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To examine the relationship between assisting hand use in bimanual activities and children's self-care activities and task performance.We retrospectively analysed daily functioning (Pediatric Evaluation of Disability Inventory [PEDI]) and bimanual performance (Assisting Hand Assessment [AHA]) data from the assessment of 112 children (mean age: 8 years 10 months [SD 2 years 1 month], range 3 years 7 months-17 years 4 months; 66 males, 46 females) with unilateral spastic cerebral palsy (CP). We used Rasch analysis to examine the relationship between individual item scores from the AHA and the self-care items (functional skills, caregiver assistance) from the PEDI.Most self-care functional skills and caregiver-assisted tasks were located on the middle of the unidimensional continuum. These items showed similar levels of difficulty as the items from the AHA related to the effective coordination of two hands, appropriate pace, and use of the assisting hand to stabilize and release objects, as well as variations in arm movements.The distribution of the PEDI self-care and AHA items along the unidimensional continuum illustrates the relationship between assisting hand use and self-care bimanual performance. Interpretation of the items' locations on the hierarchical unidimensional continuum may be helpful to therapists' clinical reasoning and suggest intervention goals to improve the hand function and daily functioning of children with unilateral spastic CP. Such an application needs further investigation.

Chronic lymphocytic leukaemia (CLL) has a highly variable clinical course. In addition to biological factors, socioeconomic factors and health system characteristics may influence CLL outcome. Data from the Brazilian Registry of CLL were analyzed to compare clinical and treatment-related characteristics in patients with CLL, from public or private institutions. A total of 3326 patients from 43 centres met the eligibility criteria, of whom 81% were followed up at public hospitals and 19% at private hospitals. The majority were male (57%), with a median age of 65 years. Comparing public and private hospitals, patients in public hospitals were older, had more advanced disease at diagnosis, and more frequently had elevated creatinine levels. All investigated prognostic markers were evaluated more often in private hospitals. First-line treatment was predominantly based on chlorambucil in 41% of the cases and fludarabine in 38%. Anti-CD20 monoclonal antibody was used in only 36% of cases. In public hospitals, significantly fewer patients received fludarabine-based regimens and anti-CD20 monoclonal antibodies. Patients from public hospitals had significantly worse overall survival (71% vs. 90% for private hospitals

The development and implementation of transition services for adolescents with disabilities should incorporate perceptions of their needs and interests. The aim of the study was to understand the concerns of adolescents with physical disabilities during adolescence and their expectations regarding adulthood to help plan a transition programme in Brazil.This is a qualitative study, using a phenomenological approach. Eight adolescents with physical disabilities (seven with cerebral palsy, one with muscular dystrophy), aged between 15 and 17 years, participated in two focus groups. Prior to the conduction of the groups, clinicians selected topics related to adolescence and the transition to adulthood, based on their professional experience and available literature. During the focus groups, illustrative images of each topic were presented to the participants. Each adolescent was asked to select five topics that he/she considered important to be discussed in a future transition programme. The participants justified their individual choices and, in groups, reached a consensus on the groups' priorities. This strategy was chosen to motivate the discussion among the participants and to explore their concerns regarding adolescence and transition to adulthood. The focus groups were audio recorded and transcribed for content analysis.Three themes emerged from the content analysis: (1) "Adolescents and their social relationships," (2) "Identity formation: self-awareness and development of autonomy," and (3) "What about adulthood?"The themes revealed conflicts between the adolescents' desire to achieve independence and autonomy and the awareness of their limitations. The interpretation of the results helped structuring the actions of the Adolescence in Focus Programme, with two main actions: promotion of the adolescent's functional performance in daily living activities and assistance with their identity formation and preparation for adulthood.

This article examines experimentally and numerically the flexural performance of low-strength reinforced concrete (RC) beams strengthened using near-surface mounted (NSM) carbon fibre reinforced polymer (CFRP) rods. Five RC rectangular beams were tested in four-point bending until failure. Four of these beams were strengthened using Bottom NSM (BNSM) or Side NSM (SNSM) rods. The results are discussed in terms of observed damage, load capacity, and midspan deflection. It is shown that the SNSM strengthening solution enhanced the cracking load of the beams by up to 19%. Similarly, the yield and ultimate load-carrying capacities of the strengthened beams increased by up to 31% and 64%, respectively. It is also shown that moment-curvature and FE approaches predict well the deflections of the strengthened RC beams within 20% and 10% of accuracy at failure. The results from nonlinear Finite Element (FE) analyses showed a better agreement with the experimental results up to failure (within a 10% of accuracy). For the beams presented in this study, the crack widths calculated by Eurocode 2 match reasonably well the measured values.

