DESMANTELAR LA CASA DEL AMO: LAS FORMAS DE LA RESISTENCIA FEMINISTA SEGÚN AUDRE LORDE

as múltiples opresiones que sufrieron las mujeres afroestadounidenses quienes se sintieron excluidas de lasluchas llevadas adelante por el feminismo blanco heterosexual, motivó la introducción en la discusiónfeminista de la idea de que el género interactúa con otras categorías tales como la clase, la raza y laorientación sexual. La segunda ola del feminismo, inspirada en el radicalismo marxista de los años sesenta,el movimiento hippie y las luchas por los derechos civiles, implicó un mayor protagonismo por parte de losmovimientos y grupos feministas de mujeres negras. La perspectiva propuesta desde el feminismo negrobuscaba reemplazar los modelos aditivos de opresión por un único modelo de análisis antirracista, antisexistay anticolonialista que comprendiera la raza, la clase y el género como sistemas que si bien sonestructuralmente diferentes, están entrelazados en la práctica. En este contexto toma relevancia la figura deAudre Lorde, una de las activistas negras más reconocidas por sus luchas contra las injusticias del racismo,el sexismo y la homofobia. Su producción poética y ensayística puede ser entendida como una operaciónpolítica y como un llamado a la reconfiguración de los espacios de visibilidad delimitados por el poder WASP.Al tiempo que nos permite reflexionar acerca de la noción de diferencia como fuerza creativa y de la escriturafemenina como forma de resistencia, sus postulados permiten revisar el complejo entramado de una matrizde dominación mucha más compleja. DISMANTLING THE MASTER’S HOUSE: AUDRE LORDE’S FORMS OFFEMINIST RESISTANCEAbstractThe multiple oppressions suffered by African American women, who felt excluded from the discussions heldby white heterosexual feminists, encouraged the introduction of the idea that gender interacts with othercategories such as class, race and sexual orientation. The second wave of feminism, inspired by the radicalMarxism of the sixties, the hippie movement and the fights for the civil rights, implied a prominence of themovements and groups of black women. The perspective proposed from black feminism looked forwardreplacing the model of oppression for a unique model of antiracist, antisexist and anticolonialist analysis thatunderstands race, class and gender as systems, that even though they are structurally different, can beconsidered as interlaced. In this context gains importance the figure of Audre Lorde, one of the mostremarkable black activists, better known for her fights against racism, sexism and homophobia. Her poemsand essays can be understood as a political operation and a call for the reconfiguration of the visibility spots,those who are defined by the WASP power. While she allows the reflection about difference as a creativeforce, her hypotheses are useful in the process of revising a much more complex domination system.Key words: feminism; second wave; african american women; political operation; poetr

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P < .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

Autisms

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition with onset in early childhood, characterized by deficits in social interaction and communication, stereotypic behaviors, insistence on sameness, restricted interests and abnormal sensory processing. Its prevalence has risen during the last three decades from 2-5/10,000 to 1:59 children. ASD encompasses a collection of neurodevelopmental conditions sharing similar behavioral features but extremely heterogenous etiopathogenetic underpinnings. This chapter initially reviews the history of the concept of “autism”, the clinical diagnosis, epidemiology, co-morbidities, developmental trajectories and early signs. The pathophysiology of ASD is then described, spanning neuropsychology, neuroanatomy, functional brain imaging and electrophysiology, as well as systemic gastrointestinal and immune dysfunction. The complex etiology of ASD spans from genetic syndroms and non-syndromic autisms due to rare and common variants, to environmental forms and epigenetic contributions. Current evidence-based clinical pharmacological and behavioral intervention paradigms are finally outlined, as well as therapeutic perspectives opened by experimental psychopharmacology and iPSC models

