Industry 4.0 is a new industrial paradigm that brings new challenges for workers as they have to actively collaborate with robots in an interconnected environment. The main purpose of this paper is to give a brief overview of how collaborative robots can be used to support human workers in Industry 4.0 manufacturing environments. The use of collaborative robots certainly brings many advantages as these machines enable more efficient product systems by supporting workers with both physical and cognitive tasks, as is the case of exoskeletons. On the other hand, human–robot interaction might also have some risks if human factors considerations are not well thought through throughout the process. Moreover, it becomes clear that the role that humans have been playing so far in a manufacturing environment is rapidly changing. Human workers will have to adapt to these new systems by acquiring and improving a set of skills that have sometime been neglected until nowadays.

Insufficient oxygen supply represents a relevant issue in several fields of human physiology and medicine. It has been suggested that the implantation of photosynthetic cells can provide oxygen to tissues in the absence of a vascular supply. This approach has been demonstrated to be successful in several in vitro and in vivo models; however, no data is available about their safety in human patients. Here, an early phase-1 clinical trial (ClinicalTrials.gov identifier: NCT03960164, https://clinicaltrials.gov/ct2/show/NCT03960164) is presented to evaluate the safety and feasibility of implanting photosynthetic scaffolds for dermal regeneration in eight patients with full-thickness skin wounds. Overall, this trial shows that the presence of the photosynthetic microalgae Chlamydomonas reinhardtii in the implanted scaffolds did not trigger any deleterious local or systemic immune responses in a 90 days follow-up, allowing full tissue regeneration in humans. The results presented here represent the first attempt to treat patients with photosynthetic cells, supporting the translation of photosynthetic therapies into clinics.

Establishing a node importance ranking is a problem that has attracted the attention of many researchers in recent decades. For unweighted networks where the edges do not have any attached weight, many proposals have been presented, considering local or global information of the networks. On the contrary, it occurs in undirected edge-weighted networks, where the proposals to address this problem have been more scarce. In this paper, a ranking method of node importance for undirected and edge-weighted is provided, generalizing the measure of line importance (DIL) based on the centrality degree proposed by Opsahl. The experimentation was done on five real networks and the results illustrate the benefits of our proposal.

Neuromodulation can profoundly impact the gain and polarity of postsynaptic changes in Hebbian synaptic plasticity. An emerging pattern observed in multiple central synapses is a pull–push type of control in which activation of receptors coupled to the G-protein Gs promote long-term potentiation (LTP) at the expense of long-term depression (LTD), whereas receptors coupled to Gq promote LTD at the expense of LTP. Notably, coactivation of both Gs- and Gq-coupled receptors enhances the gain of both LTP and LTD. To account for these observations, we propose a simple kinetic model in which AMPA receptors (AMPARs) are trafficked between multiple subcompartments in and around the postsynaptic spine. In the model AMPARs in the postsynaptic density compartment (PSD) are the primary contributors to synaptic conductance. During LTP induction, AMPARs are trafficked to the PSD primarily from a relatively small perisynaptic (peri-PSD) compartment. Gs-coupled receptors promote LTP by replenishing peri-PSD through increased AMPAR exocytosis from a pool of endocytic AMPAR. During LTD induction AMPARs are trafficked in the reverse direction, from the PSD to the peri-PSD compartment, and Gq-coupled receptors promote LTD by clearing the peri-PSD compartment through increased AMPAR endocytosis. We claim that the model not only captures essential features of the pull–push neuromodulation of synaptic plasticity, but it is also consistent with other actions of neuromodulators observed in slice experiments and is compatible with the current understanding of AMPAR trafficking.

Fear of contagion, together with the consequences of mitigation strategies, are often cited as causes of high levels of anxiety in the general population in the context of the COVID-19 pandemic. However, it is unclear whether published reports make it possible to distinguish between normal and pathological anxiety. We conducted a non-systematic, descriptive literature review on observational studies reporting the prevalence or frequency of anxiety symptoms in non-clinical settings published between July and December 2020. Seventy-six studies were included. Two were conducted through telephone contact while the remainder were conducted on the internet. Factors associated with greater presence/severity of anxiety symptoms were sociodemographic variables (e.g., age, gender, employment, place of residence, living conditions, marital status, and educational level). Thirty publications (39.4%) reported data on a comparison group, including samples of general populations from different geographic regions or in different periods. Only 16 studies (21%) included some estimation of the functional impairment of detected anxiety symptoms. Only seven of the studies that estimated functional impairment had comparison groups. None of the studies included in this review contain sufficient contextual or descriptive information to determine whether the reported high levels of anxiety are normal reactions of subjects in high-stress situations or actual psychiatric disorders.

