Influence of structural and process parameters on mechanical behaviour of elastane yarns

In this work, the influence of various structural and process parameters (such as linear density of core and cover and draw ratio) on the mechanical behaviour of elastane yarn has been thoroughly investigated. According to the experimental results, elastane yarns with high linear density core and cover and produced using higher draw ratio showed the best mechanical properties in terms of both strength and extension

The acute impact of the early stages of COVID-19 pandemic in people with pre-existing psychiatric disorders: a systematic review

People with pre-pandemic health conditions are more vulnerable and more likely to suffer greater psychosocial impact due to the current COVID-19 pandemic and the lockdown measures. Thus, the objective of this work was to systematically review the impact of the early stages COVID-19 pandemic on people with pre-existing psychiatric disorders. The search was performed between 23 January and 2 September 2021 in PubMed, PsycINFO, and EMBASE. A total of 4167 published results were identified; however, only 49 were included in this review. Results show that there was considerable heterogeneity among studies, which resulted in a low consensus. However, it seems that the impact of the first stage of the COVID-19 pandemic on psychiatric disorders was two-fold: (1) an overall effect, in which people suffering from psychiatric disorders in general experienced more psychological distress and anxiety when compared to people who had no psychiatric diagnosis, and (2) a condition-specific effect, namely in people suffering from eating disorders and obsessive compulsive disorders. Moreover, the current work highlights that there were also some external factors that were related to worsening symptoms. For instance, unemployment or experiencing work and financial difficulties can be a trigger for greater distress during the pandemic for people with mood disorders, and being alone and in social isolation during the COVID-19 pandemic may actually increase substance use and relapse rates. Further studies are needed to prospectively investigate the long-term effects of the current COVID-19 pandemic on people with (pre)-existing psychiatric conditions and on the onset or deterioration of psychiatric-related symptoms in a larger number of participants, as well as exploring the long-term effects of the current pandemic on mental health.This work was partially supported by FEDER funds through the Programa Operacional Factores de Competitividade-COMPETE, by national funds through FCT-Fundação para a Ciência e a Tecnologia through the projects PTDC/PSI-ESP/29701/2017 and PTDC/PSI-ESP/30280/2017. It was also supported by grant FCT UIDB/04810/2020 from the Portuguese Foundation for Science and Technology to the William James Center for Research

Induction of pyroptotic cell death as a potential tool for cancer treatment

Cancer is a complex pathological disease and the existing strategies for introducing chemotherapeutic agents have restricted potential due to a lack of cancer cell targeting specificity, cytotoxicity, bioavailability, and induction of multi-drug resistance. As a prospective strategy in tackling cancer, regulating the inflammatory pyroptosis cell death pathway has been shown to successfully inhibit the proliferation and metastasis of various cancer cell types. Activation of inflammasomes such as the NLRP3 results in pyroptosis through cleavage of gasdermins, which forms pores in the cell membranes, inducing membrane breakage, cell rupture, and death. Furthermore, pyroptotic cells release pro-inflammatory cytokines such as IL-1β and IL-18 along with various DAMPs that prime an auxiliary anti-tumor immune response. Thus, regulation of pyroptosis in cancer cells is a way to enhance their immunogenicity. However, immune escape involving myeloid-derived suppressor cells has limited the efficacy of most pyroptosis-based immunotherapy strategies. In this review, we comprehensively summarize the cellular and molecular mechanisms involved in the inflammasome-mediated pyroptosis pathways in cancer cells, exploring how it could modulate the tumor microenvironment and be beneficial in anti-cancer treatments. We discuss various existing therapeutic strategies against cancer, including immunotherapy, oncolytic virus therapy, and nanoparticle-based therapies that could be guided to trigger and regulate pyroptosis cell death in cancer cells, and reduce tumor growth and spread. These pyroptosis-based cancer therapies may open up fresh avenues for targeted cancer therapy approaches in the future and their translation into the clinic

Secreted extracellular vesicle molecular cargo as a novel liquid biopsy diagnostics of central nervous system diseases