Amazonian environments are being degraded by modern industrial and agricultural activities at a pace far above anything previously known, imperiling its vast biodiversity reserves and globally important ecosystem services. The most substantial threats come from regional deforestation, because of export market demands, and global climate change. The Amazon is currently perched to transition rapidly from a largely forested to a nonforested landscape. These changes are happening much too rapidly for Amazonian species, peoples, and ecosystems to respond adaptively. Policies to prevent the worst outcomes are known and must be enacted immediately. We now need political will and leadership to act on this information. To fail the Amazon is to fail the biosphere, and we fail to act at our peril.

Summary Background Owing to increasing remission rates, the management of patients with rheumatoid arthritis in sustained remission is of growing interest. The Rheumatoid Arthritis in Ongoing Remission (RETRO) study investigated tapering and withdrawal of disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis in stable remission to test whether remission could be retained without the need to take DMARD therapy despite an absence of symptoms. Methods RETRO was an investigator-initiated, multicentre, prospective, randomised, controlled, open-label, parallel-group phase 3 trial in patients aged at least 18 years with rheumatoid arthritis for at least 12 months before randomisation who were in sustained Disease Activity Score using 28 joints with erythrocyte sedimentation rate (ESR) remission (score ClinicalTrials.gov ( NCT02779114 ). Findings Between May 26, 2010, and May 29, 2018, 303 patients were enrolled and allocated to continue (n=100), taper (n=102), or stop DMARDs (n=101). 282 (93%) of 303 patients were analysed (93 [93%] of 100 for continue, 93 [91%] of 102 for taper, and 96 [95%] of 101 for stop). Remission was maintained at 12 months by 81·2% (95% CI 73·3–90·0) in the continue group, 58·6% (49·2–70·0) in the taper group, and 43·3% (34·6–55·5) in the stop group (p=0·0005 with log-rank test for trend). Hazard ratios for relapse were 3·02 (1·69–5·40; p=0.0003) for the taper group and 4·34 (2·48–7·60; p Interpretation Reducing antirheumatic drugs in patients with rheumatoid arthritis in stable remission is feasible, with maintenance of remission occurring in about half of the patients. Because relapse rates were significantly higher in patients who tapered or stopped antirheumatic drugs than in patients who continued with a 100% dose, such approaches will require tight monitoring of disease activity. However, remission was regained after reintroduction of antirheumatic treatments in most of those who relapsed in this study. These results might help to prevent overtreatment in a substantial number of patients with rheumatoid arthritis. Funding None.

Recently, there has been an increase in the development of transition services for adolescents with cerebral palsy (CP). These studies have emphasized the importance of addressing parents' needs during their children's adolescence.To understand how parents experience adolescence and transition to adulthood of their adolescents with CP and to identify relevant components for the development of a service for families.A qualitative study was conducted with 18 families of adolescents with CP. Caregivers were purposely recruited from the Adolescence in Focus Program, a transition program. Individual interviews were conducted using a semistructured script. Then, the caregivers were invited to participate in focus groups. The interviews and focus groups were recorded and transcribed for content analysis.Three categories emerged: "The onset of adolescence"; "What will our future be?"; and "Support and services: paths to follow". The adolescents' behavioral changes seemed to be intensified by their restricted social participation. The parents reported the desire for their adolescents to become independent in daily activities. Regarding their own future, they aimed to reestablish the occupational roles that were interrupted.Information from this study guided the design of a program for families regarding content, format and outcomes.

The upgrade of the CMS experiment for the high luminosity operation of the LHC comprises the replacement of the current endcap calorimeter by a high granularity sampling calorimeter (HGCAL). The electromagnetic section of the HGCAL is based on silicon sensors interspersed between lead and copper (or copper tungsten) absorbers. The hadronic section uses layers of stainless steel as an absorbing medium and silicon sensors as an active medium in the regions of high radiation exposure, and scintillator tiles directly readout by silicon photomultipliers in the remaining regions. As part of the development of the detector and its readout electronic components, a section of a silicon-based HGCAL prototype detector along with a section of the CALICE AHCAL prototype was exposed to muons, electrons and charged pions in beam test experiments at the H2 beamline at the CERN SPS in October 2018. The AHCAL uses the same technology as foreseen for the HGCAL but with much finer longitudinal segmentation. The performance of the calorimeters in terms of energy response and resolution, longitudinal and transverse shower profiles is studied using negatively charged pions, and is compared to GEANT4 predictions. This is the first report summarizing results of hadronic showers measured by the HGCAL prototype using beam test data., Comment: Accepted for publication by JINST

Biochemical, serological, and molecular methods have been developed for the laboratory diagnosis of diseases caused by