Este artigo analisa e discute as produções acadêmicas da Educação Física sobre Educação Infantil a partir de uma breve apresentação e análise dos estudos que tomaram tal produção como tema de investigação. Em termos metodológicos se constitui numa revisão integrativa dos artigos, teses e dissertações que se propuseram a estudar a referida produção e estão disponíveis no Portal de Periódicos da CAPES, no Catálogo de Teses e Dissertações da CAPES e na Biblioteca Digital Brasileira de Teses e Dissertações (BDTD). Apresenta uma síntese e análise dos principais aspectos da produção que os estudos nos permitem conhecer, aponta algumas lacunas e indica algumas relações entre os referenciais teóricos que embasam as produções e as proposições apresentadas para a prática pedagógica da Educação com a Educação Infantil que vêm sendo sistematizadas. Conclui que, embora importante, a ênfase dada pelos estudos de revisão e estado da arte aos aspectos quantitativos e descritivos da produção tem dificultado uma compreensão mais abrangente dos discursos que são produzidos sobre a Educação Física na Educação Infantil.

To construct a sudden death risk score specifically for hypertension (HYSUD) patients with or without cardiovascular history.Data were collected from six randomized controlled trials of antihypertensive treatments with 8044 women and 17 604 men differing in age ranges and blood pressure eligibility criteria. In total, 345 sudden deaths (1.35%) occurred during a mean follow-up of 5.16 years. Risk factors of sudden death were examined using a multivariable Cox proportional hazards model adjusted on trials. The model was transformed to an integer system, with points added for each factor according to its association with sudden death risk.Antihypertensive treatment was not associated with a reduction of the sudden death risk and had no interaction with other factors, allowing model development on both treatment and placebo groups. A risk score of sudden death in 5 years was built with seven significant risk factors: age, sex, SBP, serum total cholesterol, cigarette smoking, diabetes, and history of myocardial infarction. In terms of discrimination performance, HYSUD model was adequate with areas under the receiver operating characteristic curve of 77.74% (confidence interval 95%, 74.13-81.35) for the derivation set, of 77.46% (74.09-80.83) for the validation set, and of 79.17% (75.94-82.40) for the whole population.Our work provides a simple risk-scoring system for sudden death prediction in hypertension, using individual data from six randomized controlled trials of antihypertensive treatments. HYSUD score could help assessing a hypertensive individual's risk of sudden death and optimizing preventive therapeutic strategies for these patients.

Children born from women with preeclampsia have alterations in cerebral neurovascular development and a high risk for developing cognitive alterations. Because cerebral blood vessels are critical components in cerebrovascular development, we evaluated the brain microvascular perfusion and microvascular reactivity (exposed to external stimuli of warm and cold) in pups born to preeclampsia-like syndrome based on the reduction of uterine perfusion (RUPP). Also, we evaluate the angiogenic proteomic profile in those brains. Pregnant mice showed a reduction in uterine flow after RUPP surgery (−40 to 50%) associated with unfavorable perinatal results compared to sham mice. Furthermore, offspring of the RUPP mice exhibited reduced brain microvascular perfusion at postnatal day 5 (P5) compared with offspring from sham mice. This reduction was preferentially observed in females. Also, brain microvascular reactivity to external stimuli (warm and cold) was reduced in pups of RUPP mice. Furthermore, a differential expression of the angiogenic profile associated with inflammation, extrinsic apoptotic, cancer, and cellular senescence processes as the primary signaling impaired process was found in the brains of RUPP-offspring. Then, offspring (P5) from preeclampsia-like syndrome exhibit impaired brain perfusion and microvascular reactivity, particularly in female mice, associated with differential expression of angiogenic proteins in the brain tissue.

Background:The location of the cricothyroid membrane plays a fundamental role in the scenario of a difficult airway in the non-ventilated/ non-intubated situation.With the use of ultrasound, the membrane can be located easily by trained operators.Material and Methods: 82 patients with morbid obesity were studied, as it is a population with a higher incidence of difficult intubation.First, an operator made a marking based on anatomical landmarks.A different ultrasound-trained operator located the cricothyroid membrane with US.The difference in millimeters between both measurements was compared.Results: In the 82 patients, 100% located the cricothyroid membrane by US.When comparing both techniques, a difference of 5.8 ± 3.2 mm (p > 0.05) was found.Conclusion: The use of ultrasound for the evaluation of the airway is a non-invasive and useful technique that allows the identification of the cricothyroid membrane.

