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Perceived job quality is a key indicator of sustainable work among persons with spinal cord injuries (PwSCI). This study aimed at (a) describing three indicators of perceived job quality (i.e. job satisfaction, job performance, and work stress) among working PwSCI, and (b) identifying whether and how different person-job match dimensions (i.e. interest congruence, demands-abilities fit, needs-supplies fit, and effort-reward imbalance) as well as sociodemographic and health-related factors (e.g. age, sex, SCI-related characteristics, pain problems, and depressive symptoms) are associated with perceived job quality. Cross-sectional, self-report survey. Community. 549 working-age PwSCI who participated in the 2017 community survey of the Swiss Spinal Cord Injury Cohort study and reported being engaged in paid work. Job satisfaction, job performance, and work stress. Higher interest congruence, better needs-supplies fit and lower effort-reward imbalance, as well as female sex, were associated with higher job satisfaction, while higher effort-reward imbalance, poorer demands-abilities fit (underqualification), and – surprisingly – better needs-supplies fit were associated with higher work stress. Moreover, underqualification, worse needs-supplies fit as well as pain, depressive symptoms, and language region were associated with lower job performance. Integrating individuals in jobs that match their abilities, interests and needs, and which adequately reward their efforts may contribute to better job quality among PwSCI. Beyond that, common secondary health conditions and comorbidities such as pain and depressive symptoms should receive particular attention in interventions that aim to promote job quality and ultimately sustainable work in the SCI population.

Background: Previous interim data from a phase I study of AKS-452, a subunit vaccine comprising an Fc fusion of the respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein receptor binding domain (SP/RBD) emulsified in the water-in-oil adjuvant, Montanide™ ISA 720, suggested a good safety and immunogenicity profile in healthy adults. This phase I study was completed and two dosing regimens were further evaluated in this phase II study.Methods: This phase II randomized, open-labelled, parallel group study was conducted at a single site in The Netherlands with 52 healthy adults (18 – 72 years) receiving AKS-452 subcutaneously at one 90 µg dose (cohort 1, 26 subjects) or two 45 µg doses 28 days apart (cohort 2, 26 subjects). Serum samples were collected at the first dose (day 0) and at days 28, 56, 90, and 180. Safety and immunogenicity endpoints were assessed, along with induction of IgG isotypes, cross-reactive immunity against viral variants, and IFN-γ T cell responses.Results: All AEs were mild/moderate (grades 1 or 2), and no SAEs were attributable to AKS-452. Seroconversion rates reached 100% in both cohorts, although cohort 2 showed greater geometric mean IgG titers that were stable through day 180 and associated with enhanced potencies of SP/RBD-ACE2 binding inhibition and live virus neutralization. AKS-452-induced IgG titers strongly bound mutant SP/RBD from several SARS-CoV-2 variants (including Omicrons) that were predominantly of the favorable IgG1/3 isotype and IFN-γ-producing T cell phenotype.Conclusion: These favorable safety and immunogenicity profiles of the candidate vaccine as demonstrated in this phase II study are consistent with those of the phase I study (ClinicalTrials.gov: NCT04681092) and suggest that a total of 90 µg received in 2 doses may offer a greater duration of cross-reactive neutralizing titers than when given in a single dose.

Este artigo tem como objetivo analisar os desafios e possibilidades encontradas no estudo da deriva educacional, condição em que os sujeitos já estiveram na escola, mas foram dela excluídos antes de concluir a educação básica, sendo responsabilizados pelo retorno aos estudos. Trata-se de um ensaio teórico-metodológico que foca no pensamento categorial, sobretudo a categoria da dimensão subjetiva como recurso para apreensão da concreticidade do fenômeno social estudado. A deriva educacional é um fenômeno social pouco estudado no campo da Psicologia da Educação e a possibilidade de explicá-lo é desafiadora, tendo em vista as armadilhas presentes nos discursos carregados da intenção de ocultar o modo como se trata de uma condição social e historicamente determinada no modo de produção capitalista. Diante dessa dificuldade, ter como base teórico-metodológica o Materialismo Histórico-dialético (MHD) e a Psicologia Sócio-histórica (PSH) foi fundamental. O pensamento categorial possibilitou, partindo das significações dos participantes da pesquisa, superar as múltiplas camadas de aparência para compreender a deriva educacional em sua complexidade. A categoria da dimensão subjetiva e o processo de análise por meio dos núcleos de significação possibilitaram chegar a uma síntese das múltiplas determinações da deriva educacional que permitiu explicá-la de forma contra-hegemônica, apontando para os movimentos já existentes ou ainda necessários para a transformação, sem recorrer à justificativas individualizantes, psicologizantes ou sociologizantes.

