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Local formation and action of estrogens have crucial roles in hormone dependent cancers and benign diseases like endometriosis. Drugs that are currently used for the treatment of these diseases act at the receptor and at the pre-receptor levels, targeting the local formation of estrogens. Since 1980s the local formation of estrogens has been targeted by inhibitors of aromatase that catalyses their formation from androgens. Steroidal and non-steroidal inhibitors have successfully been used to treat postmenopausal breast cancer and have also been evaluated in clinical studies in patients with endometrial, ovarian cancers and endometriosis. Over the past decade also inhibitors of sulfatase that catalyses the hydrolysis of inactive estrogen-sulfates entered clinical trials for treatment of breast, endometrial cancers and endometriosis, with clinical effects observed primarily in breast cancer. More recently, inhibitors of 17beta-hydroxysteroid dehydrogenase 1, an enzyme responsible for formation of the most potent estrogen, estradiol, have shown promising results in preclinical studies and have already entered clinical evaluation for endometriosis. This review aims to provide an overview of the current status of the use of hormonal drugs for the major hormone-dependent diseases. Further, it aims to explain the mechanisms behind the -sometimes- observed weak effects and low therapeutic efficacy of these drugs and the possibilities and the advantages of combined treatments targeting several enzymes in the local estrogen formation, or drugs acting with different therapeutic mechanisms.

We study a family of McKean-Vlasov (mean-field) type ergodic optimal control problems with linear control, and quadratic dependence on control of the cost function. For this class of problems we establish existence and uniqueness of an optimal control. We propose an $N$-particles Markovian optimal control problem approximating the McKean-Vlasov one and we prove the convergence in relative entropy, total variation and Wasserstein distance of the law of the former to the law of the latter when $N$ goes to infinity. Some McKean-Vlasov optimal control problems with singular cost function and the relation of these problems with the mathematical theory of Bose-Einstein condensation is also established., Introduction has been modified. New references have been added. Small errors and typos have been corrected

IntroductionEndometrial cancer (EC) is the most common gynecological cancer with a rising incidence, attributed to advanced life expectancy and obesity. Adipose tissue (AT) is an important endocrine organ, and its metabolic activity is affected by the different anatomical distribution or locations. AT distribution influences a number of diseases. In EC, it remains unclear whether the type of AT distribution affects development or prognosis. This systematic review aimed to determine whether AT distribution is associated with patient characteristics, disease characteristics, and patient prognosis in EC.Materials and methodsA search was conducted in Medline, MEDLINE EMBASE, and Cochrane Library. We included studies that enrolled patients with EC with any histological subtype and that distinguished between the visceral and subcutaneous AT compartment. In eligible studies, correlative analyses were performed for all outcome measures and AT distribution.ResultsEleven retrospective studies were included, with a wide range of measurements for the visceral and subcutaneous AT compartments. AT distribution was found to be significantly correlated to a number of relevant (disease) characteristics including obesity measures, histological subtype, lymph node metastasis, and sex steroid levels. Five studies reported on survival parameters including overall survival, progression-free survival and disease-specific survival, and they found that increased VAT volume was statistically significantly associated with a worse survival.Discussion/conclusionThis review demonstrates that there are significant correlations between AT distribution and prognosis, body mass index, sex steroid levels, and disease characteristics like histology. Well-designed, prospective, and larger-scale studies are needed to pinpoint these differences more specifically and understand how it can add in prediction and even therapy in EC.