Objective To examine the effects of d -tagatose or stevia preloads on carbohydrate metabolism markers after an oral glucose load, as well as subjective and objective appetite in women with insulin resistance (IR). Research design and methods Randomized controlled crossover study. Women with IR without T2DM (n = 33; aged 23.4 ± 3.8; BMI 28.1 ± 3.4 kg × m −2 ) underwent three oral glucose loads (3 h each) on three different days. Ten min before oral glucose load, volunteers consumed a preload of 60 mL water (control), 60 mL water with stevia (15.3 mg), or d -tagatose (5000 mg). Serum glucose and C-peptide were evaluated at −10, 30-, 60-, 90-, 120-, and 180-min. Subjective appetite was determined with a visual analog scale. Food intake was measured at ad libitum buffet after 180 min. Results C-peptide iAUC was significantly higher for stevia (median (IQR): 1033 (711–1293) ng × min × L −1 ) vs. d -tagatose (794 (366–1134) ng × min × L −1 ; P = 0.001) or control (730 (516–1078) ng × min × L −1 ; P = 0.012). At 30- and 60-min serum glucose was higher for stevia vs other conditions ( P < 0.01). Volunteers reported greater satiety for stevia and d -tagatose vs. control at 60 min and greater desire to eat for stevia vs. control at 120- min (all P < 0.05). Objective appetite did not vary by condition ( P = 0.06). Conclusions Our findings suggest that these NNS are not inert. Stevia intake produced an acute response on C-peptide release while increased serum glucose at earlier times. It is possible that NNS affects subjective but not objective appetite. This trial is registered at clinicaltrials.gov as NCT04327245. Clinical trial registry NCT04327245.

Adenosine is an endogenous nucleoside with pleiotropic effects in different physiological processes including circulation, renal blood flow, immune function, or glucose homeostasis. Changes in adenosine membrane transporters, adenosine receptors, and corresponding intracellular signalling network associate with development of pathologies of pregnancy, including preeclampsia. Preeclampsia is a cause of maternal and perinatal morbidity and mortality affecting 3–5% of pregnancies. Since the proposed mechanisms of preeclampsia development include adenosine-dependent biological effects, adenosine membrane transporters and receptors, and the associated signalling mechanisms might play a role in the pathophysiology of preeclampsia. Preeclampsia associates with increased adenosine concentration in the maternal blood and placental tissue, likely due to local hypoxia and ischemia (although not directly demonstrated), microthrombosis, increased catecholamine release, and platelet activation. In addition, abnormal expression and function of equilibrative nucleoside transporters is described in foetoplacental tissues from preeclampsia; however, the role of adenosine receptors in the aetiology of this disease is not well understood. Adenosine receptors activation may be related to abnormal trophoblast invasion, angiogenesis, and ischemia/reperfusion mechanisms in the placenta from preeclampsia. These mechanisms may explain only a low fraction of the associated abnormal transformation of spiral arteries in preeclampsia, triggering cellular stress and inflammatory mediators release from the placenta to the maternal circulation. Although increased adenosine concentration in preeclampsia may be a compensatory or adaptive mechanism favouring placental angiogenesis, a poor angiogenic state is found in preeclampsia. Thus, preeclampsia-associated complications might affect the cell response to adenosine due to altered expression and activity of adenosine receptors, membrane transporters, or cell signalling mechanisms. This review summarizes the evidence available on the potential involvement of the adenosine in the clinical, pathophysiology, and therapeutic features of preeclampsia.