Chiral analysis of amino acids from conventional and transgenic yeasts

Autolysis of Saccharomyces cerevisiae yeast is the main source of molecules that contribute to the quality of sparkling wines made by the traditional method. In this work, a genetically modified yeast (LS11) is compared to its isogenic wild type strain (BY4741) after autolysis. Chiral micellar electrokinetic chromatography with laser-induced fluorescence detection (chiral-MEKC–LIF) is used to identify and quantify the main d- and l-amino acids from both strains after accelerated autolysis. The procedure includes amino acids extraction, derivatization with FITC and chiral-MEKC–LIF separation in a background electrolyte composed of 100 mM sodium tetraborate, 30 mM SDS, 20 mM β-CD at pH 10.0. The d- and l-forms of Arg, Asn, Ala, Glu and Asp, corresponding to the major amino acids found in these samples, are separated in less than 30 min with efficiencies up to 800,000 plates/m and high sensitivity (i.e., LODs as low as 40 nM were obtained for d-Arg for a signal to noise ratio of three). From these results it is corroborated that the genetic modification brings a faster autolysis of the yeast, releasing a higher amount of l-amino acids to the medium in a short time. Interestingly, the pattern of release of d-amino acids was also different between the transgenic and the conventional yeast strains.This work was supported by Projects AGL2005-05320-C02-01 and Consolider Ingenio 2010 CSD2007-00063 FUN-C-FOOD (Ministerio de Educación y Ciencia), S-505/AGR-0153 (ALIBIRD, Comunidad de Madrid) and HA2006-0057 (Ministerio de Educación y Ciencia).Peer reviewe

LRRK2 Inhibition by PF06447475 Antagonist Modulates Early Neuronal Damage after Spinal Cord Trauma

Spinal cord injury (SCI) is a devastating event followed by neurodegeneration, activation of the inflammatory cascade, and immune system. The leucine-rich-repeat kinase 2 (LRRK2) is a gene associated with Parkinson’s disease (PD), moreover, its kinase activity was found to be upregulated after instigated inflammation of the central nervous system (CNS). Here, we aimed to investigate the PF06447475 (abbreviated as PF-475) role as a pharmacological LRRK2 antagonist by counteracting pathological consequences of spinal cord trauma. The in vivo model of SCI was induced by extradural compression of the spinal cord, then mice were treated with PF0-475 (2.5–5 and 10 mg/kg i.p) 1 and 6 h after SCI. We found that PF-475 treatments at the higher doses (5 and 10 mg/kg) showed a great ability to significantly reduce the degree of spinal cord tissue injury, glycogen accumulation, and demyelination of neurons associated with trauma. Furthermore, oxidative stress and cytokines expression levels, including interleukins (IL-1, IL-6, IL-10, and 12), interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α), secreted and released after trauma were decreased by LRRK2 antagonist treatments. Our results suggest that the correlations between LRRK2 and inflammation of the CNS exist and that LRRK2 activity targeting could have direct effects on the intervention of neuroinflammatory disorders

Effect of Melatonin on Psoriatic Phenotype in Human Reconstructed Skin Model

Psoriasis is an inflammatory and auto-immune skin-disease characterized by uncontrolled keratinocyte proliferation. Its pathogenesis is not still fully understood; however, an aberrant and excessive inflammatory and immune response can contribute to its progression. Recently, more attention has been given to the anti-inflammatory and immunomodulators effects of melatonin in inflammatory diseases. The aim of this paper was to investigate the effect of melatonin on psoriatic phenotype and also in S. aureus infection-associated psoriasis, with an in vitro model using Skinethic Reconstructed Human Epidermis (RHE). An in vitro model was constructed using the RHE, a three-dimensional-model obtained from human primary-keratinocytes. RHE-cells were exposed to a mix of pro-inflammatory cytokines, to induce a psoriatic phenotype; cells were also infected with S. aureus to aggravate psoriasis disease, and then were treated with melatonin at the concentrations of 1 nM, 10 nM, and 50 nM. Our results demonstrated that melatonin at higher concentrations significantly reduced histological damage, compared to the cytokine and S. aureus groups. Additionally, the treatment with melatonin restored tight-junction expression and reduced pro-inflammatory cytokine levels, such as interleukin-1β and interleukin-12. Our results suggest that melatonin could be considered a promising strategy for psoriasis-like skin inflammation, as well as complications of psoriasis, such as S. aureus infection

Prolyl oligopeptidase inhibition ameliorates experimental pulmonary fibrosis both in vivo and in vitro

