranded RNA genome of SARS-CoV-2 contains some G-quadruplex-forming G-rich elements which are putative drug targets. Here, we performed a ligand-based pharmacophore virtual screening of FDA approved drugs to find candidates targeting such RNA structures. Further in silico and in vitro assays identified three drugs as emerging SARS-CoV-2 RNA G-quadruplex binders

Health conditions of inmates in Italy

Abstract Background Several studies have shown that prison is characterized by a higher prevalence of chronic diseases than unconfined settings. The aim of this study was to describe the characteristics and health of inmates, focusing on internal diseases. Methods We designed a specific clinical record using the Python programming language. We considered all of the diagnoses according to the ICD-9-CM. Results Of a total of 17,086 inmates, 15,751 were enrolled in our study (M = 14,835; F = 869), corresponding to 92.2% of the entire inmate population (mean age of 39.6 years). The project involved a total of 57 detention facilities in six Italian regions (for a total of 28% of all detainees in Italy), as counted in a census taken on February 3, 2014. From the entire study sample, 32.5% of prisoners did not present any disorders, while 67.5% suffered from at least one disease. The most frequent pathologies were psychiatric (41.3%), digestive (14.5%), infectious (11.5%), cardiovascular (11.4%), endocrine, metabolic, and immune (8.6%), and respiratory (5.4%). Conclusion The findings showed that a large number of detainees were affected by several chronic conditions such as hypertension, dyslipidemia and type 2 diabetes mellitus, with an unusually high prevalence for such a young population. Therefore, a series of preventive measures is recommended to strengthen the entire care process and improve the health and living conditions of prisoners

Avaliação do desempenho de um serviço de dosagem de precisão para vancomicina em um hospital pediátrico de nível terciário

Introduction: Plasma level-based therapeutic drug monitoring of vancomycin is recommended in the treatment of complex pediatric infections in order to increase the probability of achieving safe and effective pharmacotherapy. Objective: To retrospectively evaluate the activities and performance of pharmacotherapeutic optimization based on vancomycin levels at a tertiary pediatric hospital between 2007 and 2020. Methods: Vancomycin levels of pediatric patients were analyzed, assessing care quality indicators and analytical verifications, as well as aspects related to teaching and research. The predictive performance of vancomycin levels was evaluated after adjustment of the therapeutic regimen using a population pharmacokinetic optimization program (BestDose v1.126) considering the coefficient of determination (R2), the mean absolute percentage error (MAPE), and the root mean square error (RMSE). Results: 13269 vancomycin level determinations were analyzed; 70% were trough levels and 81% belonged to patients in the intensive care units. Forty percent of the trough levels were within the therapeutic range when adjusted without software. Three hundred seventy-four pharmacotherapeutic interventions, of which 97% were accepted by the treating physician; 75% of the post-adjustment trough levels were within the therapeutic range, compared to 40% when the approach was empirical, a difference that was statistically significant (p=0.03). The values associated with predictive performance (n subgroup of patients = 91) were: R2=0.61, MAPE=28.16%, and RMSE=3.3, which all showed to be adequate. Conclusion: The performance of therapeutic vancomycin monitoring and related pharmacokinetic clinical activities showed to be good.Introducción: La dosificación de precisión a través del monitoreo de vancomicina basado en sus concentraciones plasmáticas (vancocinemia) es una práctica recomendada en el tratamiento de infecciones pediátricas de alta complejidad para aumentar la probabilidad de lograr una farmacoterapia segura&nbsp;y eficaz. Objetivo: Evaluar retrospectivamente las actividades y el desempeño relacionado a la optimización farmacoterapéutica basada en las vancocinemias (período 2007-2020) de un hospital pediátrico terciario. Métodos: Se analizaron las vancocinemias de pacientes pediátricos, estimándose indicadores de calidad asistencial y verificaciones analíticas, así como también aspectos relacionados a docencia e investigación. Se evaluó el desempeño predictivo&nbsp;de las concentraciones de vancomicina cuando se ajustaron los regímenes terapéuticos con un programa de optimización farmacocinética (BestDose v1.126) considerando el coeficiente de determinación (R2), el error porcentual absoluto medio (MAPE) y la raíz del error cuadrático medio (RMSE). Resultados: Se analizaron 13269 vancocinemias. El 70% fueron valles y el 81% pertenecieron a pacientes de Unidades de Cuidados Intensivos. El 40% de los valles se encontró dentro del margen terapéutico al ajustarse sin programa informático. Se realizaron 347 intervenciones farmacoterapéuticas, el 97% de las cuales fueron aceptadas por el médico tratante; el 75% de los valles posteriores al ajuste entraron en el margen terapéutico, valor significativamente mayor respecto al 40% de cuando el abordaje fue empírico (p=0.03). Los valores asociados al desempeño predictivo, (n subgrupo de pacientes = 91) fueron: R2=0.61, MAPE=28.16% y RMSE=3.3, mostrándose todos adecuados. Conclusión: Las actividades de monitoreo y farmacocinética clínica de vancomicina mostraron un buen rendimiento clínico.Introdução: A dosagem de precisão por meio do monitoramento da vancomicina com base em suas concentrações plasmáticas (vancocinemia) é uma prática recomendada no tratamento de infecções pediátricas de alta complexidade para aumentar a probabilidade de alcançar uma farmacoterapia segura e eficaz. Objetivo: Avaliar retrospectivamente as atividades e o desempenho relacionados à otimização farmacoterapêutica baseada em vancocinemias (período 2007-2020) de um hospital pediátrico terciário. Métodos: Foram analisadas as vancocinemias de pacientes pediátricos, estimando indicadores de qualidade assistencial e verificações analíticas, bem como aspectos relacionados ao ensino e à pesquisa. O desempenho preditivo das concentrações de vancomicina foi avaliado quando os regimes terapêuticos foram ajustados com um programa de otimização farmacocinética (BestDose v1.126) considerando o coeficiente de determinação (R2), o erro percentual absoluto médio (MAPE) e a raiz do erro quadrático médio (RMSE). Resultados: foram analisadas 13.269 vancocinemias. Setenta por cento eram vales e 81% pertenciam a pacientes em Unidades de Terapia Intensiva. Quarenta por cento dos vales estavam dentro da faixa terapêutica quando ajustados sem software. Foram realizadas 347 intervenções farmacoterapêuticas, das quais 97% foram aceitas pelo médico assistente; 75% dos vales pós-ajuste entraram na faixa terapêutica, valor significativamente maior comparado a 40% quando a abordagem foi empírica (p=0,03). Os valores associados ao desempenho preditivo (n subgrupo de pacientes = 91) foram: R2=0,61, MAPE=28,16% e RMSE=3,3, todos se mostrando adequados. Conclusão: As atividades de monitoramento e farmacocinética clínica da vancomicina apresentaram bom desempenho clínico