The Wnt/β-catenin signaling pathway dictates cell proliferation and differentiation during embryonic development and tissue homeostasis. Its deregulation is associated with many pathological conditions, including neurodegenerative disease, frequently downregulated. The lack of efficient treatment for these diseases, including Alzheimer’s disease (AD), makes Wnt signaling an attractive target for therapies. Interestingly, novel Wnt signaling activating compounds are less frequently described than inhibitors, turning the quest for novel positive modulators even more appealing. In that sense, natural compounds are an outstanding source of potential drug leads. Here, we combine different experimental models, cell-based approaches, neuronal culture assays, and rodent behavior tests with Xenopus laevis phenotypic analysis to characterize quercitrin, a natural compound, as a novel Wnt signaling potentiator. We find that quercitrin potentiates the signaling in a concentration-dependent manner and increases the occurrence of the Xenopus secondary axis phenotype mediated by Xwnt8 injection. Using a GSK3 biosensor, we describe that quercitrin impairs GSK3 activity and increases phosphorylated GSK3β S9 levels. Treatment with XAV939, an inhibitor downstream of GSK3, impairs the quercitrin-mediated effect. Next, we show that quercitrin potentiates the Wnt3a-synaptogenic effect in hippocampal neurons in culture, which is blocked by XAV939. Quercitrin treatment also rescues the hippocampal synapse loss induced by intracerebroventricular injection of amyloid-β oligomers (AβO) in mice. Finally, quercitrin rescues AβO-mediated memory impairment, which is prevented by XAV939. Thus, our study uncovers a novel function for quercitrin as a Wnt/β-catenin signaling potentiator, describes its mechanism of action, and opens new avenues for AD treatments.

Sepsis survivors show long-term impairments, including alterations in memory and executive function. Evidence suggests that systemic inflammation contributes to the progression of Alzheimeŕs disease (AD), but the mechanisms involved in this process are still unclear. Boosted (trained) and diminished (tolerant) innate immune memory has been described in peripheral immune cells after sepsis. However, the occurrence of long-term innate immune memory in the post-septic brain is fully unexplored. Here, we demonstrate that sepsis causes long-lasting trained innate immune memory in the mouse brain, leading to an increased susceptibility to Aβ oligomers (AβO), central neurotoxins found in AD. Hippocampal microglia from sepsis-surviving mice shift to an amoeboid/phagocytic morphological profile when exposed to low amounts of AβO, and this event was accompanied by the upregulation of several pro-inflammatory proteins (IL-1β, IL-6, INF-γ and P2X7 receptor) in the mouse hippocampus, suggesting that a trained innate immune memory occurs in the brain after sepsis. Brain exposure to low amounts of AβO increased microglial phagocytic ability against hippocampal synapses. Pharmacological blockage of brain phagocytic cells or microglial depletion, using minocycline and colony stimulating factor 1 receptor inhibitor (PLX3397), respectively, prevents cognitive dysfunction induced by AβO in sepsis-surviving mice. Altogether, our findings suggest that sepsis induces a long-lasting trained innate immune memory in the mouse brain, leading to an increased susceptibility to AβO-induced neurotoxicity and cognitive impairment.

Examinar a relação entre o uso da mão de assistência em atividades bimanuais e o desempenho de crianças nas atividades e tarefas de autocuidado. MÉTODO: Analisamos retrospectivamente dados da funcionalidade diária (Inventário de Avaliação Pediátrica de Incapacidade [PEDI]) e do desempenho bimanual (Avaliação da Mão de Assistência [AHA]) de 112 crianças (idade média: 8 anos 10 meses [DP 2 anos 1 mês], amplitude 3 anos 7 meses-17 anos 4 meses; 66 meninos, 46 meninas) com paralisia cerebral (PC) unilateral espástica. Nós usamos análise Rasch para examinar a relação entre os escores individuais nos itens do AHA e nos itens de autocuidado (habilidades funcionais e assistência do cuidador) do PEDI.A maioria das habilidades funcionais e das tarefas de assistência do cuidador de autocuidado ficaram localizadas no meio do contínuo unidimensional. Estes itens apresentaram níveis de dificuldade semelhantes aos itens do AHA relacionados à coordenação efetiva das duas mãos, cadência, e uso da mão de assistência para estabilizar e soltar objetos, bem como variações nos movimentos dos braços. INTERPRETAÇÃO: A distribuição dos itens de autocuidado do PEDI e itens do AHA ao longo do contínuo unidimensional ilustra a relação entre o uso da mão de assistência e o desempenho bimanual em autocuidado. Interpretação sobre a localização dos itens na hierarquia do contínuo unidimensional pode ajudar no raciocínio clínico dos terapeutas e na sugestão de objetivos de intervenção para melhorar a função manual e a funcionalidade diária de crianças com PC unilateral espástica. Tais aplicações necessitam de investigação futura.