Context: Cross-education (CE) refers to neuromuscular gains in the untrained limb upon contralateral limb training. To date, only laboratory-based exercise programs have demonstrated CE. Home-based exercise prescription eliciting CE could have greater clinical applicability. Objective: To determine the effect of an 8-week, home-based unilateral strength training intervention on isokinetic muscle strength, muscular excitation, and power in trained and untrained plantar flexors. Design: Randomized controlled trial. Methods: Thirty-four healthy participants were randomized to intervention (n = 20) or control (n = 14). The intervention group completed 3 sets of 12 repetitions of progressively loaded unilateral calf raises 3 days per week. Concentric and eccentric peak torque were measured using isokinetic dynamometry at 30°/s and 120°/s. Maximal electromyogram amplitude was simultaneously measured. Power was measured using a jump mat. All variables were measured at preintervention, midintervention, and postintervention. Results: Strength significantly increased bilaterally pre–post at both velocities concentrically and eccentrically in intervention group participants. Maximal electromyogram amplitude significantly increased pre–post bilaterally at both velocities in the medial gastrocnemii of the intervention group. Power significantly increased bilaterally pre–post in the intervention group, with a dose–response effect demonstrated in the untrained plantar flexors. The CE effects of strength, power, and electromyogram activation were 23.4%, 14.6%, and 25.3%, respectively. All control group values were unchanged pre–post. Conclusion: This study shows that a simple at-home unilateral plantar flexor exercise protocol induces significant increases in contralateral strength, muscular excitation, and power. These results suggest the applicability of CE in home rehabilitation programs aiming to restore or maintain neuromuscular function in inactive individuals or immobilized ankles.

Art experience is not solely the observation of artistic objects, but great relevance is also placed on the environment in which the art experience takes place, often in museums and galleries. Interestingly, in the last few years, the introduction of some forms of virtual reality (VR) in museum contexts has been increasing. This has solicited enormous research interest in investigating any eventual differences between looking at the same artifact either in a real context (e.g. a museum) and in VR. To address such a target, a neuroaesthetic study was performed in which electroencephalography (EEG) and autonomic signals (heart rate and skin conductance) were recorded during the observation of the Etruscan artifact “Sarcophagus of the Spouses”, both in the museum and in a VR reproduction. Results from EEG analysis showed a higher level of the Workload Index during observation in the museum compared to VR (p = 0.04), while the Approach–Withdrawal Index highlighted increased levels during the observation in VR compared to the observation in the museum (p = 0.03). Concerning autonomic indices, the museum elicited a higher Emotional Index response than the VR (p = 0.03). Overall, preliminary results suggest a higher engagement potential of the museum compared to VR, although VR could also favour higher embodiment than the museum.

Este texto origina-se de uma pesquisa acadêmica a qual investiga as diferentes percepções de qualidade em duas creches públicas municipais, localizadas na região leste da capital paulista. A pesquisa teve participação de mães, professoras e coordenadoras pedagógicas, cujos depoimentos foram coletados por meio de entrevistas semiestruturadas e de caráter reflexivo. O material das entrevistas foi analisado qualitativamente, à luz da Análise de Conteúdo (AC), com base nestas categorias: Creche, lugar de formação para a vida; A creche é uma instituição complexa; A criança como centro da proposta pedagógica. Para fins deste artigo, focalizaremos a relação creche-família, entendida pelas participantes do estudo como um dos aspectos que configuram a complexidade dessa instituição educativa. Os resultados corroboram a discussão da área sobre os desafios presentes na efetivação da integração entre escola e família, a importância da dialogicidade e de se pensar estratégias e ações que viabilizem a participação dos diferentes sujeitos escolares, valorizando sua dimensão de protagonistas da transformação da realidade em que vivem. Por fim, as múltiplas vozes analisadas colocam em evidência o papel social e político da creche na promoção de direitos fundamentais e exercício da cidadania desde a infância, e acentuam a compreensão de que a qualidade não é dada a priori, mas depende de múltiplos fatores.

Este artigo analisa as concepções, as potencialidades e os desafios específicos da docência na educação infantil,sob o enfoque da qualidade social da educação. Para tanto, busca entrelaçar as vozes de professoras ecoordenadoras pedagógicas que atuam na rede municipal de ensino paulistana com as vozes presentes emdocumentos oficiais em vigor. Como procedimento de coleta de dados, empregou-se análise documental eentrevistas semiestruturadas. A análise dos dados busca inspiração na Análise de Conteúdo. Os resultadosassinalam, entre outros aspectos, a importância de legitimar indicadores de qualidade (social) construídos com aparticipação das educadoras que atuam na primeiríssima infância.

In January 2020, we instituted acute febrile illness surveillance in 11 hospitals and clinics across Belize. Within 3 months, we diagnosed an acute case of Chagas disease by polymerase chain reaction in a 7-year-old child in the northern part of the country. Phylogenetic analyses of the parasite from the acute blood specimen revealed a multiclonal Trypanosoma cruzi infection, including parasites from the TcII (25.0% of haplotypes), TcIV (2.5% of haplotypes), and TcV (72.5% of haplotypes) discrete typing units. The family reported no history of travel, and three Triatoma species vectors were found within the home. The child’s mother was seronegative for antibodies to T. cruzi, ruling out congenital transmission. Convalescent blood samples documented seroconversion and confirmed acute infection. The child was successfully treated with nifurtimox. This is the first known diagnosed case of acute Chagas infection in Belize, highlighting the need for further investigation and public health prevention measures.