Supplemental material, sj-pdf-2-msj-10.1177_13524585211040222 for ADEM after ChAdOx1 nCoV-19 vaccine: A case report by Virginia Rinaldi, Gianmarco Bellucci, Andrea Romano, Alessandro Bozzao and Marco Salvetti in Multiple Sclerosis Journal

Supplemental material, sj-pdf-1-msj-10.1177_13524585211040222 for ADEM after ChAdOx1 nCoV-19 vaccine: A case report by Virginia Rinaldi, Gianmarco Bellucci, Andrea Romano, Alessandro Bozzao and Marco Salvetti in Multiple Sclerosis Journal

Previous research is expanded, having as an objective a different measurement, focusing on what immediate changes occur after the application of the laryngeal massage technique in patients with muscle- tension dysphonia type I and II. The calculation of values of integrated indices of ANAGRAF software was used: Integrated disturbance index (IPI), Articulatory speech precision index (IPA) and the efficient use of energy index. The IPI, linked with both glottal and vocal tract alterations in the glottal source showed significant changes in values pre -post application of the technique. The jitter and harmonic/noise values were the largest contributors in the IPI decrease. Se amplían investigaciones precedentes, objetivando con nuevas mediciones, qué cambios inmediatos se producen, luego de la aplicación de la técnica de masaje laríngeo, en sujetos con disfonías músculotensional tipo I y II. Se utilizó el cálculo de valores de índices integrados del software ANAGRAF: Índice de perturbación integrado (IPI), Índice de precisión vocal articulatoria (IPA) y el Índice de aprovechamiento de la energía (IAE). El IPI, vinculado con alteraciones vocales en la fuente glotal (jitter y shimmer) y con alteraciones en el tracto vocal (relación armónico/ruido y amplitud del cepstrum), mostró cambios significativos en los valores pre-post aplicación de la técnica. El jitter y armónico/ruido fueron los valores que más contribuyeron en la disminución del IPI.

Magnetic resonance imaging (MRI) with a dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI) sequence to study brain tumours provides information on the haemodynamic characteristics of the neoplastic tissue. Brain perfusion maps and calculation of perfusion parameters, such as relative cerebral blood flow (rCBF), relative cerebral blood volume (rCBV) and mean transit time (MTT) allow assessment of vascularity and angiogenesis within tumours of the central nervous system (CNS), thus providing additional information to conventional MRI sequences. Although DSC-PWI has long been used, its clinical use in the study of brain tumours in daily clinical practice is still to be defined. The aim of this review was to analyse the application of perfusion MRI in the study of brain tumours by summarising our personal experience and the main results reported in the literature.

Purpose To investigate the local control and radiation-induced brain necrosis in patients with brain metastases >2 cm in size who received single-fraction or multifraction stereotactic radiosurgery (SRS); factors associated with clinical outcomes and the development of brain radionecrosis were assessed. Methods and Materials Two hundred eighty-nine consecutive patients with brain metastases >2.0 cm who received SRS as primary treatment at Sant'Andrea Hospital, University of Rome Sapienza, Rome, Italy, were analyzed. Cumulative incidence analysis was used to compare local control and radiation-induced brain necrosis between groups from the time of SRS. To achieve a balanced distribution of baseline covariates between treatment groups, a propensity score analysis was used. Results The 1-year cumulative local control rates were 77% in the single-fraction SRS (SF-SRS) group and 91% in the multifraction SRS (MF-SRS) group ( P =.01). Recurrences occurred in 25 and 11 patients who received SF-SRS or MF-SRS ( P =.03), respectively. Thirty-one patients (20%) undergoing SF-SRS and 11 (8%) subjected to MF-SRS experienced brain radionecrosis ( P =.004); the 1-year cumulative incidence rate of radionecrosis was 18% and 9% ( P =.01), respectively. Significant differences between the 2 groups in terms of local control and risk of radionecrosis were maintained after propensity score adjustment. Conclusions Multifraction SRS at a dose of 27 Gy in 3 daily fractions seems to be an effective treatment modality for large brain metastases, associated with better local control and a reduced risk of radiation-induced radionecrosis as compared with SF-SRS.

