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We analyze the vacuum structure of the one-loop effective potential in thetwo Higgs doublet model. We find that electroweak-breaking vacuua can coexistwith charge breaking ones, contradicting a theorem valid at tree-level. Weperform a numerical analysis of the model and supply explicit parameter valuesfor which charge-breaking vacuua can be the global minimum of the theory, anddeeper than charge-preserving ones.

Competing Interests: The authors have no funding or conflicts of interest to disclose.

Background: Obstructive sleep apnea (OSA), due to its high prevalence, has been associated with a number of comorbidities, frequently impacting the overall course of these other diseases if left untreated. Recent studies highlight a potential association between OSA and cancer. This study investigates how OSA severity and hypoxia affect cancer prognosis, aiming to elucidate how they interplay., Methods: Retrospective study including patients with a diagnosis of OSA after any cancer type followed up in a tertiary center during a 10-year period. OSA was mainly diagnosed after level III polysomnographic studies., Results: Nocturnal hypoxia was significantly more prevalent in patients presenting lung cancer versus other malignancies and was associated with higher rates of oncologic disease progression. Overall survival was significantly lower in severe OSA patients and also in patients presenting nocturnal hypoxia. A composite hypoxia score considering both OSA severity and significant hypoxia was an independent predictor of mortality regardless of clinical cancer staging and treatment. Shorter time between cancer and OSA diagnosis was also associated with worse prognosis., Conclusion: This study suggests an association between OSA severity and nocturnal hypoxia and increased cancer mortality independently from possible confounding factors such as age, cancer clinical staging at diagnosis, treatment modality and also progression. Neoplastic patients with severe OSA and/or complex hypoxia seem to have lower overall survival rates than those with less severe OSA and nocturnal hypoxia., Competing Interests: Declaration of competing interest I hereby declare that the disclosed information is correct and that no other situation of real, potential, or apparent conflict of interest is known to me. I undertake to inform you of any change in these circumstances, including if an issue arises during the course of the meeting or work itself., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Cercarial dermatitis (CD), or "Swimmer's itch" as it is also known, is a waterborne illness caused by a blood fluke from the family Schistosomatidae. It occurs when cercariae of trematode species that do not have humans as their definitive host accidentally penetrate human skin (in an aquatic environment) and trigger allergic symptoms at the site of contact. It is an emerging zoonosis that occurs through water and is often overlooked during differential diagnosis. Some of the factors contributing to the emergence of diseases like CD are related to global warming, which brings about climate change, water eutrophication, the colonization of ponds by snails susceptible to the parasite, and sunlight exposure in the summer, associated with migratory bird routes. Therefore, with the increase in tourism, especially at fluvial beaches, it is relevant to analyze the current epidemiological scenario of CD in European countries and the potential regions at risk.

Frequent droughts have led to an expansion of irrigated common bean (Phaseolus vulgaris L.) cultivation areas. An effective strategy to enhance water use efficiency and optimize crop growth is the application of silicon (Si) and potassium (K). However, the interaction between Si dosage, water regimes, and plant potassium status, as well as the underlying physiological mechanisms, remains unknown. This study aimed to assess the effects of Si doses applied via fertigation under various water regimes, in the presence and absence of potassium fertilization, on gas exchange, water use efficiency, and growth of Common beans in field conditions. Two experiments were conducted, one with and one without K supply, considering that the potassium content in the soil was 6.4 mmol c dm -3 in both experiments and a replacement dose of 50 kg ha was applied in the with K treatment, with the same treatments evaluated in both potassium conditions. The treatments comprised a 3 × 4 factorial design, encompassing three water regimes: 80% (no deficit), 60% (moderate water deficit), and 40% (severe water deficit) of soil water retention capacity, and four doses of Si supplied via fertigation: 0, 4, 8, and 12 kg ha -1 . Where it was evaluated, content of photosynthetic pigments, fluorescence of photosynthesis, relative water content, leaf water potential and electrolyte extravasation, dry mass of leaves, stems and total. The optimal doses of Si for fertigation application, leading to increased Si absorption in plants, varied with decreasing soil water content. The respective values were 6.6, 7.0, and 7.1 kg ha -1 for the water regimes without deficit, with moderate water deficit, and with severe water deficit. Fertigation application of Si improved plant performance, particularly under severe water deficit, regardless of potassium status. This improvement was evident in relative water content, leaf water potential, and membrane resistance, directly impacting pigment content and gas exchange rates. The physiological effects resulted in enhanced photosynthesis in water-deficient plants, mitigating dry mass production losses. This research demonstrates, for the first time in common bean, the potential of Si to enhance irrigation efficiency in areas limited by low precipitation and water scarcity., (© 2024. The Author(s).)