Despite that metallic glasses are among the most studied metallic materials, still very little is known on the evolution of their unique structural, dynamical and elastic properties under compression, owing to the difficulty to perform in-situ high pressure experiments. Coupling the brightest x-rays available in synchrotrons with cutting edge high pressure technologies, we provide direct evidence of the microscopic structural and dynamical mechanisms occurring under in-situ high pressure compression and decompression in the GPa range, from the onset of the perturbation up to a severely-deformed state. We show that while pressure promotes density increasing through quasi-elastic structural deformations, the atomic mobility exhibits a hysteresis and is enhanced up to a factor 15 even at temperatures well below the glass transition. This surprising behaviour results from a competition between fast avalanche-like atomic rearrangements and slow relaxation processes triggered by an anomalous super-diffusive collective particle displacement. These results provide new insights on the effect of deformation in non-ergodic materials and support the occurrence of string-like diffusion of liquid-like atoms in metallic glasses. They explain also the macroscopic impressive rejuvenation and strain hardening reported recently under ex-situ densifications. This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (Grant Agreement No 948780). Peer Reviewed Objectius de Desenvolupament Sostenible::9 - Indústria, Innovació i Infraestructura::9.5 - Augmentar la investigació científica i millorar la capacitat tecnològica dels sectors industrials de tots els països, en particular els països en desenvolupament, entre d’altres maneres fomentant la innovació i augmentant substancialment, d’aquí al 2030, el nombre de persones que treballen en el camp de la investigació i el desenvolupa­ment per cada milió d’habitants, així com la despesa en investigació i desenvolupament dels sectors públic i privat Objectius de Desenvolupament Sostenible::9 - Indústria, Innovació i Infraestructura

Pathological angiogenesis is a crucial attribute of several chronic diseases such as cancer, age-related macular degeneration, and osteoarthritis (OA). In the case of OA, pathological angiogenesis mediated by the vascular endothelial growth factor (VEGF), among other factors, contributes to cartilage degeneration and to implants rejection. In line with this, the use of the anti-VEGF bevacizumab (BVZ) has been shown to prevent OA pro- gression and support cartilage regeneration. The aim of this work was to functionalize a medical grade collagen with poly (lactic-co-glycolic acid) (PLGA) microparticles containing BVZ via three-dimensional (3D) printing to target pathological angiogenesis. First, the effect of several formulation parameters on the encapsulation and release of BVZ from PLGA microparticles was studied. Then, the anti-angiogenic activity of released BVZ was tested in a 3D cell model. The 3D printability of the microparticle-loaded collagen ink was tested by evaluating the shape fidelity of 3D printed structures. Results showed that the release and the encapsulation efficiency of BVZ could be tuned as a function of several formulation parameters. In addition, the released BVZ was observed to reduce vascularization by human umbilical vein endothelial cells. Finally, the collagen ink with embedded BVZ microparticles was successfully printed, leading to shape-stable meniscus-, nose- and auricle-like structures. Taken altogether, we defined the conditions for the successful combination of BVZ-loaded microparticles with the 3D printing of a medical grade collagen to target pathological angiogenesis.

Loss of function variants of LIPG gene encoding endothelial lipase (EL) are associated with primary hyperalphalipoproteinemia (HALP), a lipid disorder characterized by elevated plasma levels of high density lipoprotein cholesterol (HDL-C).Aim of the study was the phenotypic and genotypic characterization of a family with primary HALP.HDL subclasses distribution was determined by polyacrylamide gradient gel electrophoresis. Serum content of preβ-HDL was assessed by (2D)-electrophoresis. Cholesterol efflux capacity (CEC) of serum mediated by ABCA1, ABCG1 or SR-BI was assessed using cells expressing these proteins. Cholesterol loading capacity (CLC) of serum was assayed using cultured human macrophages. Next generation sequencing was used for DNA analysis. Plasma EL mass was determined by ELISA.Three family members had elevated plasma HDL-C, apoA-I and total phospholipids, as well as a reduced content of preβ-HDL. These subjects were heterozygous carriers of a novel variant of LIPG gene [c.526 GT, p.(Gly176Trp)] found to be deleterious in silico. Plasma EL mass in carriers was lower than in controls. CEC of sera mediated by ABCA1 and ABCG1 transporters was substantially reduced in the carriers. This effect was maintained after correction for serum HDL concentration. The sera of carriers were found to have a higher CLC in cultured human macrophages than control sera.The novel p.(Gly176Trp) variant of endothelial lipase is associated with changes in HDL composition and subclass distribution as well as with functional changes affecting cholesterol efflux capacity of serum which suggest a defect in the early steps of revere cholesterol transport.

The capability of measuring specific neurophysiological and autonomic parameters plays a crucial role in the objective evaluation of a human’s mental and emotional states. These human aspects are commonly known in the scientific literature to be involved in a wide range of processes, such as stress and arousal. These aspects represent a relevant factor especially in real and operational environments. Neurophysiological autonomic parameters, such as Electrodermal Activity (EDA) and Photoplethysmographic data (PPG), have been usually investigated through research-graded devices, therefore resulting in a high degree of invasiveness, which could negatively interfere with the monitored user’s activity. For such a reason, in the last decade, recent consumer-grade wearable devices, usually designed for fitness-tracking purposes, are receiving increasing attention from the scientific community, and are characterized by a higher comfort, ease of use and, therefore, by a higher compatibility with daily-life environments. The present preliminary study was aimed at assessing the reliability of a consumer wearable device, i.e., the Fitbit Sense, with respect to a research-graded wearable, i.e., the Empatica E4 wristband, and a laboratory device, i.e., the Shimmer GSR3+. EDA and PPG data were collected among 12 participants while they performed multiple resting conditions. The results demonstrated that the EDA- and PPG-derived features computed through the wearable and research devices were positively and significantly correlated, while the reliability of the consumer device was significantly lower.