AIM The aim of this study was to compare OsiriX software with the previous published Medical Image Analysis Framework (MIAF) method to assess the volume of erosion in patients with rheumatoid arthritis (RA). METHODS Forty RA patients underwent high-resolution peripheral quantitative computed tomography scans of the second and third metacarpophalangeal joints, and thirty-four patients with any bone erosion were enrolled. Two techniques were applied to erosion evaluation: (a) semi-automated MIAF software, and (b) semi-automated segmentation by free open-source Digital Imaging and Communications in Medicine viewer, OsiriX software. MIAF has been published before, but this is the first time that OsiriX has been used in this way in rheumatology. Bland & Altman plots described agreement between methods. RESULTS Forty-eight erosions from 34 patients were analyzed. Mean age was 40.74 ± 5.32 years and mean disease duration was 10.68 ± 4.96 years. Both methods demonstrated a strong correlation regarding erosion volume (r = 0.96, P

Arbutus unedo L. is a Mediterranean species used for fruit production, it is tolerant to drought and shows regeneration ability following forest fires. Mycorrhizal plants with Tuber borchii add resilience and value. This study aims to test the effect of quercetin on mycorrhizal synthesis between T. borchii and A. unedo. Two genotypes selected for fruit production and hydric stress tolerance, were micropropagated for mycorrhizal synthesis, accomplished during ex vitro rooting in perlite, using lyophilized spores of T. borchii suspended in culture media with different quercetin levels (0–10 µM). Six months after inoculation, plants were transferred to pots and maintained in nursery. Ten and 12 months after inoculation, roots were morphological examined and molecularly characterized using ITS1-5.8SITS2 rDNA region and specific primers. Results showed that mycorrhizae establishment was dependent on studied factors (genotype, quercetin level, and culture medium) and their interaction (genotype X culture medium). Quercetin levels up to 2.0 µM favored mycorrhizae establishment and plant growth, although levels superior to 4 µM showed a toxic effect. Quercetin showed to be an efficient factor on inducing mycorrhiza thriving independent of the genotype. Morphological observations and molecular analysis confirmed the permanence of the fungus association 10 and 12 months after inoculation.

Phytophthora cinnamomi is a threat to chestnut fruit production. For improving resistance to this pathogen, a breeding program was implemented based on controlled crosses between Castanea species (Europe x Asia), using the latter as donor of resistant genes. The offspring with altered susceptibility to Phytophthora have been micropropagated. Plantlets were acclimatized to obtain copies of each genotype for phenotyping to Phytophthora susceptibility through inoculation tests. In this work, different methods of in vitro conservation, slow-growth storage and synthetic seed, during 9 and 12 months (at 4 oC, darkness) were compared. For slow-growth storage, different types and concentrations of carbon sources (sucrose and mannitol at 0.09, 0.16, 0.22 M) were compared. Conversely, for synseeds, nodal segments were encapsulated using different concentrations of Na-alginate (2.75, 3%) and released in a solution of CaCl22H2O (50, 75, 100 mM). For conservation, three conditions were tested: empty tubes; tubes filled (15 mL) with sterile distilled water, and tubes with a 30% glycerol solution. Both methods tested were found suitable for medium-term conservation (12 months). For slow-growth storage, the best results of survival (93.3%) and multiplication rate (2.10, at 2nd subculture) were achieved with 0.22 M sucrose. To the best of our knowledge, our studies show for the first time that the storage of the synseeds in tubes with sterile distilled water was the most effective method for conservation, allowing higher survival (97.5%) and germination (92.5%). The use of the highest concentration of Na-alginate demonstrated to promote the multiplication rate (3.18, at 2nd subculture).

Expository approaches in project management education do not seem to be engaging engineering students. Although the students acquire remarkable theoretical knowledge throughout their coursework, they lack transferable competences, such as soft skills, which are scarcely attended in the teaching of project management. Generation Z's characteristics differ from previous generations and should be considered in new project management education approaches and methods. This article reviews the project management competencies, Generation Z profile, and teaching methods trends reported in the literature. It presents a study involving 147 engineering students, through a self-report questionnaire, to explore their profile's self-awareness and compare it with the literature. A correlational study links the Generation Z's personality traits with project management soft skills. Findings reveal interesting personality characteristics of Generation Z engineering students for the project management field. However, this sample showed low recognition of their individualism, less personal relationships, and did not value their creative potential. There were also differences in Electronic, Electrical, and Computer Science engineering students, namely, lower emotional intelligence. Some highlighted traits have a significant effect on critical project management soft skills. Other soft skills were not supported in personality traits. This work suggests implications for re-think educational approaches to Generation Z engineering students.

