Don't forget the jumper's knee in the young sportsman: evaluation of patellar tendinopathy with a high frequency ultrasound probe.

8Patellar tendinopathy, or Jumper's knee, is a painful knee condition caused by inflammation of the patella tendon. This condition is most frequently observed in subjects who play sports that require repetitive regular jumping. Jumper's knee is frequently misdiagnosed as a minor injury and many athletes, like our patient, keep on training and competing and either tend to ignore the injury or attempt to treat it themselves. However, jumper's knee is a serious condition that requires a correct and timely diagnosis, which often necessitates ultrasound investigation in order to start the most appropriate treatment.openopenRuaro B; Cutolo M; Alessandri E; Zaottini F; Picasso R; Pistoia F; Ferrari G; Martinoli C.Ruaro, B; Cutolo, M; Alessandri, E; Zaottini, F; Picasso, R; Pistoia, F; Ferrari, G; Martinoli, C

Alternatively Activated (M2) Macrophage Phenotype Is Inducible by Endothelin-1 in Cultured Human Macrophages.

Background Alternatively activated (M2) macrophages are phenotypically characterized by the expression of specific markers, mainly macrophage scavenger receptors (CD204 and CD163) and mannose receptor-1 (CD206), and participate in the fibrotic process by over-producing profibrotic molecules, such as transforming growth factor-beta1 (TGFbeta1) and metalloproteinase (MMP)-9. Endothelin-1 (ET-1) is implicated in the fibrotic process, exerting its profibrotic effects through the interaction with its receptors (ETA and ETB). The study investigated the possible role of ET-1 in inducing the transition from cultured human macrophages into M2 cells. Methods Cultured human monocytes (THP-1 cell line) were activated into macrophages (M0 macrophages) with phorbol myristate acetate and subsequently maintained in growth medium (M0-controls) or treated with either ET-1 (100nM) or interleukin-4 (IL-4, 10ng/mL, M2 inducer) for 72 hours. Similarly, primary cultures of human peripheral blood monocyte (PBM)-derived macrophages obtained from healthy subjects, were maintained in growth medium (untreated cells) or treated with ET-1 or IL-4 for 6 days. Both M0 and PBM-derived macrophages were pre-treated with ET receptor antagonist (ETA/BRA, bosentan 10-5M) for 1 hour before ET-1 stimulation. Protein and gene expression of CD204, CD206, CD163, TGFbeta1 were analysed by immunocytochemistry, Western blotting and quantitative real time polymerase chain reaction (qRT-PCR). Gene expression of interleukin(IL)-10 and macrophage derived chemokine (CCL-22) was evaluated by qRT-PCR. MMP-9 production was investigated by gel zymography. Results ET-1 significantly increased the expression of M2 phenotype markers CD204, CD206, CD163, IL-10 and CCL-22, and the production of MMP-9 in both cultures of M0 and PBMderived macrophages compared to M0-controls and untreated cells. In cultured PBMderived macrophages, ET-1 increased TGFbeta1 protein and gene expression compared to untreated cells. The ET-1-mediated effects were contrasted by ETA/BRA treatment in both cultured cell types. Conclusion ET-1 seems to induce the M2 phenotype in cultured human macrophages, a process apparently contrasted by the action of the ETA/BRA, suggesting possible clinical implications in those fibrotic diseases characterized by increased ET-1 concentrations, such as systemic sclerosis but also type 2 diabetes

A circulating cell population showing both M1 and M2 monocyte/macrophage surface markers characterizes systemic sclerosis patients with lung involvement.