Ocimum basilicum (sweet basil) is an economically important aromatic herb; in Italy, approximately 1000 ha of “Genovese-type” basil are grown annually in greenhouses and open fields and are subjected to Downy Mildew (DM) disease, caused by Peronospora belbahrii, leading to huge crop losses. Mutation of the Susceptibility (S) gene DMR6 (Downy Mildew Resistant 6) has been proven to confer a broad-spectrum resistance to DM. In this work, an effective Genome Editing (GE) approach mediated by CRISPR/Cas9 in O. basilicum ‘Italiko’, the élite cultivar used to produce “Pesto Genovese D.O.P”, was developed. A highly efficient genetic transformation method mediated by A. tumefaciens has been optimized from cotyledonary nodes, obtaining 82.2% of regenerated shoots, 84.6% of which resulted in Cas9+ plants. Eleven T0 lines presented different type of mutations in ObDMR6; 60% were indel frameshift mutations with knock-out of ObDMR6 of ‘FT Italiko’. Analysis of six T1 transgene-free seedlings revealed that the mutations of T0 plants were inherited and segregated. Based on infection trials conducted on T0 plants, clone 22B showed a very low percentage of disease incidence after 14 days post infection. The aromatic profile of all in vitro edited plants was also reported; all of them showed oxygenated monoterpenes as the major fraction.

Strong coupling between molecules and quantized fields has emerged as an effective methodology to engineer molecular properties. New hybrid states are formed when molecules interact with quantized fields. Since the properties of these states can be modulated by fine-tuning the field features, an exciting and new side of chemistry can be explored. In particular, significant modifications of the molecular properties can be achieved in plasmonic nanocavities, where the field quantization volume is reduced to sub-nanometric volumes. Intriguing applications of nanoplasmonics include the possibility of coupling the plasmons with a single molecule, instrumental for sensing, high-resolution spectroscopy, and single-molecule imaging. In this work, we focus on phenomena where the simultaneous effects of multiple plasmonic modes are critical. We propose a theoretical methodology to account for many plasmonic modes simultaneously while retaining computational feasibility. Our approach is conceptually simple and allows us to accurately account for the multimode effects and rationalize the nature of the interaction between multiple plasmonic excitations and molecules., 27 pages, 6 figures

Several studies have shown a potential protective role of long pentraxin 3 (PTX3) in different lung pathologies. In the present study, we have explored the influence of PTX3 in the bleomycin (BLM)-induced murine model of Idiopathic Pulmonary Fibrosis (IPF). We made a picture of the pulmonary microenvironment by looking at inflammatory infiltrate (macrophages, mast cells, T cells) and stemness/regenerative markers of lung epithelium (SOX2) and fibroblasts/myofibroblasts (CD44) at different time points that retrace the progression of the disease from onset at day 14, to full-blown disease at day 21, to incomplete regression at day 28. We took advantage of transgenic PTX3 overexpressing mice (Tie2-PTX3) and Ptx3 null ones (PTX3-KO) in which IPF was indued. Our data have shown that: throughout the whole experimental period, the CD68+ and CD163+ macrophages and the Tryptase+ mast cells are reduced in the Tie2-PTX3 pulmonary microenvironment compared to wild-type (WT) or PTX3-KO; on the contrary, CD4+ T cells are consistently present on day 14 and dramatically decreased on day 21 in Tie2-PTX3 compared to WT or PTX3-KO; CD8+ T cells do not show significant differences on day 14, but are significantly reduced on day 21 in Tie2-PTX3 compared to WT or PTX3-KO; SOX2 is reduced on days 14 and 21 in Tie2-PTX3 compared to WT or PTX3-KO; CD44 is reduced on day 21 in Tie2-PTX3 compared to WT or PTX3-KO. This scenario demonstrates the anti-inflammatory effects of PTX3, which reduces pro-inflammatory cells and counteracts profibrotic events.

The N-terminal region of troponin T (TnT) does not bind any protein of the contractile machinery and the role of its hypervariability remains uncertain. In this review we report the evidence of the interaction between TnT and AMP deaminase (AMPD), a regulated zinc enzyme localized on the myofibril. In periods of intense muscular activity, a decrease in the ATP/ADP ratio, together with a decrease in the tissue pH, is the stimulus for the activation of the enzyme that deaminating AMP to IMP and NH3 displaces the myokinase reaction towards the formation of ATP. In skeletal muscle subjected to strong tetanic contractions, a calpain-like proteolytic activity produces the removal in vivo of a 97-residue N-terminal fragment from the enzyme that becomes desensitized towards the inhibition by ATP, leading to an unrestrained production of NH3. When a 95-residue N-terminal fragment is removed from AMPD by trypsin, simulating in vitro the calpain action, rabbit fast TnT or its phosphorylated 50-residue N-terminal peptide binds AMPD restoring the inhibition by ATP. Taking in consideration that the N-terminus of TnT expressed in human as well as rabbit white muscle contains a zinc-binding motif, we suggest that TnT might mimic the regulatory action of the inhibitory N-terminal domain of AMPD due to the presence of a zinc ion connecting the N-terminal and C-terminal regions of the enzyme, indicating that the two proteins might physiologically associate to modulate muscle contraction and ammonia production in fast-twitching muscle under strenuous conditions.

