Effects of a selective cyclooxygenase-2 inhibitor on endometrial epithelial cells from patients with endometriosis

Celecoxib, a selective cyclooxygenase (COX)-2 inhibitor, also has anti-proliferative properties and pro-apoptotic effects on different in vivo and in vitro models, two actions that may be efficacious in therapy for endometriosis. We evaluated the effects of celecoxib on apoptosis and proliferation, and vascular endothelial growth factor (VEGF) production and COX-2 expression and activity in endometrial epithelial cells (EECs).Fil: Olivares, Carla Noemi. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Bilotas, Mariela Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Buque, Ricardo. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Borghi, Mario. Centro de Estudios en Ginecología y Reproducción; ArgentinaFil: Sueldo, Carlos. Centro de Estudios en Ginecología y Reproducción; ArgentinaFil: Tesone, Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Meresman, Gabriela Fabiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentin

Smart-working VS office work: how does personal exposure to different air pollutants change?

The COVID-19 pandemic is raging all over the world, with possible structural effects on the work: the smart-working (WFH -Working From Home) role is therefore emphasized by the fact that it could become a traditional way of working in many work sectors. Several scientific papers have recently analyzed the WFH phenomenon under different aspects, but scientific studies have not yet been conducted considering the differences between WFH and WFO (Working From Office), in terms of evaluation of personal exposure assessment to selected airborne pollutants. This study, therefore, aims to evaluate, using portable monitors, the differences in terms of personal exposure to selected airborne pollutants, during different working conditions (WFO vs WFH), over long periods of time (from days to weeks), extending the results to even longer periods (years), to adhere to the approach proposed by the concept of the exposome. The preliminary results of this study refer to three separate phases of the work (i) re-analyses of literature data via Monte Carlo simulation, and assessment of personal exposure to different air pollutants during different working conditions, during (ii) “long term” campaign and (iii) a “short term” monitoring campaign. During the two different measurement campaigns, portable instrumentation was used, because of the ability of these kinds of instruments to obtain data characterized by a high spatial and temperature resolution. The re-elaborations of the data obtained from the literature show how, under different conditions, the exposure concentrations to different PM fractions are statistically lower in WFH working conditions, compared to WFO conditions. These results are in contrast with the preliminary results obtained from exploratory monitoring (both for the “long term” and for the “short term” campaigns). The results obtained from these exploratory monitoring show that the WFH condition has a greater impact on the daily exposure of the monitored subjects, compared to the WFO condition

Monitor and sensors 2.0 for exposure assessment to airborne pollutants

In recent years, the issue of exposure assessment to airborne pollutants has become increasingly popular, both in the occupational and environmental fields. The increasingly stringent national and international air quality standards and exposure limit values both for indoor environments and occupational exposure limit values have been developed with the aim of protecting the health of the general population and workers. On the other hand, this requires a considerable and continuous development of the technologies used to monitor the concentrations of the pollutants to ensure the reliability of the exposure assessment studies. In this regard, one of the most interesting aspects is certainly the development of “new generation” instrumentation for monitoring airborne pollutants (“Next Generation Monitors and Sensors” – NGMS). The main purpose of this work is to analyze the state of the art regarding the afore-mentioned instrumentation, to be able to investigate any practical applications within exposure assessment studies. In this regard, a systematic review of the scientific literature was carried out using three different databases (Scopus, PubMed and Web of Knowledge) and the results were analyzed in terms of the objectives set out above. What emerged is the fact that the use of NGMSs is increasingly growing within the scientific community for exposure assessment studies applied to the occupational and environmental context. The investigated studies have emphasized that NGMSs cannot be considered, in terms of the reliability of the results, to be equal to the reference measurement tools and techniques (i.e., those defined in recognized methods used for regulatory purposes), but they can certainly be integrated into the internal exposure assessment studies to improve their spatial-temporal resolution. These tools have the potential to be easily adapted to different types of studies, are characterized by a small size, which allows them to be worn comfortably without affecting the normal activities of workers or citizens, and by a relatively low cost. Despite this, there is certainly a gap with respect to the reference instrumentation, regarding the measurement performance and quality of the data provided; the objective to be set, however, is not to replace the traditional instrumentation with NGMSs but to integrate and combine the two typologies of instruments to benefit from the strengths of both, therefore, the desirable future developments in this sense has been discussed in this work

Interacción de dos hongos toxicogénicos con una cepa de Streptomyces sobre el desarrollo de plantas de trigo