Normal-to-malignant transformation is a poorly understood process associated with cellular biomechanical properties. These are strongly dependent on the dynamical behaviour of water, known to play a fundamental role in normal cellular activity and in the maintenance of the three-dimensional architecture of the tissue and the functional state of biopolymers. In this study, quasi-elastic neutron scattering was used to probe the dynamical behaviour of water in human cancer specimens and their respective surrounding normal tissue from breast and tongue, as an innovative approach for identifying particular features of malignancy. This methodology has been successfully used by the authors in human cells and was the first study of human tissues by neutron scattering techniques. A larger flexibility was observed for breast

Cognitive dysfunction is often reported in post-COVID patients, but its underlying mechanisms remain unknown. While some evidence indicate that SARS-CoV-2 can reach and directly impact the brain, others suggest viral neuroinvasion as a rare event. Independently of brain viral infection, the ability of SARS-CoV-2 spike (S) protein to cross the BBB and reach memory-related brain regions has already been shown. Here, we demonstrate that brain infusion of S protein in mice induces late cognitive impairment and increases serum levels of neurofilament light chain (NFL), which recapitulates post-COVID features. Neuroinflammation, hippocampal microgliosis and synapse loss are induced by S protein. Increased engulfment of hippocampal presynaptic terminals late after S protein brain infusion were found to temporally correlate with cognitive deficit in mice. Blockage of TLR4 signaling prevented S-associated detrimental effects on synapse and memory loss. In a cohort of 86 patients recovered from mild COVID-19, genotype GG TLR4 -2604G>A (rs10759931) was associated with poor cognitive outcome. Collectively, these findings indicate that S protein directly impacts the brain and suggest that TLR4 is a potential target to prevent post-COVID cognitive dysfunction.One Sentence SummaryTLR4 mediates long-term cognitive impairment in mice and its genetic variant increases the risk of poor cognitive outcome in post-COVID patients.

RoundUp® (RUp) is a comercial formulation containing glyphosate (N-(phosphono-methyl) glycine), and is the world’s leading wide-spectrum herbicide used in agriculture. Supporters of the broad use of glyphosate-based herbicides (GBH) claim they are innocuous to humans, since the active compound acts on the inhibition of enzymes which are absent in human cells. However, the neurotoxic effects of GBH have already been shown in many animal models. Further, these formulations were shown to disrupt the microbiome of different species. Here, we investigated the effects of a lifelong exposure to low doses of the GBH-RUp on the gut environment, including morphological and microbiome changes. We also aimed to determine whether exposure to GBH-RUp could harm the developing brain and lead to behavioral changes in adult mice. To this end, animals were exposed to GBH-RUp in drinking water from pregnancy to adulthood. GBH-RUp-exposed mice had no changes in cognitive function, but developed impaired social behavior and increased repetitive behavior. GBH-Rup-exposed mice also showed an activation of phagocytic cells (Iba-1–positive) in the cortical brain tissue. GBH-RUp exposure caused increased mucus production and the infiltration of plama cells (CD138-positive), with a reduction in phagocytic cells. Long-term exposure to GBH-RUp also induced changes in intestinal integrity, as demonstrated by the altered expression of tight junction effector proteins (ZO-1 and ZO-2) and a change in the distribution of syndecan-1 proteoglycan. The herbicide also led to changes in the gut microbiome composition, which is also crucial for the establishment of the intestinal barrier. Altogether, our findings suggest that long-term GBH-RUp exposure leads to morphological and functional changes in the gut, which correlate with behavioral changes that are similar to those observed in patients with neurodevelopmental disorders.

A Internet das Coisas para Cidades Inteligentes possibilita um melhor uso dos recursos e serviços. Porém, os desafios tecnológicos para a criação de sistemas computacionais eficientes aumentam devido ao número e complexidade das interações. Este artigo propõe distribuir as entidades do Paradigma Orientado a Notificações (PON) por meio de uma arquitetura publicação/assinatura com o protocolo MQTT. O desempenho do PON e do paradigma de programação orientado a objetos são comparados em uma aplicação genérica de Internet das Coisas. Os resultados mostram que ao distribuir as entidades do PON é possível reduzir o tempo de execução, processamento e resposta da aplicação ao custo de um maior uso de memória.

RoundUp

Imaging is essential for the assessment of bone and inflammatory joint diseases. There are several imaging techniques available that differ regarding resolution, radiation exposure, time expending,...

Sarcopenia is characterized by progressive loss of skeletal muscle mass, which results in decreased muscle strength, functional impairment, and increased risk of death. Few studies have performed a concomitant evaluation of clinical, laboratory, and body composition variables to accurately determine the contribution of each parameter to low muscle mass (LMM) in older subjects. This study aimed to identify risk factors (clinical, laboratory parameters, BMD, and body composition by DXA including visceral fat) for LMM in a prospective cohort of older Brazilian women.A total of 408 women aged ≥65 yr from the São Paulo AgeingHealth study were evaluated with clinical data, laboratory bone tests, BMD, and body composition by DXA using Hologic QDR 4500A equipment. Risk factors were measured at baseline (2005-2007). After a follow-up of 4.3 ± 0.8 yr, subjects were classified according to the LMM definition of the Foundation for the National Institutes of Health criteria. LMM was defined when appendicular lean mass divided by body mass index was less than 0.512. Multivariate logistic regression models were used to identify independent risk factors for LMM.At the end of follow-up, 116 women (28.4%) had LMM. Age averages were 73.3 ± 4.9 yr in the LMM group and 72.5 ± 4.5 yr in the normal group (p = 0.11). Mean BMI was 30.6 ± 5.2 kg/mFalls, high TSH, low creatinine, and high VAT were risk factors for LMM in older women. More attention should be paid to these factors, since they are potentially reversible with adequate intervention.