Infection with West Nile Virus (WNV) can drive a wide range of responses, from asymptomatic to flu-like symptoms/fever or severe cases of encephalitis and death. To identify cellular and molecular signatures distinguishing WNV severity, we employed systems profiling of peripheral blood from asymptomatic and severely ill individuals infected with WNV. We interrogated immune responses longitudinally from acute infection through convalescence at 3 months and 1 year employing multiplexed single cell protein and transcriptional profiling (CyTOF and Seq-Well) complemented with matched serum proteomics and metabolomics. At the acute time point, we detected both an elevated proportion of pro-inflammatory markers in innate immune cell types and reduced frequency of regulatory T cell activity in participants with severe infection compared to those with asymptomatic infection. Single-cell transcriptomics of paired samples revealed that asymptomatic donors had higher expression of genes associated with innate immune pathways, in particular anti-inflammatory CD16+monocytes at the acute time point. A multi-omics analysis identified factors--beyond those from individual analyses--that distinguished immune state trajectory between severity groups. Here we highlighted the potential of systems immunology using multiple cell-type and cell-state-specific analyses to identify correlates of infection severity and host cellular activity contributing to an effective anti-viral response.

Background Cancer stem-like cells (CSCs) are a subpopulation of tumor cells responsible for tumor initiation, metastasis, chemoresistance, and relapse. Recently, CSCs have been identified in Uveal Melanoma (UM), which represents the most common primary tumor of the eye. UM is highly resistant to systemic chemotherapy and effective therapies aimed at improving overall survival of patients are eagerly required. Methods Herein, taking advantage from a pan Fibroblast Growth Factor (FGF)-trap molecule, we singled out and analyzed a UM-CSC subset with marked stem-like properties. A hierarchical clustering of gene expression data publicly available on The Cancer Genome Atlas (TCGA) was performed to identify patients’ clusters. Results By disrupting the FGF/FGF receptor (FGFR)-mediated signaling, we unmasked an FGF-sensitive UM population characterized by increased expression of numerous stemness-related transcription factors, enhanced aldehyde dehydrogenase (ALDH) activity, and tumor-sphere formation capacity. Moreover, FGF inhibition deeply affected UM-CSC survival in vivo in a chorioallantoic membrane (CAM) tumor graft assay, resulting in the reduction of tumor growth. At clinical level, hierarchical clustering of TCGA gene expression data revealed a strong correlation between FGFs/FGFRs and stemness-related genes, allowing the identification of three distinct clusters characterized by different clinical outcomes. Conclusions Our findings support the evidence that the FGF/FGFR axis represents a master regulator of cancer stemness in primary UM tumors and point to anti-FGF treatments as a novel therapeutic strategy to hit the CSC component in UM.

Polaritonic chemistry is an interdisciplinary emerging field that presents several challenges and opportunities in chemistry, physics, and engineering. A systematic review of polaritonic response theory is presented, following a chemical perspective based on molecular response theory. We provide the reader with a general strategy for developing response theory for ab initio cavity quantum electrodynamics (QED) methods and critically emphasize details that still need clarification and require cooperation between the physical and chemistry communities. We show that several well-established results can be applied to strong coupling light-matter systems, leading to novel perspectives on the computation of matter and photonic properties. The application of the Pauli-Fierz Hamiltonian to polaritons is discussed, focusing on the effects of describing operators in different mathematical representations. We thoroughly examine the most common approximations employed in ab initio QED, such as the dipole approximation. We introduce the polaritonic response equations for recently developed ab initio QED Hartree-Fock and QED coupled cluster methods. The discussion focuses on the similarities and differences from standard quantum chemistry methods, providing practical equations for computing the polaritonic properties., 37 pages, 3 figures

Objective: The objective of this study was to evaluate the influence of the presence of siblings with normal development on the burden and quality of life of parents of adolescents with Down syndrome. Methods: Cross sectional and correlational study with 25 caregivers divided in two groups: parents who had only children with Down syndrome and parents with other children with normal development. The caregivers were selected from a convenient sample and answered the World Health Organization Quality of Life, Zarit Burden Interview and Brazil’s Economic Classification Criteria. Results: It was found that both groups experienced moderate burden and regular quality of life for most families, with no significant difference. Conclusion: It was concluded that the presence of siblings with normal development was not a factor influencing the burden and quality of life of parents of adolescents with Down syndrome. Resumo Objetivo: O objetivo deste estudo foi avaliar a influência da presença de irmãos com desenvolvimento típico na sobrecarga e na qualidade de vida de pais de adolescentes com síndrome de Down. Métodos: Foi realizado um estudo transversal e correlacional, com 25 cuidadores divididos em dois grupos: pais com filhos únicos com síndrome de Down e pais com outros filhos com desenvolvimento típico. Os cuidadores foram selecionados a partir de uma amostragem de conveniência e responderam ao World Health Organization Quality of Life, ao Zarit Burden Interview e ao Critério de Classificação Econômica Brasil. Resultados: Verificou-se que ambos os grupos apresentaram sobrecarga moderada e qualidade de vida regular para a maioria das famílias, não havendo diferença significativa. Conclusão: Conclui-se que a presença de irmãos com desenvolvimento típico não foi fator de influência na sobrecarga e na qualidade de vida de pais de adolescentes com síndrome de Down.