Entre los microorganismos antagonistas de los suelos donde se cultivan cereales se hallan Streptomyces capaces de producir sustancias inhibidoras que pueden afectar la viabilidad y capacidad de diseminación de distintas especies de Aspergillus Y Fusarium y su capacidad para producir aflatoxinas y trichotecenos.El objetivo del presente estudio fue evaluar el efecto de la interacción entre hongos toxicogénicos (Aspergillus parasiticus y Fusarium tricinctum NRRL 3299) Y Streptomyces sp.antagónicos del crecimiento de tales hongos sobre el desarrollo de plantas de trigo.Se realizaron las siguientes actividades: a) inoculación de semillas de trigo, con el Streptomyces inhibidor, b) estudio del poder germinativo de las semillas de trigo, c)cultivo en cámara invernáculo de semillas inoculadas y sin inocular sembradas en tierras con y sin los hongos toxicogénicos, d) comprobación de la invasividad o ataque de los hongos mediante el rociado de espigas de plantas provenientes de suelos infectados con una suspensión de conidios de los hongos infectantes,e) determinación de las variaciones en las características botánicasde las plantas de trigo.Se pudo concluir que: 1) la presencia de hongos toxicogénicos no alteró el poder gemtinativo de las semillas de trigo, 2) el desarrollo vegetal, número y peso promedio de los granos de las plantas provenientes desuelos infectados con los hongos toxicogénicos fué significativamentemayor al de las plntas crecidas en tierra esteril,  3) el estudio anatómico de las plantas no puso en evidencia invasión o ataque por parte de los hongos

Discovery of a Potent Dual Inhibitor of Aromatase and Aldosterone Synthase.

Estrogen deficiency derived from inhibition of estrogen biosynthesis is a typical condition of postmenopausal women and breast cancer (BCs) patients undergoing antihormone therapy. The ensuing increase in aldosterone levels is considered to be the major cause for cardiovascular diseases (CVDs) affecting these patients. Since estrogen biosynthesis is regulated by aromatase (CYP19A1), and aldosterone biosynthesis is modulated by aldosterone synthase (CYP11B2), a dual inhibitor would allow the treatment of BC while reducing the cardiovascular risks typical of these patients. Moreover, this strategy would help overcome some of the disadvantages often observed in single-target or combination therapies. Following an in-depth analysis of a library of synthesized benzylimidazole derivatives, compound was found to be a potent and selective dual inhibitor of aromatase and aldosterone synthase, with IC values of 2.3 and 29 nM, respectively. Remarkably, the compound showed high selectivity with respect to 11β-hydroxylase (CYP11B1), as well as CYP3A4 and CYP1A2. When tested in cells, showed potent antiproliferative activity against BC cell lines, particularly against the ER+ MCF-7 cells (IC of 0.26 ± 0.03 μM at 72 h), and a remarkable pro-apoptotic effect. In addition, the compound significantly inhibited mTOR phosphorylation at its IC concentration, thereby negatively modulating the PI3K/Akt/mTOR axis, which represents an escape for the dependency from ER signaling in BC cells. The compound was further investigated for cytotoxicity on normal cells and potential cardiotoxicity against ERG and Nav1.5 ion channels, demonstrating a safe biological profile. Overall, these assays demonstrated that the compound is potent and safe, thus constituting an excellent candidate for further evaluation. [Abstract copyright: © 2023 The Authors. Published by American Chemical Society.

Novel P-in-N Si-Sensor technology for high resolution and high repetition-rate experiments at accelerator facilities

Linear array detectors with high spatial resolution and MHz frame-rates are essential for high-rate experiments at accelerator facilities. KALYPSO, a line array detector with 1024 pixels operating over 1 Mfps has been developed. To improve the spatial resolution and sensitivity at different wavelengths, novel p-in-n Si microstrip sensors based on have been developed with a pitch of 25 micrometer. The efficiency of the sensor has been improved with the use of anti reflecting coating layers optimized for near infrared, visible and near ultraviolet. In this contribution the detector system and the sensors will be presented

Functional reconstitution of HBV-specific CD8 T cells by in vitro polyphenol treatment in chronic hepatitis B.