Background: The benefits of physical activity (PA) and adequate sleep are well documented, and their importance strengthens with the increasing prevalence of chronic diseases and multimorbidity (MM). Interventions to promote physical activity and sleep that use commercial activity trackers may be useful non-pharmacological approaches to managing individual health; however, limited evidence exists on their use to improve physical activity in older adult patients with MM., Methods: This study aims to measure the effects of behavioral change techniques (BCTs) delivered by a wearable device on physical activity and quality of sleep (QS) in older adult patients with MM. We designed an open-label randomized controlled trial with participants recruited through primary care and a specialist outpatient clinic. Participants must be more than 65 years old, have MM, and have access to smartphones. All eligible participants will receive PA promotion content and will be randomly assigned to wear a smartwatch. The primary outcome will be the participants' PA measurement at baseline and at six months using the International Physical Activity Questionnaire - Short Form (IPAQ-SF). Secondary outcomes will include changes in the participants' frailty status, biometric measurements, quality of life, and biopsychosocial assessments. A sample size of 40 participants per arm was calculated to detect group differences, with 50 participants planned to recruit and randomize into each arm., Discussion: This study aims to contribute to a better understanding of PA patterns and the impact of wearable-based PA interventions in patients with MM. In addition, we aim to contribute to more knowledge about the relationship between PA patterns, Patient Reported Outcomes Measures (PROMs), and healthcare resource utilization in patients with MM. To achieve this, the study will leverage a locally developed PROMs registry and assess data from participants' medical records, in order to understand the added impact of wearable data and medical information data on predicting PROMs and unplanned hospital admissions., Trial Registration: NCT05777291., (© 2023. The Author(s).)

Droplet manipulation has garnered significant attention in various fields due to its wide range of applications. Among many different methods, magnetic actuation has emerged as a promising approach for remote and instantaneous droplet manipulation. In this study, we present the bidirectional droplet manipulation on a magnetically actuated superhydrophobic ratchet surface. The surface consists of silicon strips anchored on elastomer ridges with superhydrophobic black silicon structures on the top side and magnetic layers on the bottom side. The soft magnetic properties of the strips enable their bidirectional tilting to form a ratchet surface and thus bidirectional droplet manipulation upon varying external magnetic field location and strength. Computational multiphysics models were developed to predict the tilting of the strips, demonstrating the concept of bidirectional tilting along with a tilting angle hysteresis theory. Experimental results confirmed the soft magnetic hysteresis and consequential bidirectional tilting of the strips. The superhydrophobic ratchet surface formed by the tilting strips induced the bidirectional self-propulsion of dispensed droplets through the Laplace pressure gradient, and the horizontal acceleration of the droplets was found to be positively correlated with the tilting angle of the strips. Additionally, a finite element analysis was conducted to identify the critical conditions for dispensed droplet penetration through the gaps between the strips, which hinder the droplet's self-propulsion. The models and findings here provide substantial insights into the design and optimization of magnetically actuated superhydrophobic ratchet surfaces to manipulate droplets in the context of digital microfluidic applications.

Background: Demographic changes in the world population have resulted in an increasingly aging society, with a progressive increase in the number of people in situations of dependence, who require assistance from family members to meet their basic needs. Caring for older adults involves performing diverse activities, resulting in reduced free time and tiredness, and fulfilling the demands and expectations related to personal, family, physical, and social life, consequently compromising the quality of life of the caregiver. In this context, the informal caregiver of hospitalized older adults emerges as the focus of attention., Objective: The aim of this study was to describe the sociodemographic profile, health conditions, and burden of informal caregivers of older adults admitted to a university hospital in Brazil during the COVID-19 pandemic period., Methods: This is a cross-sectional, descriptive, and analytical study that was conducted with 25 informal caregivers of hospitalized older adults in a university hospital in Brazil between August and September 2022. Three instruments were applied: Caregiver Burden Inventory, sociodemographic questionnaire, and health conditions questionnaire. The data were analyzed using SPSS version 28.0. Descriptive (frequency and percentage) and inferential analyses were performed using 2-sided Student t test with 95% CIs., Results: Of the 25 interviewees, 18 (72%) were females, 17 (46%) were married or in a stable union, 14 (56%) completed secondary education, and 11 (44%) lived with the older adults who needed care. The average age of the participants was 44 (SD 12.8) years. Regarding their health conditions, most caregivers self-reported it as good (12/25, 48%). They provided care to their father or mother older than 70 years (14/25, 56%). The Caregiver Burden Inventory analysis showed that the caregivers were the most negatively impacted in the domains of personal life overload (mean 10.8, SD 3.46; P=.047) and physical overload (mean 10.6, SD 2.32; P=.02)., Conclusions: In recent years, there has been an increase in the burden on informal caregivers of hospitalized older adults in Brazil, thereby impacting their personal and physical lives. The findings of our study show that health care professionals should be trained to promote health guidelines and actions to improve the personal and physical lives of the caregiver population in Brazil., (©Pâmela Moraes Ferreira, Mateus Cunha Gomes, Lucianne Nascimento de Araujo, Tainá Sayuri Onuma de Oliveira, Glenda Ferreira, Cintia Aben-Athar, Silvio Eder Dias da Silva, Aline M P Cruz Ramos, Diego Pereira Rodrigues, Fabianne Sousa. Originally published in JMIR Formative Research (https://formative.jmir.org), 23.11.2023.)