During melanoma progression, malignant melanocytes are reprogrammed into mesenchymal-like cells through to an epithelial–mesenchymal transition (EMT) process associated with the acquisition of an invasive, prometastatic phenotype. The fibroblast growth factor-2 (FGF2)/FGF receptor (FGFR) system plays a pivotal role in melanoma, leading to autocrine/paracrine induction of tumor cell proliferation and angiogenesis. Long pentraxin-3 (PTX3) interacts with FGF2, and other FGF family members, inhibiting FGF-dependent neovascularization and tumor growth. Here, PTX3 protein and the PTX3-derived acetylated pentapeptide Ac-ARPCA-NH2 inhibit FGF2-driven proliferation and downstream FGFR signaling in murine melanoma B16-F10 cells. Moreover, human PTX3-overexpressing hPTX_B16-F10 cells are characterized by the reversed transition from a mesenchymal to an epithelial-like appearance, inhibition of cell proliferation, loss of clonogenic potential, reduced motility and invasive capacity, downregulation of various mesenchymal markers, and upregulation of the epithelial marker E-cadherin. Accordingly, PTX3 affects cell proliferation and EMT transition in human A375 and A2058 melanoma cells. Also, hPTX_B16-F10 cells showed a reduced tumorigenic and metastatic activity in syngeneic C57BL/6 mice. In conclusion, PTX3 inhibits FGF/FGFR-driven EMT in melanoma cells, hampering their tumorigenic and metastatic potential. These data represent the first experimental evidence about a nonredundant role of the FGF/FGFR system in the modulation of the EMT process in melanoma and indicate that PTX3 or its derivatives may represent the basis for the design of novel therapeutic approaches in FGF/FGFR-dependent tumors, including melanoma. Mol Cancer Ther; 12(12); 2760–71. ©2013 AACR.

PDF - 44KB, Legends to Supplementary Figures S1-S4.

PDF - 37KB, hPTX3 overexpression in B16-F10 cells.

PDF - 117KB, PTX3 expression in human melanoma.

PDF - 114KB, Morphogenic assay on Matrigel.

PDF - 65KB, Matrigel implant assay.

PDF file - 142K

PDF - 33KB, List of oligonucleotide primers utilized for PCR experiments.

Fibroblast growth factor-8b (FGF8b) exerts nonredundant autocrine/paracrine functions in steroid hormone–regulated tumors. Previous observations had shown that the soluble pattern recognition receptor long pentraxin-3 (PTX3) is a natural selective antagonist for a restricted number of FGF family members, inhibiting FGF2 but not FGF1 and FGF4 activity. Here, we assessed the capacity of PTX3 to antagonize FGF8b and to inhibit the vascularization and growth of steroid hormone–regulated tumors. Surface plasmon resonance analysis shows that PTX3 binds FGF8b with high affinity (Kd = 30–90 nmol/L). As a consequence, PTX3 prevents the binding of FGF8b to its receptors, inhibits FGF8b-driven ERK1/2 activation, cell proliferation, and chemotaxis in endothelial cells, and suppresses FGF8b-induced neovascularization in vivo. Also, PTX3 inhibits dihydrotestosterone (DHT)- and FGF8b-driven proliferation of androgen-regulated Shionogi 115 (S115) mouse breast tumor cells. Furthermore, DHT-treated, PTX3 overexpressing hPTX3_S115 cell transfectants show a reduced proliferation rate in vitro and a limited angiogenic activity in the chick embryo chorioallantoic membrane and murine s.c. Matrigel plug assays. Accordingly, hPTX3_S115 cells show a dramatic decrease of their tumorigenic activity when grafted in immunodeficient male mice. These results identify PTX3 as a novel FGF8b antagonist endowed with antiangiogenic and antineoplastic activity with possible implications for the therapy of hormonal tumors. Mol Cancer Ther; 10(9); 1600–10. ©2011 AACR.