Adenosine as well as agonists and antagonists for the four adenosine receptor subtypes (A1R, A2AR, A2BR and A3R) play a role in several key physiological and pathophysiological processes, including the regulation of vascular tone , thrombosis, immune response, inflammation, and angiogenesis . This review focuses on the adenosine-mediated regulation of lipid availability in the cell and in the systemic circulation as well in humans and animal models . Therefore, adenosine, mainly by acting on A1R, inhibits lipolysis activity , leading to reduction of the circulating fatty acid levels . This nucleoside can also participate in the early development of atherosclerosis by inhibiting the formation of foam cells via stimulation of cholesterol efflux through A2AR expressed on macrophages and reduction of the inflammatory process by activating A2AR and A2BR. Adenosine also appears to modulate intracellular cholesterol availability in Niemann-Pick type C1 disease and Alzheimer disease via A2AR and A3, respectively. Remarkably, the role of adenosine receptors in the regulation of plasma total cholesterol and triglyceride levels has been studied in animal models. Thus, an anti-atherogenic role for A2BR as well as a pro-atherogenic role of A2AR and A1 have been proposed; A3R has not been shown to participate in the control of lipid levels or the development of atherosclerosis. Surprisingly, and despite the role of A2A in the inhibition of foam cell formation among isolated cells, this receptor appears to be pro-atherogenic in mice. Remarkably, the role of adenosine receptors in human dyslipidaemia and atherosclerosis must to be elucidated. Additionally, it has been reported that increased lipid levels impair the effects of adenosine/adenosine receptors in controlling vascular tone, and we speculate on the possibility that this impairment could be due to alterations in the composition of the membrane microdomains where the adenosine receptors are located. Finally, a possible role for adenosine/adenosine receptors in the phenomena of dyslipidaemia in pregnancy has been proposed.

Breast cancer (BC) clinical guidelines offer evidence-based recommendations to improve quality of healthcare for patients with or at risk of BC. Suboptimal adherence to recommendations has the potential to negatively affect population health. However, no study has systematically reviewed the impact of BC guideline adherence -as prognosis factor- on BC healthcare processes and health outcomes. The objectives are to analyse the impact of guideline adherence on health outcomes and on healthcare costs.

Estrogenic steroids and adenosine A2A receptors promote the wound healing and angiogenesis processes. However, so far, it is unclear whether estrogen may regulate the expression and pro-angiogenic activity of A2A receptors. Using in vivo analyses, we showed that female wild type (WT) mice have a more rapid wound healing process than female or male A2A-deficient mice (A2AKO) mice. We also found that pulmonary endothelial cells (mPEC) isolated from female WT mice showed higher expression of A2A receptor than mPEC from male WT mice. mPEC from female WT mice were more sensitive to A2A-mediated pro-angiogenic response, suggesting an ER and A2A crosstalk, which was confirmed using cells isolated from A2AKO. In those female cells, 17β-estradiol potentiated A2A-mediated cell proliferation, an effect that was inhibited by selective antagonists of estrogen receptors (ER), ERα, and ERβ. Therefore, estrogen regulates the expression and/or pro-angiogenic activity of A2A adenosine receptors, likely involving activation of ERα and ERβ receptors. Sexual dimorphism in wound healing observed in the A2AKO mice process reinforces the functional crosstalk between ER and A2A receptors.

Hace una década que la Educación Superior apostó por un cambio de modelo educativo y formativo, optando por implementar planes de estudios basados en la definición de competencias genéricas y específicas. Este artículo se centra en averiguar, desde una mirada interpretativa, cómo perciben docentes y estudiantes dicho cambio centrados en la evaluación por competencias, en los estudios relacionados con la docencia de la Educación Física para la Enseñanza Primaria y Secundaria. La información analizada se genera desde dos grupos de discusión: docentes y estudiantes, centrados en la evaluación por competencias. Las principales conclusiones las podemos resumir en falta de cultura de trabajo por competencias, lo que conlleva una evaluación que mantiene los viejos parámetros más centrados en calificar que en facilitar aprendizajes. En segundo lugar, se demanda, especialmente por parte del estudiantado, una formación más en contacto con la práctica real que permita un desarrollo de competencias real y efectivo.

Recognition memory comprises recollection judgment and familiarity, two different processes that engage the hippocampus and the perirhinal cortex, respectively. Previous studies have shown that aged rodents display defective recognition memory and alterations in hippocampal synaptic plasticity. We report here that young rats efficiently performed at short-term (5 min) and long-term (24 h) hippocampus-associated object-location tasks and perirhinal cortex-related novel-object recognition tasks. In contrast, aged rats successfully performed the object-location and the novel-object recognition tasks only at short-term. In addition, aged rats displayed defective long-term potentiation (LTP) and enhanced long-term depression (LTD). Successful long-term performance of object-location but not of novel-object recognition tasks increased the protein levels of ryanodine receptor types-2/3 (RyR2/RyR3) and of inositol 1,4,5-trisphosphate receptor type-1 (IP3R1) in young rat hippocampus. Likewise, sustained LTP induction (1 h) significantly increased RyR2, RyR3 and IP3R1 protein levels in hippocampal slices from young rats. In contrast, LTD induction (1 h) did not modify the levels of these three proteins. Naïve (untrained) aged rats displayed higher RyR2/RyR3 hippocampal protein levels but similar IP3R1 protein content relative to young rats; these levels did not change following exposure to either memory recognition task or after LTP or LTD induction. The perirhinal cortex from young or aged rats did not display changes in the protein contents of RyR2, RyR3 and IP3R1 after exposure at long-term (24 h) to the object-location or the novel-object recognition tasks. Naïve aged rats displayed higher RyR2 channel oxidation levels in the hippocampus compared to naïve young rats. The RyR2/RyR3 up-regulation and the increased RyR2 oxidation levels exhibited by aged rat hippocampus are likely to generate anomalous calcium signals, which may contribute to the well-known impairments in hippocampal LTP and spatial memory that take place during aging.