Secreted extracellular vesicles (EVs) are heterogeneous cell-derived membranous granules which carry a large diversity of molecules and participate in intercellular communication by transferring these molecules to target cells by endocytosis. In the last decade, EVs role in several pathological conditions, from etiology to disease progression or therapy evasion, has been consolidated, including in central nervous system (CNS)-related disorders. For this review, we performed a systematic search of original works published, reporting the presence of molecular components expressed in the CNS via EVs, which have been purified from plasma, serum or cerebrospinal fluid. Our aim is to provide a list of molecular EV components that have been identified from both nonpathological conditions and the most common CNS-related disorders. We discuss the methods used to isolate and enrich EVs from specific CNS-cells and the relevance of its components in each disease context.This research was funded by the MindGaP-H2020-FETOPEN-2018-2020, Grant agreement ID: 829040. S.M.-R., C.C.-M., and J.P. hold a fellowship from MindGaP.info:eu-repo/semantics/publishedVersio

Eine Phantasie der Allmacht. Vom Versprechen des an die Technologie angepassten Lernens

Die Autoren analysieren nach der Methode der Objektiven Hermeneutik den das brasilianische Werbevideo der Lernplattform "Moodle". Es wird sowohl der Slogan als auch die Bildpräsentation und damit die Funktionsweise der Lernplattform sequenzanalytisch rekonstruiert. Dabei zeigt sich, wie die Lernplattform nicht nur die Funktion der Lehrenden entprofessionalisiert, sondern auch das Vermittelte zur Nebensache gerät. Die Art und Weise, wie die Plattform den Schüler und die Schülerin an sie bindet, wird als reine Anpassung gekennzeichnet. (DIPF/Orig.

Linkage disequilibrium in Brazilian Santa Inês breed, \u3ci\u3eOvis aries\u3c/i\u3e

For genomic selection to be successful, there must be sufficient linkage disequilibrium between the markers and the causal mutations. The objectives of this study were to evaluate the extent of LD in ovine using the Santa Inês breed and to infer the minimum number of markers required to reach reasonable prediction accuracy. In total, 38,168 SNPs and 395 samples were used. The mean LD between adjacent marker pairs measured by r2 and |D′| were 0.166 and 0.617, respectively. LD values between adjacent marker pairs ranged from 0.135 to 0.194 and from 0.568 to 0.650 for r2 for |D′| across all chromosomes. The average r2 between all pairwise SNPs on each chromosome was 0.018. SNPs separated by between 0.10 to 0.20 Mb had an estimated average r2 equal to 0.1033. The identified haplotype blocks consisted of 2 to 21 markers. Moreover, estimates of average coefficients of inbreeding and effective population size were 0.04 and 96, respectively. LD estimated in this study was lower than that reported in other species and was characterized by short haplotype blocks. Our results suggest that the use of a higher density SNP panel is recommended for the implementation of genomic selection in the Santa Inês breed

Trichosporon asahii an emerging etiologic agent of fungal infection and colonization in heart failure patients in intensive care unit: case report and literature review