Primer sequences for quantitative real-time-PCR. Sequences of primers (5′-3′) used for quantitative real-time-PCR including length of PCR product and annealing temperature. bp base pair; Fwd Forward; Rev Reverse. (DOC 48 kb)

Angiolipomas are benign mesenchymal tumors infrequently affecting the head and neck region, manifesting themselves as small (

Trabajo presentado en el 18ème colloque du Club des Bactéries Lactiques, celebrado en Clermont-Ferrand (Francia) del 22 al 24 de mayo de 2012.

International audience; AIMS: Lactobacillus brevis IOEB 9809 is able to produce both tyramine and putrescine via tyrosine decarboxylase and agmatine deiminase enzymes, respectively, when cultured on synthetic media. The aims of this study were to assess the expression of L. brevis IOEB 9809 tdc and aguA1 genes, during wine fermentation and to evaluate the effect of substrate availability and pH on tdc and aguA1 expression, as well as on biogenic amine production and L. brevis viability. METHODS AND RESULTS: The relative expression of L. brevis IOEB 9809 tdc and aguA1 genes was analysed in wine by quantitative real-time RT-PCR (qRT-PCR) during a period of incubation of 30 days. Cell viability, pH values, putrescine and tyramine concentration were monitored throughout the experiments. CONCLUSIONS: The wine trials indicated that L. brevis IOEB 9809 is able to produce both tyramine and putrescine during wine fermentation. Increased cell viability was also observed in wine supplemented with tyrosine or agmatine. qRT-PCR analysis suggests a strong influence of substrate availability on the expression of genes coding for tyrosine decarboxylase and agmatine deiminase in L. brevis IOEB 9809. Less evident is the relationship between putrescine and tyramine production and tolerance to wine pH. SIGNIFICANCE AND IMPACT OF STUDY: To our knowledge, this study represents the first assessment of relative expression of L. brevis IOEB 9809 genes involved in biogenic amine production in wine. Furthermore, an effect of biogenic amine production on viability of L. brevis during wine fermentation was established.

The present invention relates to a single-mode external-cavity tuneable laser including a gain medium, a tuneable element and a channel allocation grid element. The channel allocation grid element is preferably a FP etalon, which is structured and configured to define a plurality of equally spaced transmission peaks corresponding to the ITU channel grid, e.g., 200, 100, 50 or 25 GHz. The tuneable element, preferably a tuneable mirror, serves as the coarse tuning element that discriminates between the peaks of the grid etalon. The tuneable laser of the invention has a relatively short cavity length of not more than 15 mm, preferably not larger than 12 mm. It has been found that the FP etalon introduces a phase non-linearity in the external cavity, which induces a compression of the cavity modes, i.e., a reduction in the cavity mode spacing, in correspondence to the etalon transmission peaks. Mode compression increases with the decrease of the FWHM bandwidth of the grid FP etalon, hereafter referred to as (FWHM)FP. (FWHM)FP should be comprised in the range from about 2 GHz to about 8 GHz. Preferably, (FWHM)FP is comprised between approximately 3 and 6 GHz.

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Treballs Finals de Grau de Dret. Universitat de Barcelona. Curs: 2021-2022. Tutor: Romano, Andrea, Vivimos en un mundo globalizado donde se producen constantes movimientos migratorios. Las personas extranjeras que se establecen en España normalmente es por causas socioeconómicas y, por este motivo, pretenden encontrar un futuro con mejores oportunidades laborales. Las personas migrantes pueden residir en España con una autorización administrativa de residencia y trabajo, sin esta autorización o con una autorización no renovada. En estos dos últimos supuestos, la persona extranjera se encontrará en una situación administrativa irregular y, por este motivo, una posible vía para la regularización de su situación administrativa irregular será la autorización de residencia temporal por circunstancias excepcionales por razón de arraigo. El presente trabajo, después de abordar un breve análisis sobre los diferentes tipos de arraigo, se centrará en el estudio del arraigo laboral (concepto, requisitos, procedimiento y sujetos que pueden solicitarlo), que solo se concederá si se acreditan los requisitos establecidos legalmente en la Ley Orgánica 4/2000, de 11 de enero, sobre derechos y libertades de los extranjeros en España y su integración social y en el Real Decreto 557/2011, de 20 de abril, por el que se aprueba el Reglamento de la Ley Orgánica 4/2000, sobre derechos y libertades de los extranjeros en España y su integración social, tras su reforma por Ley Orgánica 2/2009, junto con lo establecido en la Instrucción SEM 1/2021 sobre el procedimiento relativo a las autorizaciones de residencia temporal por razones de arraigo laboral y la reciente jurisprudencia del Tribunal Supremo del año 2021 en esta materia.