A bimetallic vanadium and niobium oxide catalyst using alumina as support was developed for the conversion of crude glycerol from biodiesel production into formic acid. The high dispersion of the active oxide phase combined with the presence of acid and redox active centers resulted in a high glycerol conversion (>90% for 25 h) with a good selectivity for formic acid (∼55%). This process is the first example of a heterogeneous liquid-phase process for the conversion of crude glycerol to formic acid, which is an important chemical intermediate currently derived from petroleum feedstock.

Purpose The purpose of this paper is to ascertain the extent to which knowledge management (KM), customer satisfaction (CS) and organizational image (OI) discriminate quality-certified municipalities from non-certified ones (ISO 9001). Design/methodology/approach An empirical study was carried out involving 81 Portuguese municipalities (40 certified, 41 non-certified), paired in a random sampling procedure. The Knowledge Management Questionnaire (n=1,372 municipality employees), the Customer Satisfaction Questionnaire and the Organizational Image Questionnaire (n=3,096 residents) were applied. Multiple discriminant analysis was performed. Findings The results indicate that certified and non-certified municipalities are distinct based on a function that considers KM (competitive orientation and formal KM practices), CS (intangible and tangible factors) and OI (favorable image). Research limitations/implications The findings need further validation in other countries. However, the results highlight the importance of quality certification for both employees and residents. Practical implications The results encourage local public administration organizations to introduce and maintain quality certification. Originality/value This research is the only one, to the authors’ knowledge, that simultaneously explores organizational processes of KM, CS and OI in local public administration. The sampling procedure and the information from diverse data sources are unique contributions. The conclusions may aid practitioners and scholars in understanding these organizational phenomena in the context of quality-certified and quality non-certified municipalities.

Although the benefits of moderate intake of red wine in decreasing incidence of cardiovascular diseases associated to hypercholesterolemia are well recognized, there are still widespread misconceptions about its effects on the hypercholesterolemia-related cognitive impairments. Herein we investigated the putative benefits of regular red wine consumption on cognitive performance of low-density lipoprotein receptor knockout (LDLr-/-) mice, an animal model of familial hypercholesterolemia, which display cognitive impairments since early ages. The red wine was diluted into the drinking water to a final concentration of 6% ethanol and was available for 60 days for LDLr-/- mice fed a normal or high-cholesterol diet. The results indicated that moderate red wine consumption did not alter locomotor parameters and liver toxicity. Across multiple cognitive tasks evaluating spatial learning/reference memory and recognition/identification memory, hypercholesterolemic mice drinking red wine performed significantly better than water group, regardless of diet. Additionally, immunofluorescence assays indicated a reduction of astrocyte activation and lectin stain in the hippocampus of LDLr-/- mice under consumption of red wine. These findings demonstrate that the moderate consumption of red wine attenuates short- and long-term memory decline associated with hypercholesterolemia in mice and suggest that it could be through a neurovascular action.

Since March 2020, after the World Health Organization (WHO) officially declared COVID-19 a pandemic

Zika virus (ZIKV) infection became a worldwide concern due to its correlation with the development of microcephaly and other neurological disorders. ZIKV neurotropism is well characterized, but the role of peripheral viral amplification to brain infection remains unknown. Here, we found that ZIKV replicates in human primary skeletal muscle myoblasts, impairing its differentiation into myotubes but not interfering with the integrity of the already-formed muscle fibers. Using mouse models, we showed ZIKV tropism to muscle tissue either during embryogenesis after maternal transmission or when infection occurred after birth. Interestingly, ZIKV replication in the mouse skeletal muscle started immediately after ZIKV inoculation, preceding viral RNA detection in the brain and causing no disruption to the integrity of the blood brain barrier, and remained active for more than 2 weeks, whereas replication in the spleen and liver were not sustained over time. In addition, ZIKV infection of the skeletal muscle induces necrotic lesions, inflammation, and fiber atrophy. We also found a reduction in the expression of regulatory myogenic factors that are essential for muscle repair after injury. Taken together, our results indicate that the skeletal muscle is an early site of viral amplification and lesion that may result in late consequences in muscle development after ZIKV infection. IMPORTANCE Zika Virus (ZIKV) neurotropism and its deleterious effects on central nervous system have been well characterized. However, investigations of the initial replication sites for the establishment of infection and viral spread to neural tissues remain underexplored. A complete description of the range of ZIKV-induced lesions and others factors that can influence the severity of the disease is necessary to prevent ZIKV’s deleterious effects. ZIKV has been shown to access the central nervous system without significantly affecting blood-brain barrier permeability. Here, we demonstrated that skeletal muscle is an earlier site of ZIKV replication, contributing to the increase of peripheral ZIKV load. ZIKV replication in muscle promotes necrotic lesions and inflammation and also impairs myogenesis. Overall, our findings showed that skeletal muscle is involved in pathogenesis and opens new fields in the investigation of the long-term consequences of early infection.