JUSTIFICATIVA E OBJETIVOS: As infecções fúngicas por Trichosporon Asahii têm sido cada vez mais freqüentes nas últimas duas décadas. Quadros graves com alta mortalidade são tradicionalmente descritos em pacientes neutropênicos com câncer. Recentemente, a infecção tem ocorrido também em outros grupos de pacientes. O objetivo deste estudo foi descrever a crescente prevalência de Trichosporon asahii em unidade de terapia intensiva cardiológica (UTIC), com perfil de pacientes habitualmente não susceptíveis a tal infecção fúngica, relatar um caso clínico e revisão da literatura. RELATO DO CASO: Paciente do sexo feminino, 85 anos, com antecedentes de hipertensão arterial sistêmica, insuficiência cardíaca (fração de ejeção = 30%) e embolia pulmonar, admitida na UTI depois de parada cardiorrespiratória em fibrilação ventricular durante consulta de rotina. Evoluiu sem seqüela neurológica. O ecocardiograma não revelou alterações em relação ao exame anterior. Não houve alteração dos indicadores de necrose miocárdica. A paciente apresentou falha na extubação traqueal e desmame difícil, necessitando ventilação mecânica prolongada mesmo após traqueostomia. Houve complicações por insuficiência renal aguda e infecções recorrentes (respiratória, urinária e sistêmica), com boa resposta ao tratamento com antibióticos de amplo espectro. Após sete meses de internação na UTI, evoluiu com choque séptico, associado à infecção urinária por Trichosporon asahii, com hemoculturas identificadas pelo mesmo fungo. Iniciado tratamento com anfotericina B lipossomal (5 mg/kg/dia). Apesar do uso associado de vancomicina e imipenem, houve piora clínica progressiva. Hemoculturas colhidas no sétimo dia de uso de antifúngico revelaram-se negativas, porém a urocultura ainda revelou o crescimento de T. asahii. Evoluiu com óbito após 18 dias de tratamento, por falência de múltiplos órgãos. CONCLUSÕES: O aumento da gravidade dos pacientes internados nas UTI e o uso disseminado de antibióticos de amplo espectro têm possibilitado o surgimento de infecções por fungos incomuns. As infecções graves por Trichosporon asahii, descritas como restritas a pacientes imunossuprimidos, oncológicos e hematológicos, têm sido freqüentemente encontradas em pacientes idosos, com insuficiência cardíaca grave e com alta mortalidade intra-hospitalar, internados em UTI. Deve-se estar atento à possibilidade da emergência de infecções por fungos não usuais em pacientes com este perfil clínico.BACKGROUND AND OBJECTIVES: Infection with the non-Candida yeast species Trichosporon have been recognized with increasing frequency over the last two decades. Invasive disease due to trichosporonosis has been reported from neutropenic patients with cancer and the mortality is high. Recently, others groups of patients have become susceptible to this rare fungi. We report the emerging of infection with pathogenic Trichosporon asahii in severely ill heart failure patients in a tertiary cardiological intensive care unit (CICU). We describe our data, and report a fatal case of disseminated trichosporonosis in a patient with heart failure. We also review literature pertaining to T. asahii infections. CASE REPORT: An 85 year-old woman with a history of hypertension, heart failure (ejection fraction (EJ): 30%) and pulmonary embolism was admitted to a medical cardiological ICU after cardiac arrest (ventricular fibrillation) resuscitated during a routine consultation. There were no neurological sequelae and the echocardiogram revels no changes, neither the cardiac biomarkers. Ventricular fibrillation was considered secondary to heart failure. The patient had extubation failure and difficult weaning needing long term mechanical ventilation even after tracheostomy. Her hospital course was complicated by acute renal failure and recurrent respiratory, urinary and systemic bacterial infections, which responded to broad-spectrum antibiotics. After a temporary improvement she developed urinary infection and subsequent septic shock. Cultures of urine and blood specimens grew T. asahii. Treatment with liposome amphotericin B (5 mg/kg/day) was started. Despite receiving vancomycin and imipenem, the clinical condition of the patient deteriorates. Blood taken for culture on the seventh day of amphotericin B therapy were negative but urine specimen still grew T. asahii. On the eighteenth day of antifungal therapy, the patient died with multiorgan failure. CONCLUSIONS: The increasing of severely ill patients, and the use of broad spectrum antibiotics, has predisposed the emerging of invasive infections by rare and new opportunistic fungal pathogens. Severe infection related to T. asahii, until recently restricted to neutropenic patients with cancer, has been frequently identified in heart failure patients with advanced age. The mortality is high. These data highlights the importance of considering this group of patients as a risk group for T. asahii infection

Targeting p53 for melanoma treatment: counteracting tumour proliferation, dissemination and therapeutic resistance