Background: Systemic sclerosis (SSc) is a disorder characterized by immune system alterations, vasculopathy and fibrosis. SSc-related interstitial lung disease (ILD) represents a common and early complication, being the leading cause of mortality. Monocytes/macrophages seem to have a key role in SSc-related ILD. Interestingly, the classically (M1) and alternatively (M2) activated monocyte/macrophage phenotype categorization is currently under revision. Our aim was to evaluate if circulating monocyte/macrophage phenotype could be used as biomarker for lung involvement in SSc. To this purpose we developed a wide phenotype characterization of circulating monocyte/macrophage subsets in SSc patients and we evaluated possible relations with lung involvement parameter values. Methods: A single centre cross-sectional study was performed in fifty-five consecutive SSc patients, during the year 2017. All clinical and instrumental tests requested for SSc follow up and in particular, lung computed tomography (CT) scan, pulmonary function tests (PFTs), Doppler echocardiography with systolic pulmonary artery pressure (sPAP) measurement, blood pro-hormone of brain natriuretic peptide (pro-BNP) evaluation, were performed in each patient in a maximum one-month period. Flow cytometry characterization of circulating cells belonging to the monocyte/macrophage lineage was performed using specific M1 (CD80, CD86, TLR2 and TLR4) and M2 surface markers (CD204, CD163 and CD206). Non-parametric tests were used for statistical analysis. Results: A higher percentage of circulating CD204 + CD163 + CD206 + TLR4 + CD80 + CD86 + and CD14 + CD206 + CD163 + CD204 + TLR4 + CD80 + CD86 + mixed M1/M2 monocyte/macrophage subsets, was identified to characterize patients affected by SSc-related ILD and higher systolic pulmonary artery pressure. Mixed M1/M2 monocyte/macrophage subset showed higher percentages in patients positive for anti-topoisomerase antibody, a known lung involvement predictor. Conclusions: The present study shows for the first time, through a wide flow cytometry surface marker analysis, that higher circulating mixed M1/M2 monocyte/macrophage cell percentages are associated with ILD, sPAP and anti-topoisomerase antibody positivity in SSc, opening the path for research on their possible role as pathogenic or biomarker elements for SSc lung involvement

Host-Based Treatments for Severe COVID-19

COVID-19 has been a global health problem since 2020. There are different spectrums of manifestation of this disease, ranging from asymptomatic to extremely severe forms requiring admission to intensive care units and life-support therapies, mainly due to severe pneumonia. The progressive understanding of this disease has allowed researchers and clinicians to implement different therapeutic alternatives, depending on both the severity of clinical involvement and the causative molecular mechanism that has been progressively explored. In this review, we analysed the main therapeutic options available to date based on modulating the host inflammatory response to SARS-CoV-2 infection in patients with severe and critical illness. Although current guidelines are moving toward a personalised treatment approach titrated on the timing of presentation, disease severity, and laboratory parameters, future research is needed to identify additional biomarkers that can anticipate the disease course and guide targeted interventions on an individual basis

Expedient microwave-assisted synthesis of Bis( n )-lophine analogues as selective butyrylcholinesterase inhibitors: Cytotoxicity evaluation and molecular modelling

In the brain of patients with chronic Alzheimer's disease (AD), the butyrylcholinesterase (BuChE) levels rise while the acetylcholinesterase (AChE) levels decrease. Therefore, development of new selective BuChE inhibitors is of vital importance. Here we present a series of bis(n)-lophine analogues, where two lophine derivatives are connected by a methylene chain. The bis(n)-lophine analogues were synthesized through one-pot four component reaction between pyridinecarboxaldehydes, 1,n-alkanediamines, benzil, and ammonium acetate. The reactions were performed in a microwave reactor in one step for symmetrical bis(n)-lophines, and in two steps for unsymmetrical bis(n)-lophines. The compounds are strongly selective to BuChE, since none of them inhibit AChE. All the compounds, except 7a, 7b and 7c, displayed potent inhibitory activity against BuChE at a micromolar and sub-micromolar range (half maximal inhibitory concentration (IC50) 32.25-0.03 μM). The enzyme kinetic and docking studies suggests that the inhibitor act as a dual binding site inhibitor, binding into the bottom of the gorge and in the peripheral anionic site (PAS) of BuChE cavity. Furthermore, in vitro studies showed that compounds 5b and 12b had no cytotoxic effects in kidney Vero, hepatic HepG2 and C6 astroglial cell lines.Fil: Câmara, Viktor S.. Universidade Federal do Rio Grande do Sul; BrasilFil: Soares, Ana Julia. Universidade Federal do Rio Grande do Sul; BrasilFil: Biscussi, Brunella. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; ArgentinaFil: Murray, Ana Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; ArgentinaFil: Guedes, Isabella A.. Laboratório Nacional de Computação Científica; BrasilFil: Dardenne, Laurent E.. Laboratório Nacional de Computação Científica; BrasilFil: Ruaro, Thaís C.. Universidade Federal do Rio Grande do Sul; BrasilFil: Zimmer, Aline R.. Universidade Federal do Rio Grande do Sul; BrasilFil: Ceschi, Marco A.. Universidade Federal do Rio Grande do Sul; Brasi

Avaliação da produção de grãos e massa seca de cinco genótipos de trigo duplo propósito.