Nannochloropsis oceanica can accumulate lipids and is a good source of polar lipids, which are emerging as new value-added compounds with high commercial value for the food, nutraceutical, and pharmaceutical industries. Some applications may limit the extraction solvents, such as food applications that require safe food-grade solvents, such as ethanol. However, the effect of using ethanol as an extraction solvent on the quality of the extracted polar lipidome, compared to other more traditional methods, is not yet well established. In this study, the polar lipid profile of N. oceanica extracts was obtained using different solvents, including chloroform/methanol (CM), dichloromethane/methanol (DM), dichloromethane/ethanol (DE), and ethanol (E), and evaluated by modern lipidomic methods using LC-MS/MS. Ultrasonic bath (E + USB)- and ultrasonic probe (E + USP)-assisted methodologies were implemented to increase the lipid extraction yields using ethanol. The polar lipid signature and antioxidant activity of DM, E + USB, and E + USP resemble conventional CM, demonstrating a similar extraction efficiency, while the DE and ethanol extracts were significantly different. Our results showed the impact of different extraction solvents in the polar lipid composition of the final extracts and demonstrated the feasibility of E + USB and E + USP as safe and food-grade sources of polar lipids, with the potential for high-added-value biotechnological applications.

Nannochloropsis oceanica can accumulate lipids and is a good source of polar lipids, which are emerging as new value-added compounds with high commercial value for the food, nutraceutical, and pharmaceutical industries. Some applications may limit the extraction solvents, such as food applications that require safe food-grade solvents, such as ethanol. However, the effect of using ethanol as an extraction solvent on the quality of the extracted polar lipidome, compared to other more traditional methods, is not yet well established. In this study, the polar lipid profile of N. oceanica extracts was obtained using different solvents, including chloroform/methanol (CM), dichloromethane/methanol (DM), dichloromethane/ethanol (DE), and ethanol (E), and evaluated by modern lipidomic methods using LC-MS/MS. Ultrasonic bath (E + USB)- and ultrasonic probe (E + USP)-assisted methodologies were implemented to increase the lipid extraction yields using ethanol. The polar lipid signature and antioxidant activity of DM, E + USB, and E + USP resemble conventional CM, demonstrating a similar extraction efficiency, while the DE and ethanol extracts were significantly different. Our results showed the impact of different extraction solvents in the polar lipid composition of the final extracts and demonstrated the feasibility of E + USB and E + USP as safe and food-grade sources of polar lipids, with the potential for high-added-value biotechnological applications.

The LB Building 6 is the main logistic building of the Total Agility Logistic Co. Ltd located in Bang Phi district, Samut-Prakan province, Thailand. The building consists of a 2 storey steel structure having steel beams with a typical span of 6.0 m supported by reinforced columns. After a few months of service, cracking and spalls was found on the concrete overlay on the 2nd floor. Preliminary investigations were first performed by the building engineer and it was reported that deflections occurred at the 1-ton forklift moving path zone. Therefore, the capacity of structural elements in the building had to be re-assessed and field measurements of vibration levels were also taken during the peak operation period. To reduce the vibration level as well as deformation of the floor under normal operation, a structural strengthening intervention was made by adding additional steel beams under the hollow core slab as a span shortening technique. Field measurements have shown that the vibrations of the strengthened concrete slab reduced by up to 35% compared to the pre-strengthening measurements, thus confirming the effectiveness of the strengthening intervention. The work reported in this paper also sets the scene for identifying the major decisions for a design engineer starting from on-site inspection to the post-construction supervision.

To evaluate premenopausal women with longstanding rheumatoid arthritis (RA) for potential associations between parameters of localized bone involvement and parameters of systemic bone involvement in the affected joints.Eighty consecutively evaluated premenopausal women with RA were included in the study, along with 160 healthy female control subjects who were matched to the patients by age and body mass index. Volumetric bone mineral density (vBMD), bone microarchitecture, and finite elements of biomechanical bone strength (bone stiffness and estimated failure load) at the distal radius and distal tibia were analyzed by high-resolution peripheral quantitative computed tomography (HR-pQCT) in patients with RA compared to healthy controls. In addition, in patients with RA, localized bone involvement in the metacarpophalangeal and proximal interphalangeal joints was analyzed by HR-pQCT, to identify bone erosions and osteophytes.Among the 80 premenopausal women with longstanding RA, the mean ± SD age was 39.4 ± 6.7 years and mean ± SD disease duration was 9.8 ± 5.3 years. Trabecular and cortical bone parameters and bone strength at the distal radius and distal tibia were all impaired in patients with RA compared to healthy controls (each P 0.05). In total, 75% of RA patients had evidence of bone erosions, and 41.3% of RA patients had detectable osteophytes on HR-pQCT. RA patients with bone erosions, as compared to RA patients without bone erosions, had lower cortical vBMD (at the distal radius, mean ± SD 980 ± 72 mg HA/cmThe findings show that premenopausal women with longstanding RA have systemic bone fragility at peripheral joint sites. Moreover, the presence of bone erosions is mainly associated with cortical bone fragility at the distal radius and tibia, and presence of osteophytes is associated with repair of trabecular bone at the distal radius.