Melanoma is the deadliest form of skin cancer, primarily due to its high metastatic propensity and therapeutic resistance in advanced stages. The frequent inactivation of the p53 tumour suppressor protein in melanomagenesis may predict promising outcomes for p53 activators in melanoma therapy. Herein, we aimed to investigate the antitumor potential of the p53-activating agent SLMP53-2 against melanoma. Two- and three-dimensional cell cultures and xenograft mouse models were used to unveil the antitumor activity and the underlying molecular mechanism of SLMP53-2 in melanoma. SLMP53-2 inhibited the growth of human melanoma cells in a p53-dependent manner through induction of cell cycle arrest and apoptosis. Notably, SLMP53-2 induced p53 stabilization by disrupting the p53–MDM2 interaction, enhancing p53 transcriptional activity. It also promoted the expression of p53-regulated microRNAs (miRNAs), including miR-145 and miR-23a. Moreover, it displayed anti-invasive and antimigratory properties in melanoma cells by inhibiting the epithelial-to-mesenchymal transition (EMT), angiogenesis and extracellular lactate production. Importantly, SLMP53-2 did not induce resistance in melanoma cells. Additionally, it synergized with vemurafenib, dacarbazine and cisplatin, and resensitized vemurafenib-resistant cells. SLMP53-2 also exhibited antitumor activity in human melanoma xenograft mouse models by repressing cell proliferation and EMT while stimulating apoptosis. This work discloses the p53-activating agent SLMP53-2 which has promising therapeutic potential in advanced melanoma, either as a single agent or in combination therapy. By targeting p53, SLMP53-2 may counteract major features of melanoma aggressiveness.This work received financial support from PT national funds (FCT/MCTES, Fundação para a Ciência e Tecnologia and Ministério da Ciência, Tecnologia e Ensino Superior) through LAQV/REQUIMTE (UID/QUI/50006/2020), iMed.ULisboa (UIDB/04138/2020), and PTDC/QUIQOR/29664/2017, PTDC/MEC-ONC/32018/2017. We thank FCT for the fellowships SFRH/BD/ 128673/2017 (J. Loureiro), 2020.04613.BD (J. Calheiros), PD/BD/143126/2019 (V. Barcherini)

Mitochondrial retrograde signaling through UCP1-mediated inhibition of the plant oxygen-sensing pathway

Mitochondrial retrograde signaling is an important component of intracellular stress signaling in eukaryotes. UNCOUPLING PROTEIN (UCP)1 is an abundant plant inner-mitochondrial membrane protein with multiple functions including uncoupled respiration and amino-acid transport1,2 that influences broad abiotic stress responses. Although the mechanism(s) through which this retrograde function acts is unknown, overexpression of UCP1 activates expression of hypoxia (low oxygen)-associated nuclear genes.3,4 Here we show in Arabidopsis thaliana that UCP1 influences nuclear gene expression and physiological response by inhibiting the cytoplasmic PLANT CYSTEINE OXIDASE (PCO) branch of the PROTEOLYSIS (PRT)6 N-degron pathway, a major mechanism of oxygen and nitric oxide (NO) sensing.5 Overexpression of UCP1 (UCP1ox) resulted in the stabilization of an artificial PCO N-degron pathway substrate, and stability of this reporter protein was influenced by pharmacological interventions that control UCP1 activity. Hypoxia and salt-tolerant phenotypes observed in UCP1ox lines resembled those observed for the PRT6 N-recognin E3 ligase mutant prt6-1. Genetic analysis showed that UCP1 regulation of hypoxia responses required the activity of PCO N-degron pathway ETHYLENE RESPONSE FACTOR (ERF)VII substrates. Transcript expression analysis indicated that UCP1 regulation of hypoxia-related gene expression is a normal component of seedling development. Our results show that mitochondrial retrograde signaling represses the PCO N-degron pathway, enhancing substrate function, thus facilitating downstream stress responses. This work reveals a novel mechanism through which mitochondrial retrograde signaling influences nuclear response to hypoxia by inhibition of an ancient cytoplasmic pathway of eukaryotic oxygen sensing