Background & aims In chronic HBV infection, mitochondrial functions and proteostasis are dysregulated in exhausted HBV-specific CD8 T cells. To better characterise the potential involvement of deregulated protein degradation mechanisms in T cell exhaustion, we analysed lysosome-mediated autophagy in HBV-specific CD8 T cells. Bioactive compounds able to simultaneously target both mitochondrial functions and proteostasis were tested to identify optimal combination strategies to reconstitute efficient antiviral CD8 T cell responses in patients with chronic HBV infection. Methods Lysosome-mediated degradation pathways were analysed by flow cytometry in virus-specific CD8 T cells from patients with chronic HBV infection. Mitochondrial function, intracellular proteostasis, and cytokine production were evaluated in HBV-peptide-stimulated T cell cultures, in the presence or absence of the polyphenols resveratrol (RSV) and oleuropein (OLE) and their metabolites, either alone or in combination with other bioactive compounds. Results HBV-specific CD8 T cells from patients with CHB showed impaired autophagic flux. RSV and OLE elicited a significant improvement in mitochondrial, proteostasis and antiviral functions in CD8 T cells. Cytokine production was also enhanced by synthetic metabolites, which correspond to those generated by RSV and OLE metabolism in vivo, suggesting that these polyphenols may also display an effect after transformation in vivo. Moreover, polyphenolic compounds improved the T cell revitalising effect of mitochondria-targeted antioxidants and of programmed cell death protein 1/programmed cell death ligand 1 blockade. Conclusions Simultaneously targeting multiple altered intracellular pathways with the combination of mitochondria-targeted antioxidants and natural polyphenols may represent a promising immune reconstitution strategy for the treatment of chronic HBV infection. Lay summary In chronic hepatitis B, antiviral T lymphocytes are deeply impaired, with many altered intracellular functions. In vitro exposure to polyphenols, such as resveratrol and oleuropein, can correct some of the deregulated intracellular pathways and improve antiviral T cell function. This effect can be further strengthened by the association of polyphenols with antioxidant compounds in a significant proportion of patients. Thus, the combination of antioxidants and natural polyphenols represents a promising strategy for chronic hepatitis B therapy

Smart working in Italy: what aspects to consider in terms of health prevention and protection?

Agile (or remote) work has spread since the early 90s, but the adoption of this type of work hasn’t always been exploit ed to its full potential. Recently, this way of working has acquired greater importance: in response to the COVID-19 pandemic, to limit the number of infections, and consequent number of deaths and hospital admissions, many coun tries have adopted a wide spectrum of containment measures, such as encouraging (or oblige) people to work remote ly, whenever possible. Due to this containment measure, millions of workers around the world have been destined to work from home. Moreover, it would seem that this mode of working will stand out as a hybrid mode form, to ensure a better balance between office- and home-working. For this reason, the present work aims to highlight the main out comes from studies conducted in Italy, concerning the positive and negative effects of smart working, reporting the gaps relating to the assessments of the remote working environment. To achieve this goal, results (N: 9 scientific papers) obtained from a search query set for extraction of studies from a scientific literature database were analyzed. In addition to report the positive and negative effects of smart working, our research shows that the studies conducted in Italy regarding this way of working are still scarce and based only on the administration of a questionnaire (or on the conduction of an interview) to workers. No real assessments have been performed, in terms of workers’ safety and health, in the condition of working from home. An in depth analysis of the experience of employees involved in remote working conditions could be of particular interest in future studies, to maximize the positive aspects and reduce the risks of worsening the physical and psy chosocial well-being of employees. In fact, if smart working would become a common way of working as reported in the literature, it could have a significant impact on both organizations and employees and it should therefore be investigated in the best possible wa

Clinical and epidemiological profile of patients with mental disorders in a specialized outpatient clinic and its role in the psychosocial care network

IntroductionMental health disorders (MHDs) are responsible for much impairment of quality of life in Brazil and worldwide. Early diagnosis and effective treatment strategies are required due to the heterogeneous symptoms and multifactorial etiology.MethodsA descriptive retrospective observational study was performed aiming to characterize the clinical and psychiatric profiles of patients with MHD attending a Brazilian public tertiary psychiatric outpatient clinic, which is a reference health service for more than 2 million inhabitants. Predominant clinical and sociodemographic aspects of patients were evaluated between March 2019 and March 2021.ResultsA total of 8,384 appointments were analyzed. The majority of patients were female, and the mean age was 45 years old. Generalized anxiety disorder (GAD) was the most common MHD. The prevailing symptoms were sadness, anxiety, and irritability, with the most prescribed medications being selective serotonin reuptake inhibitors.ConclusionThe epidemiological characterization of mental disorders in specialized mental health outpatient clinics provides evidence for the establishment of more specific protocols and advocates a dimensional transdiagnostic approach as an aid to public mental health services

A new molecular classification to drive precision treatment strategies in primary Sjögren’s syndrome

There is currently no approved treatment for primary Sjögren's syndrome, a disease that primarily affects adult women. The difficulty in developing effective therapies is -in part- because of the heterogeneity in the clinical manifestation and pathophysiology of the disease. Finding common molecular signatures among patient subgroups could improve our understanding of disease etiology, and facilitate the development of targeted therapeutics. Here, we report, in a cross-sectional cohort, a molecular classification scheme for Sjögren's syndrome patients based on the multi-omic profiling of whole blood samples from a European cohort of over 300 patients, and a similar number of age and gender-matched healthy volunteers. Using transcriptomic, genomic, epigenetic, cytokine expression and flow cytometry data, combined with clinical parameters, we identify four groups of patients with distinct patterns of immune dysregulation. The biomarkers we identify can be used by machine learning classifiers to sort future patients into subgroups, allowing the re-evaluation of response to treatments in clinical trials