Objective To measure lung function by impulse oscillometry (IOS) and spirometry in recurrent wheezer pre-schoolers according to their asthma predictive index (API) condition. Methods We performed a case–control study enrolling all pre-schoolers with recurrent wheezing episodes (>3 episodes confirmed by physician) who presented at a paediatric pulmonology clinic. The population was divided according to stringent API criteria into positive or negative. Results In the nine-month period, 109 pre-schoolers were enrolled. After excluding one patient (due to lung function technique problems) 108 pre-schoolers (56 males, age range from 24 to 72 months) completed the study; 50 belong to positive API and 58 to negative API group. There were no differences in demographics between groups. More use of ICS was found in those with positive API than with negative API (62% vs. 12%, respectively, p = 0.001). No differences in basal lung function and post-bronchodilator response to salbutamol (by IOS or spirometry) were found between positive and negative API pre-schoolers. However, those positive API pre-schoolers with ICS had significantly higher central basal airway resistance (RA at 20 Hz) and higher post-BD response (% change in FEF 25–75 and in FEV 0.5 ) than those positive API without ICS. Conclusion Recurrent wheezer pre-schoolers with positive API and ICS used may have airway dysfunction. More studies are needed to confirm this finding.

Insulin resistance is characteristic of pregnancies where the mother shows metabolic alterations, such as preeclampsia (PE) and gestational diabetes mellitus (GDM), or abnormal maternal conditions such as pregestational maternal obesity (PGMO). Insulin signalling includes activation of insulin receptor substrates 1 and 2 (IRS1/2) as well as Src homology 2 domain-containing transforming protein 1, leading to activation of 44 and 42 kDa mitogen-activated protein kinases and protein kinase B/Akt (Akt) signalling cascades in the human foetoplacental vasculature. PE, GDM, and PGMO are abnormal conditions coursing with reduced insulin signalling, but the possibility of the involvement of similar cell signalling mechanisms is not addressed. This review aimed to determine whether reduced insulin signalling in PE, GDM, and PGMO shares a common mechanism in the human foetoplacental vasculature. Insulin resistance in these pathological conditions results from reduced Akt activation mainly due to inhibition of IRS1/2, likely due to the increased activity of the mammalian target of rapamycin (mTOR) resulting from lower activity of adenosine monophosphate kinase. Thus, a defective signalling via Akt/mTOR in response to insulin is a central and common mechanism of insulin resistance in these diseases of pregnancy. In this review, we summarise the cell signalling mechanisms behind the insulin resistance state in PE, GDM, and PGMO focused in the Akt/mTOR signalling pathway in the human foetoplacental endothelium.

Alternative lengthening of telomeres (ALT) is a telomere maintenance mechanism activated in ~10–15% of cancers, characterized by telomeric damage. Telomeric damage-induced long non-coding RNAs (dilncRNAs) are transcribed at dysfunctional telomeres and contribute to telomeric DNA damage response (DDR) activation and repair. Here we observed that telomeric dilncRNAs are preferentially elevated in ALT cells. Inhibition of C-rich (teloC) dilncRNAs with antisense oligonucleotides leads to DNA replication stress responses, increased genomic instability, and apoptosis induction selectively in ALT cells. Cell death is dependent on DNA replication and is increased by DNA replication stress. Mechanistically, teloC dilncRNA inhibition reduces RAD51 and 53BP1 recruitment to telomeres, boosts the engagement of BIR machinery, and increases C-circles and telomeric sister chromatid exchanges, without increasing telomeric non-S phase synthesis. These results indicate that teloC dilncRNA is necessary for a coordinated recruitment of DDR factors to ALT telomeres and it is essential for ALT cancer cells survival. Similar content being viewed by others