We present the analytic evaluation of the two-loop corrections to the amplitude for the scattering of four fermions in Quantum Electrodynamics, $f^- + f^+ + F^- + F^+ \to 0$, with $f$ and $F$ representing a massless and a massive lepton, respectively. Dimensional regularization is employed to evaluate the loop integrals. Ultraviolet divergences are removed by renormalizing the coupling constant in the ${\overline{\text{MS}}}$-scheme, and the lepton mass as well as the external fields in the on-shell scheme. The analytic result for the renormalized amplitude is expressed as Laurent series around $d=4$ space-time dimensions, and contains Generalized Polylogarithms with up to weight four. The structure of the residual infrared divergences of the virtual amplitude is in agreement with the prediction of the Soft Collinear Effective Theory. Our analytic results are an essential ingredient for the computation of the scattering cross section for massive fermion-pair production in massless fermion-pair annihilation, i.e. $f^- f^+ \to F^- F^+$, and crossing related processes such as the elastic scattering $f F \to f F$, with up to Next-to-Next to Leading Order accuracy., Comment: 5 pages, 2 figures, 1 table + supplemental material. v2: references added; plots added; Table 1: finite part of A(2) fixed; matches published version

Waiting list mortality together, with limited availability of organs, are one of the major challenges in liver transplantation (LT). Especially in the paediatric population, another limiting factor is the scarcity of transplantable liver grafts due to additional concerns regarding graft size matching. In adults, donation after circulatory death (DCD) liver grafts have been used to expand the donor pool with satisfactory results. Although several studies suggest that DCD livers could also be used in paediatric recipients with good outcomes, their utilisation in children is still limited to a small number of reports. Novel organ perfusion strategies could be used to improve organ quality and help to increase the number of DCD grafts utilised for children. With the current manuscript, we present the available literature of LT using DCD grafts in paediatric recipients, discussing current challenges with the use of these livers in children and how machine perfusion technologies could be of impact in the future.

In patients with cirrhosis with severe thrombocytopenia (platelet count [PC] 100 × 109/L), intermediate (51‐100 × 109/L), and low (≤50 × 109/L). PC was also analyzed as a continuous covariate on multivariable analysis. The primary endpoint was major perioperative bleeding. The overall event rate of major perioperative bleeding was 8.9% and was not found to differ significantly between the high, intermediate, and low platelet groups (8.1% vs. 10.2% vs. 10.8%, P = 0.48). On multivariable analysis, greater age, aspartate aminotransferase, lower hemoglobin, and treatment with LR (vs. RFA) were found to be significant independent predictors of major perioperative bleeding, with associations with disease etiology and year of surgery also observed. After adjusting for these factors, the association between PC and major perioperative bleeding remained nonsignificant. Conclusion: Major perioperative bleeding was not significantly associated with PC in patients with cirrhosis undergoing surgical treatment of HCC, even when their PC was

Carbonic anhydrase IX/XII (CA IX/XII), are cell-surface enzymes typically expressed by cancer cells as a form of adaptation to hypoxia and acidosis. It has been widely reported that these proteins play pivotal roles in cancer progression fostering cell migration, aggressiveness and resistance to first line chemo- and radiotherapies. CA IX has emerged as a promising target in cancer therapy and several approaches and families of compounds were characterised in the attempt to find optimal targeting by inhibiting of the high catalytic activity of the enzyme. In the present work, different cell lines representing glioblastoma, bladder and pancreatic cancer have been exploited to compare the inhibitory and antiproliferative effect of primary sulphonamide acetazolamide (AAZ), the Phase Ib/II clinical grade sulphonamide SLC-0111, and a membrane-impermeant positively charged, pyridinium-derivative (C18). New hints regarding the possibility to exploit CA inhibitors in these cancer types are proposed.

This study aimed to analyze the content of the District Food and Nutrition Policy’s public consultation, present the participants’ profiles, and report the systematization of the analysis performed. This is a documentary, exploratory, cross-sectional study with a qualitative and quantitative approach. The initial sample consisted of 115 inputs, with 59 exclusions and 56 retained for the content analysis described by Bardin and multivariate analysis by frequency (p

As human space exploration advances to establish a permanent presence beyond the Low Earth Orbit (LEO) with NASA’s Artemis mission, researchers are striving to understand and address the health challenges of living and working in the spaceflight environment. Exposure to ionizing radiation, microgravity, isolation and other spaceflight hazards pose significant risks to astronauts. Determining neurobiological and neurobehavioral responses, understanding physiological responses under Central Nervous System (CNS) control, and identifying putative mechanisms to inform countermeasure development are critically important to ensuring brain and behavioral health of crew on long duration missions. Here we provide a detailed and comprehensive review of the effects of spaceflight and of ground-based spaceflight analogs, including simulated weightlessness, social isolation, and ionizing radiation on humans and animals. Further, we discuss dietary and non-dietary countermeasures including artificial gravity and antioxidants, among others. Significant future work is needed to ensure that neural, sensorimotor, cognitive and other physiological functions are maintained during extended deep space missions to avoid potentially catastrophic health and safety outcomes.

The Figure shows the long term behavior of sensitive and resistant cells (in absence of enzalutamide