Background Although produced by several types of tumours, the role of serotonin on cancer biology is yet to be understood. Methods The effects of serotonin (5-HT) on human breast cancer cells proliferation, signalling pathways and metabolic profile were evaluated by cytometry, western blotting, qPCR, enzymology and confocal microscopy. Results Our results revealed that incubation of MCF-7 cells with 10 µM 5-HT increased cell growth rate by 28%, an effect that was prevented by the 5-HTR2A/C antagonist, ketanserin. Conversely, increasing concentrations of 5-HT promoted glucose consumption and lactate production by MCF-7 cells. We also showed that increased glucose metabolism is provoked by the upregulation of pyruvate kinase M2 (PKM2) isoform through 5-HTR2A/C-triggered activation of Jak1/STAT3 and ERK1/2 subcellular pathways. However, we noticed a decrease in the rate of produced lactate per consumed glucose as a function of the hormone concentration, suggesting a disruption of the Warburg effect. The latter effect is due to 5-HTR2A/C-dependent mitochondrial biogenesis and metabolism, which is triggered by adenylyl cyclase/PKA, enhancing the oxidation of lactate within these cells. Conclusions We showed that serotonin, through 5-HTR2A/C, interferes with breast cancer cells proliferation and metabolism by triggering two distinct signalling pathways: Jak1/STAT3 that boosts glycolysis through upregulation of PKM2, and adenylyl cyclase/PKA that enhances mitochondrial biogenesis.

EP Figueiredo,1 JM Ribeiro,1 EK Nishio,1 S Scandorieiro,1 AF Costa,2 VF Cardozo,1 AG Oliveira,1 N Durán,2–4 LA Panagio,1 RKT Kobayashi,1 G Nakazato1 1Department of Microbiology, Center of Biological Sciences, Universidade Estadual de Londrina, Londrina, Paraná, Brazil; 2NanoBioss, Institute of Chemistry, Universidade Estadual de Campinas, Campinas, São Paulo, Brazil; 3Institute of Chemistry, Universidade Estadual de Campinas, Campinas, São Paulo, Brazil; 4LNNano (National Laboratory of Nanotecnology), CNPEM, Campinas, São Paulo, BrazilCorrespondence: G NakazatoDepartment of Microbiology, Center of Biological Sciences, Universidade Estadual de Londrina, Campus Universitário, CEP, Londrina 86055-990, Paraná, BrazilTel +55 43 3371 4396Fax +55 43 3371 4788Email gersonakazato@yahoo.com.brBackground: Multidrug-resistant bacteria such as extended-spectrum beta-lactamase (ESBL), Enterobacteriaceae, and methicillin-resistant Staphylococcus aureus (MRSA) pose a challenge to the human health care system. MRSA is among the major causes of hospital-acquired and community infections.Methods: Therefore, in the present study, we evaluated the antibacterial activity of silver nanoparticles synthesized by Fusarium oxysporum (AgNPbio) in combination with simvastatin against reference and multidrug-resistant bacterial strains.Results: Simvastatin showed a minimal inhibitory concentration (MIC) ranging from 0.062 to 0.25 mg mL−1 against MRSA. AgNPbio with a size of 77.68± 33.95 nm and zeta potential −34.6 ± 12.7 mV showed an MIC of 0.212 mg mL−1 against S. aureus including MRSA strains. The checkerboard assay and time-kill curves exhibited a synergistic effect of the simvastatin-AgNPbio combination on antibacterial activity against MRSA strains. The combination of simvastatin and AgNPbio demonstrated antibacterial activity against Escherichia coli producing ESBL. Scanning electron microscopy showed the formation of cell surface protrusions after treatment with AgNPbio and the formation of a large amorphous mass after treatment with simvastatin, both in MRSA.Conclusion: Our results indicate that the combination of AgNPbio and simvastatin could be a great future alternative in the control of bacterial infections, where, when combined with simvastatin, smaller doses of AgNPbio are required, with the same antibacterial activity.Keywords: antibacterial, metallic nanoparticles, multidrug-resistant bacterial, statins, synergism