Resumo: O trigo duplo propósito é uma alternativa para atender a necessidade de forragem no vazio forrageiro outonal e ainda proporcionar a colheita de grãos. Objetivou-se avaliar a produtividade de matéria seca e grãos de cinco genótipos de trigo duplo propósito na região das Missões-RS. Utilizou-se parcelas de 5m2 e espaçamento entre linhas de 0,0017m, sendo semeadas as cultivares BRS Pastoreio e BRS Tarumã e as linhagens PF150088, PF170297 e PF170306, indicadas e disponibilizadas pela Embrapa Trigo. O delineamento experimental foi blocos ao acaso com três tratamentos (sem corte, um corte e dois cortes) e três repetições. Avaliou-se a produção de matéria seca e grãos. A BRS Pastoreio em ausência de corte foi a maior produtora de grãos. Nos demais tratamentos os genótipos não diferiram, em relação a produção de grãos, nem matéria seca. Logo, as linhagens adaptam-se ao manejo de duplo propósito, sendo importante dar continuidade aos ensaios de avaliação

Searching for plasticity in dissociated cortical cultures on multi-electrode arrays

We attempted to induce functional plasticity in dense cultures of cortical cells using stimulation through extracellular electrodes embedded in the culture dish substrate (multi-electrode arrays, or MEAs). We looked for plasticity expressed in changes in spontaneous burst patterns, and in array-wide response patterns to electrical stimuli, following several induction protocols related to those used in the literature, as well as some novel ones. Experiments were performed with spontaneous culture-wide bursting suppressed by either distributed electrical stimulation or by elevated extracellular magnesium concentrations as well as with spontaneous bursting untreated. Changes concomitant with induction were no larger in magnitude than changes that occurred spontaneously, except in one novel protocol in which spontaneous bursts were quieted using distributed electrical stimulation

Avaliação de linhagens e cultivares de trigo duplo propósito.

Resumo: O trigo duplo propósito é uma alternativa de diversificação produtiva, fornecendo forragem aos bovinos durante o vazio forrageiro outonal e gerando receita com a colheita de grãos. Objetivou-se realizar a avaliação da produção de matéria seca e grãos de cinco genótipos de trigo duplo propósito. Sendo, as cultivares BRS Pastoreio e BRS Tarumã e as linhagens, PF180161, PF180168 e PF180169. As parcelas experimentais foram de 5 m² com espaçamento entre linhas de 0,017m, dispostos em blocos ao acaso, com três repetições e três tratamentos (sem corte, um corte e dois cortes). Avaliou-se a produção de matéria seca e grãos. Os genótipos não diferiram em relação a produção de matéria seca. À produção de grãos da BRS Pastoreio, PF180161 e PF180169 foram superiores, sendo seguida da PF180168 e BRS Tarumã, respectivamente, no tratamento sem corte; nos demais tratamentos não diferiram. Portanto, ambos os genótipos atendem a proposta de dupla aptidão satisfatoriamente

Decreased Gas6 and sAxl Plasma Levels Are Associated with Hair Loss in COVID-19 Survivors

: Post-acute conditions after coronavirus disease 2019 (COVID-19) are quite common, although the underlying pathogenetic mechanisms leading to these conditions are not yet completely understood. In this prospective observational study, we aimed to test the hypothesis that Growth Arrest-Specific 6 (Gas6) and its soluble receptors, Axl (sAxl) and MerTK (sMer), might be implicated. A total of 263 subjects underwent a structured clinical evaluation one year after their hospital discharge for COVID-19, and they consented to donate a blood sample to measure their circulating Gas6, sAxl, and sMer levels. A total of 98 (37.3%) post-COVID-19 subjects complained of at least one residual physical symptom one year after their hospital discharge. Univariate analysis revealed that sAxl was marginally associated with residual symptoms, but at the level of logistic regression analysis, only the diffusing capacity of the lungs for carbon monoxide (DLCO) (OR 0.98, CI 95%: 0.96-0.99; p = 0.007) and the female sex (OR 2.49, CI 95%: 1.45-4.28; p = 0.001) were independently associated with long-lasting symptoms. A total of 69 (26.2%) subjects had hair loss. At the level of univariate analysis, Gas6, sAxl, DLCO, and the female gender were associated with its development. In a logistic regression analysis model, Gas6 (OR 0.96, CI 95%: 0.92-0.99; p = 0.015) and sAxl (OR 0.98, CI 95%; 0.97-1.0; p = 0.014), along with the female sex (OR 6.58, CI 95%: 3.39-12.78; p = 0.0001), were independent predictors of hair loss. Decreased levels of Gas6 and sAxl were associated with a history of hair loss following COVID-19. This was resolved spontaneously in most patients, although 23.7% complained of persistent hair loss one year after hospital discharge