Enzalutamide does not induce apoptosis in TRAMP-C2 cells

HT10806TG_CBL0137 treatment

Disturbance of sphingolipid metabolism may represent a novel therapeutic target in metastatic melanoma, the most lethal form of skin cancer. β-Galactosylceramidase (GALC) removes β-galactose from galactosylceramide and other sphingolipids. In this study, we show that downregulation of galcb, a zebrafish ortholog of human GALC, affects melanoblast and melanocyte differentiation in zebrafish embryos, suggesting a possible role for GALC in melanoma. On this basis, the impact of GALC expression in murine B16-F10 and human A2058 melanoma cells was investigated following its silencing or upregulation. Galc knockdown hampered growth, motility, and invasive capacity of B16-F10 cells and their tumorigenic and metastatic activity when grafted in syngeneic mice or zebrafish embryos. Galc-silenced cells displayed altered sphingolipid metabolism and increased intracellular levels of ceramide, paralleled by a nonredundant upregulation of Smpd3, which encodes for the ceramide-generating enzyme neutral sphingomyelinase 2. Accordingly, GALC downregulation caused SMPD3 upregulation, increased ceramide levels, and inhibited the tumorigenic activity of human melanoma A2058 cells, whereas GALC upregulation exerted opposite effects. In concordance with information from melanoma database mining, RNAscope analysis demonstrated a progressive increase of GALC expression from common nevi to stage IV human melanoma samples that was paralleled by increases in microphthalmia transcription factor and tyrosinase immunoreactivity inversely related to SMPD3 and ceramide levels. Overall, these findings indicate that GALC may play an oncogenic role in melanoma by modulating the levels of intracellular ceramide, thus providing novel opportunities for melanoma therapy.Significance:Data from zebrafish embryos, murine and human cell melanoma lines, and patient-derived tumor specimens indicate that β-galactosylceramidase plays an oncogenic role in melanoma and may serve as a therapeutic target.

Supplementary Data from Antiangiogenic Activity of a Neutralizing Human Single-Chain Antibody Fragment against Fibroblast Growth Factor Receptor 1

Fibroblast growth factor receptor-1 (FGFR-1) transduces proangiogenic and proliferative signals in human cancers. Thus, FGFR-1 may represent a target for the development of antiangiogenic/antineoplastic therapies. We screened a human single-chain fragment variable (scFv) antibody phage display library against the extracellular domain of the FGFR-1-IIIc isoform that harbors the FGF binding site. Several phages were isolated and tested for specificity and sensitivity, and the most promising antibody fragment RR-C2 was characterized for its biochemical and biological properties. ScFv RR-C2 specifically recognizes FGFR-1α and FGFR-1β isoforms in ELISA, Western blotting, and surface plasmon resonance analysis with a Kd value of 300 and 144 nmol/L for the 2 receptor isoforms, respectively. The antibody fragment also recognizes FGFR-1 when the receptor is exposed on the cell surface, thus preventing the formation of the ternary complex among FGFR-1, its ligand FGF2, and cell surface heparan sulfate proteoglycans. Accordingly, scFv RR-C2 specifically inhibits FGF2-mediated mitogenic activity in endothelial cells of human, bovine, and murine origin in a nanomolar range of concentrations. Also, the antibody fragment prevents FGF2-triggered sprouting of both human umbilical vein endothelial cell spheroids and of murine endothelium from aortic rings. Finally, the antibody fragment hampers the angiogenic activity exerted both by FGF2 in the chick embryo chorioallantoic membrane assay and by S115 mouse mammary tumor cells in the Matrigel plug assay. Taken together, the data show that scFv RR-C2 recognizes and neutralizes FGFR-1 activity in different animal species, including humans, thus representing a novel tool for the development of antiangiogenic/antineoplastic therapies. Mol Cancer Ther; 9(12); 3244–53. ©2010 AACR.

Supplementary Data - Single file with supplemental methods, tables, figures, legends. Supplemental Materials and Methods; Table S1: Primers used for RT-qPCR analysis; Table S2: GALC downregulation affects the lipid profile of murine B16-F10 melanoma cells; Table S3: Expression levels of enzymes involved in sphingolipid metabolism in B16-F10 cells; Table S4: RT-qPCR analysis of the expression of tumor infiltrate markers and immune checkpoints in B16-F10 tumor grafts; Figure S1: Galca does not affect melanocyte differentiation in zebrafish; Figure S2: Galc downregulation does not affect cell cycle distribution and cell death in B16-F10 cells; Figure S3: The neutral sphingomyelinase inhibitor GW4869 increases the tumorigenic activity of shGALC-B16-F10 cells; Figure S4: Inhibition of the tumorigenic activity in shGALC-bis-B16-F10 cells; Figure S5: Public data mining of GALC expression in human melanoma; Figure S6: Public data mining of SMPD3 expression in human melanoma.

Single file with supplemental figures, methods, tables, legends: Figure S1: Effects of FGF blockade in MM; Figure S2: FGF inhibition induces oxidative stress-mediated apoptosis in MM cells; Figure S3: Mitochondrial oxidative stress is responsible for the antitumor activity exerted in vivo by FGF inhibition; Figure S4: Oxidative stress-induced apoptosis following FGF inhibition is c-Myc-dependent; Figure S5: Western blot analysis for caspase 3 activation in PBMCs compared to NSC12-sensitive patient-derived MM cells treated with NSC12 for 12 hours; Figure S6: Effects of FGF inhibition in BTZ-resistant KMS-11 cells; Figure S7: High doses of BTZ hamper basal and NSC12-induced c-Myc degradation; Table S1: List of Log2 2-fold down- or upregulated genes in KMS-11 cells after 6 and 12 hours of NSC12 6μM treatment; Table S2: Patient-derived MM cells treated with NSC12; Reagent table.

Simulation and treatment of TRAMP mice treated with enzalutamide, cabazitaxel and the combination

Supplementary Tables with parameters

Supplementary Figure Legends S1-S16