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  • Spencer Hougaard posted an update 22 days ago

    Signaling mediated by cytokines and chemokines is involved in glaucoma-associated neuroinflammation and in the damage of retinal ganglion cells (RGCs). Using multiplexed immunoassay and immunohistochemical techniques in a glaucoma mouse model at different time points after ocular hypertension (OHT), we analyzed (i) the expression of pro-inflammatory cytokines, anti-inflammatory cytokines, BDNF, VEGF, and fractalkine; and (ii) the number of Brn3a+ RGCs. In OHT eyes, there was an upregulation of (i) IFN-γ at days 3, 5, and 15; (ii) IL-4 at days 1, 3, 5, and 7 and IL-10 at days 3 and 5 (coinciding with downregulation of IL1-β at days 1, 5, and 7); (iii) IL-6 at days 1, 3, and 5; (iv) fractalkine and VEGF at day 1; and (v) BDNF at days 1, 3, 7, and 15. In contralateral eyes, there were (i) an upregulation of IL-1β at days 1 and 3 and a downregulation at day 7, coinciding with the downregulation of IL4 at days 3 and 5 and the upregulation at day 7; (ii) an upregulation of IL-6 at days 1, 5, and 7 and a downregulation at 15 days; (iii) an upregulation of IL-10 at days 3 and 7; and (iv) an upregulation of IL-17 at day 15. In OHT eyes, there was a reduction in the Brn3a+ RGCs number at days 3, 5, 7, and 15. OHT changes cytokine levels in both OHT and contralateral eyes at different time points after OHT induction, confirming the immune system involvement in glaucomatous neurodegeneration.(1) Background Cyberbullying is a social concern in adolescents. The practice of physical activity is a key factor in protection against cyberbullying related to the multiple psychological benefits. learn more Therefore, the study sets out to analyse the relationship between amount, types, enjoyment of physical activity and performance in physical education with cyberbullying. (2) Methods A sample of 867 adolescents between 12 and 19 years of age from two schools in Andalusia (Spain) was studied. A computer-based questionnaire given in the classroom was used, with two questions about the type of physical activity, one on physical education performance, the Scale of Enjoyment of Physical Activity (PACES) and the Spanish version of the European Cyberbullying Intervention Project Questionnaire (ECIPQ). (3) Results Clear relationships were found between the practice of physical activity and cybervictimisation. However, less involvement has been observed among girls who practice physical activity in cyberaggression. (4) Conclusions In relation to the types of physical activity, it seems that practising physical activities that involve competition can help to develop defence mechanisms against cyberaggression, as well as improve values to be less involved in cyberaggression.Computer aided drug-design methods proved to be powerful tools for the identification of new therapeutic agents. We employed a structure-based workflow to identify new inhibitors targeting mTOR kinase at rapamycin binding site. By combining molecular dynamics (MD) simulation and pharmacophore modelling, a simplified structure-based pharmacophore hypothesis was built starting from the FKBP12-rapamycin-FRB ternary complex retrieved from RCSB Protein Data Bank (PDB code 1FAP). Then, the obtained model was used as filter to screen the ZINC biogenic compounds library, containing molecules derived from natural sources or natural-inspired compounds. The resulting hits were clustered according to their similarity; moreover, compounds showing the highest pharmacophore fit-score were chosen from each cluster. The selected molecules were subjected to docking studies to clarify their putative binding mode. The binding free energy of the obtained complexes was calculated by MM/GBSA method and the hits characterized by the lowest ΔGbind values were identified as potential mTOR inhibitors. Furthermore, the stability of the resulting complexes was studied by means of MD simulation which revealed that the selected compounds were able to form a stable ternary complex with FKBP12 and FRB domain, thus underlining their potential ability to inhibit mTOR with a rapamycin-like mechanism.In Spain, there has been a progressive increase in aging. Specifically, Leon has been one of the Spanish provinces with the highest aging index. Polypharmacy is highly prevalent among the elderly, with significant consequences for safety. The aim of this study was to assess the consumption of drugs in a nursing home in the province of Leon and establish the relationship between polypharmacy and the most common comorbid diseases. A descriptive, observational, and cross-sectional study design was used. Residents’ information and treatments were collected by reviewing on medical charts, completed with clinical information obtained from the physician of the nursing home. The mean age of residents was 86.8 years, and 63.8% were female. Mean medical consumption amounted to 7.02 prescriptions. Polypharmacy was observed in 54.9% of residents, and excessive polypharmacy in 22.1%. The most commonly used medications (ATC classification) were those acting on the cardiovascular system (84.4%) and the nervous system (82.8%). A high-level of drug consumption was observed in the nursing home. Interventions should focus on those residents hospitalized the last year and with recent contact with a general practitioner. There is a need to develop a comprehensive monitoring system to assess the quality of prescriptions for nursing home residents.Nosocomial infections (NIs) pose an increasing threat to public health. The majority of NIs are bacterial, fungal, and viral infections; however, parasites also play a considerable role in NIs, particularly in our increasingly complex healthcare environment with a growing proportion of immunocompromised patients. Moreover, parasitic infections acquired via blood transfusion or organ transplantation are more likely to have severe or fatal disease outcomes compared with the normal route of infection. Many of these infections are preventable and most are treatable, but as the awareness for parasitic NIs is low, diagnosis and treatment are often delayed, resulting not only in higher health care costs but, importantly, also in prolonged courses of disease for the patients. For this article, we searched online databases and printed literature to give an overview of the causative agents of parasitic NIs, including the possible routes of infection and the diseases caused. Our review covers a broad spectrum of cases, ranging from widely known parasitic NIs, like blood transfusion malaria or water-borne cryptosporidiosis, to less well-known NIs, such as the transmission of Strongyloides stercoralis by solid organ transplantation or nosocomial myiasis.

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