Abstract Background Pulmonary fibrosis is a progressive disease characterized by lung remodeling due to excessive deposition of extracellular matrix. Although the etiology remains unknown, aberrant angiogenesis and inflammation play an important role in the development of this pathology. In this context, recent scientific research has identified new molecules involved in angiogenesis and inflammation, such as the prolyl oligopeptidase (PREP), a proteolytic enzyme belonging to the serine protease family, linked to the pathology of many lung diseases such as pulmonary fibrosis. Therefore, the aim of this study was to investigate the effect of a selective inhibitor of PREP, known as KYP-2047, in an in vitro and in an in vivo model of pulmonary fibrosis. Methods The in vitro model was performed using human alveolar A549 cells. Cells were exposed to lipopolysaccharide (LPS) 10 μg/ml and then, cells were treated with KYP-2047 at the concentrations of 1 μM, 10 μM and 50 μM. Cell viability was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) bromide colorimetric assay, while inflammatory protein expression was assessed by western blots analysis. The in vivo model was induced in mice by intra-tracheal administration of bleomycin (1 mg/kg) and then treated intraperitoneally with KYP-2047 at doses of 1, 2.5 and 5 mg/kg once daily for 12 days and then mice were sacrificed, and lung tissues were collected for analyses. Results The in vitro results demonstrated that KYP-2047 preserved cell viability, reduced inflammatory process by decreasing IL-18 and TNF-α, and modulated lipid peroxidation as well as nitrosative stress. The in vivo pulmonary fibrosis has demonstrated that KYP-2047 was able to restore histological alterations reducing lung injury. Our data demonstrated that KYP-2047 significantly reduced angiogenesis process and the fibrotic damage modulating the expression of fibrotic markers. Furthermore, KYP-2047 treatment modulated the IκBα/NF-κB pathway and reduced the expression of related pro-inflammatory enzymes and cytokines. Moreover, KYP-2047 was able to modulate the JAK2/STAT3 pathway, highly involved in pulmonary fibrosis. Conclusion In conclusion, this study demonstrated the involvement of PREP in the pathogenesis of pulmonary fibrosis and that its inhibition by KYP-2047 has a protective role in lung injury induced by BLM, suggesting PREP as a potential target therapy for pulmonary fibrosis. These results speculate the potential protective mechanism of KYP-2047 through the modulation of JAK2/STAT3 and NF-κB pathways. Graphical abstrac

Urinary Untargeted Metabolic Profile Differentiates Children with Autism from Their Unaffected Siblings

Autism Spectrum Disorder (ASD) encompasses a clinical spectrum of neurodevelopmental conditions that display significant heterogeneity in etiology, symptomatology, and severity. We previously compared 30 young children with idiopathic ASD and 30 unrelated typically-developing controls, detecting an imbalance in several compounds belonging mainly to the metabolism of purines, tryptophan and other amino acids, as well as compounds derived from the intestinal flora, and reduced levels of vitamins B6, B12 and folic acid. The present study describes significant urinary metabolomic differences within 14 pairs, including one child with idiopathic ASD and his/her typically-developing sibling, tightly matched by sex and age to minimize confounding factors, allowing a more reliable identification of the metabolic fingerprint related to ASD. By using a highly sensitive, accurate and unbiased approach, suitable for ensuring broad metabolite detection coverage on human urine, and by applying multivariate statistical analysis, we largely replicate our previous results, demonstrating a significant perturbation of the purine and tryptophan pathways, and further highlight abnormalities in the “phenylalanine, tyrosine and tryptophan” pathway, essentially involving increased phenylalanine and decreased tyrosine levels, as well as enhanced concentrations of bacterial degradation products, including phenylpyruvic acid, phenylacetic acid and 4-ethylphenyl-sulfate. The outcome of these within-family contrasts consolidates and extends our previous results obtained from unrelated individuals, adding further evidence that these metabolic imbalances may be linked to ASD rather than to environmental differences between cases and controls. It further underscores the excess of some gut microbiota-derived compounds in ASD, which could have diagnostic value in a network model differentiating the metabolome of autistic and unaffected siblings. Finally, it points toward the existence of a “metabolic autism spectrum” distributed as an endophenotype, with unaffected siblings possibly displaying a metabolic profile intermediate between their autistic siblings and unrelated typically-developing controls