88 research outputs found

    The central nervous system source modulates microglia function and morphology in vitro

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    The regional heterogeneity of microglia was first described a century ago by Pio del Rio Hortega. Currently, new information on microglia heterogeneity throughout central nervous system (CNS) regions is being revealed by high-throughput techniques. It remains unclear whether these spatial specificities translate into different microglial behaviors in vitro. We cultured microglia isolated from the cortex and spinal cord and analyzed the effect of the CNS spatial source on behavior in vitro by applying the same experimental protocol and culture conditions. We analyzed the microglial cell numbers, function, and morphology and found a distinctive in vitro phenotype. We found that microglia were present in higher numbers in the spinal-cord-derived glial cultures, presenting different expressions of inflammatory genes and a lower phagocytosis rate under basal conditions or after activation with LPS and IFN-γ. Morphologically, the cortical microglial cells were more complex and presented longer ramifications, which were also observed in vivo in CX3CR1+/GFP transgenic reporter mice. Collectively, our data demonstrated that microglial behavior in vitro is defined according to specific spatial characteristics acquired by the tissue. Thus, our study highlights the importance of microglia as a source of CNS for in vitro studies.This work was funded by the Santa Casa Neuroscience Awards—Prize Melo e Castro for Spinal Cord Injury Research (MC-18-2021), and it was partially funded by the Wings for Life Spinal Cord Research Foundation (WFL-ES-03/19). This work was also funded by national funds through the Foundation for Science and Technology (FCT)—projects UIDB/50026/2020, UIDP/50026/2020, and EXPL/MED-PAT/0931/2021, and by the project NORTE-01-0145-FEDER-000039, supported by the Norte Portugal Regional Operational Programme (NORTE 2020) under the PORTUGAL 2020 Partnership Agreement through the European Regional Development Fund (ERDF). We would like to acknowledge the support given by the Portuguese Foundation of Science and Technology to AGP (2020.07534.BD), AM (UMINHO/BIL-CNCG/2022/16), SM (CEECIND/01902/2017), and NAS (CEECIND/04794/2007)

    Tricritical behaviour in deterministic aperiodic Ising systems

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    We use a mixed-spin model, with aperiodic ferromagnetic exchange interactions and crystalline fields, to investigate the effects of deterministic geometric fluctuations on first-order transitions and tricritical phenomena. The interactions and the crystal field parameters are distributed according to some two-letter substitution rules. From a Migdal-Kadanoff real-space renormalization-group calculation, which turns out to be exact on a suitable hierarchical lattice, we show that the effects of aperiodicity are qualitatively similar for tricritical and simple critical behaviour. In particular, the fixed point associated with tricritical behaviour becomes fully unstable beyond a certain threshold dimension (which depends on the aperiodicity), and is replaced by a two-cycle that controls a weakened and temperature-depressed tricritical singularity.Comment: Formatting improved. 7 pages, 2 figures (included). Journal reference adde

    Anthracyclines versus No Anthracyclines in the Neoadjuvant Strategy for HER2+ Breast Cancer: Real-World Evidence

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    Background and Objectives Deescalation strategies omitting anthracyclines (AC) have been explored in early human epidermal growth factor receptor 2-positive breast cancer (HER2+ EBC), showing similar efficacy regarding pathological complete response (pCR) and long-term outcomes as AC-containing regimens. The standard treatment for this tumor subtype is based on chemotherapy and dual HER2 blockade with trastuzumab and pertuzumab, with AC-containing regimens remaining a frequent option for these patients, even in non-high-risk cases. The primary aim of this study was to assess and compare the effectiveness of neoadjuvant regimens with and without AC used in the treatment of HER2+ EBC in the clinical practice according to the pCR achieved with each. Methods This retrospective multicentric study included patients with HER2+ EBC from Portuguese, Spanish, and Chilean hospitals (January 2018–December 2021). Patients receiving neoadjuvant therapy (NAT) with dual HER2 blockade (trastuzumab and pertuzumab), followed by surgery, were included. Statistical analysis used chi-squared/Fisher’s exact test for associations, multivariate logistic regression for pCR, and Kaplan–Meier method for event-free survival (EFS). IBM SPSS Statistics 29.0 analyzed the data. Results The study included 371 patients from eight hospitals. Among them, 237 received sequential AC and taxane-based chemotherapy with 4 cycles of trastuzumab and pertuzumab, while 134 received 6 cycles of TCHP (docetaxel, carboplatinum, trastuzumab, and pertuzumab). The average age of the patients was 52.8 years and 52.7 years, respectively. Omitting AC from the neoadjuvant approach did not preclude achieving pCR [p = 0.246, 95% confidence interval (CI) 0.235–0.257] and was safe regardless of patient characteristics. Relapse rates were 6.8% (16 patients) in the AC group and 4.5% (6 patients) in the TCHP group. Over a median follow-up of 2.9 years, the estimated 3-year EFS was 92.5% in the AC group and 95.4% in the TCHP group (hazard ratio 0.602, 95% CI 0.234–1.547, p = 0.292, favoring TCHP). Conclusion This study reports real-world evidence showing similar pCR and EFS outcomes with treatment regimens with and without AC and raises awareness of possible overtreatment and long-term toxicity in some patients with HER2+ EBC with the use of AC

    Importation and early local transmission of COVID-19 in Brazil, 2020

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    We conducted the genome sequencing and analysis of the first confirmed COVID-19 infections in Brazil. Rapid sequencing coupled with phylogenetic analyses in the context of travel history corroborate multiple independent importations from Italy and local spread during the initial stage of COVID-19 transmission in Brazil

    HIV-1-Transmitted Drug Resistance and Transmission Clusters in Newly Diagnosed Patients in Portugal Between 2014 and 2019

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    Objective: To describe and analyze transmitted drug resistance (TDR) between 2014 and 2019 in newly infected patients with HIV-1 in Portugal and to characterize its transmission networks. Methods: Clinical, socioepidemiological, and risk behavior data were collected from 820 newly diagnosed patients in Portugal between September 2014 and December 2019. The sequences obtained from drug resistance testing were used for subtyping, TDR determination, and transmission cluster (TC) analyses. Results: In Portugal, the overall prevalence of TDR between 2014 and 2019 was 11.0%. TDR presented a decreasing trend from 16.7% in 2014 to 9.2% in 2016 (p for-trend = 0.114). Multivariate analysis indicated that TDR was significantly associated with transmission route (MSM presented a lower probability of presenting TDR when compared to heterosexual contact) and with subtype (subtype C presented significantly more TDR when compared to subtype B). TC analysis corroborated that the heterosexual risk group presented a higher proportion of TDR in TCs when compared to MSMs. Among subtype A1, TDR reached 16.6% in heterosexuals, followed by 14.2% in patients infected with subtype B and 9.4% in patients infected with subtype G. Conclusion: Our molecular epidemiology approach indicates that the HIV-1 epidemic in Portugal is changing among risk group populations, with heterosexuals showing increasing levels of HIV-1 transmission and TDR. Prevention measures for this subpopulation should be reinforced.info:eu-repo/semantics/publishedVersio
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