A numerical model of cryo-maceration plant for mashed grapes has been realized to simulate the rapid cooling process for mashed grapes according to the number of nozzles enabled to inject CO2, to their flow and temperature of CO2 injected. ANSYS CFX program was used and two geometries have been considered with the axis of each nozzle orthogonal and parallel to the flow direction. Different boundary conditions have been considered. For the models have been considered the most burdensome condition.

Bladder cancer is the 9th most common tumour worldwide with Urothelial Carcinoma (UC) being the most frequent type of the disease. Cisplatin-based chemotherapy is the standard of care in advanced and metastatic UC. However, its therapeutic efficacy is limited by chemoresistance. Cisplatin-resistant UC cell lines were generated to investigate underlying mechanisms and to develop new approaches for overcoming resistance. Interestingly, each cisplatin-resistant cell line contained an individual assortment of resistance mechanisms at multiple levels. This heterogeneity among several cell lines of the same tumour entity may be responsible for the complicated scenario, which can be observed in the clinic.

In the UK 13000 people are diagnosed with oesophageal and gastric cancer annually. Despite improvements in surgical and oncological treatment of oesophageal and gastric cancer 5-year survival remains poor at 10-30%. At the present time only one third of patients with oesophago-gastric cancer are managed on a curative treatment pathway due to the fact that most cancers are at an advanced stage by the time of diagnosis. There is a clear need for a non-invasive test to diagnose oesophago-gastric cancer at the earliest possible stage. Previous studies have highlighted potential volatile organic compound (VOC) biomarkers present in the exhaled breath of patients with oesophago-gastric cancer which could be used in future to develop a non-invasive diagnostic test. The primary aim of this thesis was to address the barriers to scaling exhaled breath testing for VOCs into clinical practice. A high throughput exhaled breath collection system has been developed to enable large scale multi-centre studies to be performed. The impact of potential confounding factors on breath testing for oesophago-gastric cancer have been assessed, potential new biomarkers have been identified and a quality control system to be used in future studies has been developed with the ultimate aim of validating a breath test for oesophago-gastric cancer in clinical practice. Open Access

Tesis doctoral inédita. Universidad Autónoma de Madrid, Facultad de Derecho. Departamento de Derecho Privado, Social y Económico

Executive functions (EFs) allow to planning and voluntarily and autonomously produce targeted behaviors, in unusual or complex conditions in which the automated response schemes are not appropriate or sufficient to achieve behavior goal. The aim of this study was to evaluate EFs in preschool children presenting with Global Developmental Delay (GDD). Fifty-two preschool children participated in this study: 20 GDD children and 32 typical developing children (TDC) as control group, enrolled in the schools of Campania and Sicily Regions. All subjects underwent evaluation of the executive functioning through the administration of the Battery for the Assessment of Preschool Executive Functions (BAFE) and the Behavior Rating of Executive Function-Preschool Version (BRIEF-P). The two groups were comparable for age and gender. GDD children showed significantly lower scores in all BAFE subscales and significantly higher in all BRIEF-P subscales compared to TDC controls. EFs are integrated with each other and as many functions are the essential basis for the other basic skills as well as basis for more complex cognitive skills. During childhood, EFs' difficulties tend to influence not just a single area/expertise but have a global impact that extends to management, development, planning and daily living.