Intensive fertilization of vegetables can promote phosphorus (P) toxicity. However, it can be reversed using silicon (Si), although there is a lack of research clarifying its mechanisms of action. This research aims to study the damage caused by P toxicity to scarlet eggplant plants and whether Si can mitigate this toxicity. We evaluated the nutritional and physiological aspects of plants. Treatments were arranged in a 2 × 2 factorial design of two nutritional levels of adequate P (2 mmol L -1 of P) and toxic/excess P (8 to 13 mmol L -1 of P) combined with the absence or presence of nanosilica (2 mmol L -1 Si) in a nutrient solution. There were six replications. The excess P in the nutrient solution caused damage to scarlet eggplant growth due to nutritional losses and oxidative stress. We found that P toxicity can be mitigated by supplying Si, which decreases P uptake by 13%, improves C:N homeostasis, and increases iron (Fe), copper (Cu), and zinc (Zn) use efficiency by 21%, 10%, and 12%, respectively. At the same time, it decreases oxidative stress and electrolyte leakage by 18% and increases antioxidant compounds (phenols and ascorbic acid by 13% and 50%, respectively), and decreases photosynthetic efficiency and plant growth by 12% (by increasing 23% and 25% of shoot and root dry mass, respectively). These findings allow us to explain the different Si mechanisms used to reverse the damage caused by P toxicity to plants., (© 2023. The Author(s).)

Background: Due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, recently, Radiotherapy (RT) protocols requiring fewer sessions (hypofractionated) have been used to shorten RT treatment and minimize patient exposure to medical centers, and decrease the risk of SARS-CoV-2 infection., Methods: This longitudinal, prospective, observational study aimed to compare the quality of life (QoL) and the incidence of oral mucositis and candidiasis in 66 patients with head and neck cancer (HNC) who undergo a hypofractionated RT protocol (GHipo), total of 55 Gy for 4 weeks, or a conventional RT protocol (GConv), total of 66 - 70 Gy for 6 - 7 weeks., Purpose: To assess the incidence and severity of oral mucositis, the incidence of candidiasis, and QoL were evaluated using the World Health Organization scale, clinical evaluation, and the QLC-30 and H&N-35 questionnaires, respectively, at the beginning and the end of RT., Results: The incidence of candidiasis did not show differences between the two groups. However, at the end of RT, mucositis had a higher incidence (p < 0.01) and severity (p < 0.05) in GHipo. QoL was not markedly different between the two groups. Although mucositis worsened in patients treated with hypofractionated RT, QoL did not worsen for patients on this regimen., Conclusions: Our results open perspectives for the potential use of RT protocols for HNC with fewer sessions in conditions that require faster, cheaper, and more practical treatments., (© 2023. The Author(s).)

Brazil experienced one of the fastest increasing numbers of coronavirus disease (COVID-19) cases worldwide. The Sao Paulo State (SPS) reported a high incidence, particularly in Sao Paulo municipality. This study aimed to identify clusters of incidence and mortality of hospitalized patients with severe acute respiratory syndrome for COVID-19 in the SPS, in 2020-2021, and describe the origin flow pattern of the cases. Cases and mortality risk area clusters were identified through different analyses (spatial clusters, spatio-temporal clusters, and spatial variation in temporal trends) by weighting areas. Ripley's K12-function verified the spatial dependence between the cases and infrastructure. There were 517,935 reported cases, with 152,128 cases resulting in death. Of the 470,441 patients hospitalized and residing in the SPS, 357,526 remained in the original municipality, while 112,915 did not. Cases and death clusters were identified in the Sao Paulo metropolitan region (SPMR) and Baixada Santista region in the first study period, and in the SPMR and the Campinas, Sao Jose do Rio Preto, Barretos, and Sorocaba municipalities during the second period. We highlight the priority areas for control and surveillance actions for COVID-19, which could lead to better outcomes in future outbreaks.

Every year, the VISion Understanding and Machine intelligence (VISUM) summer school runs a competition where participants can learn and share knowledge about Computer Vision and Machine Learning in a vibrant environment. 2021 VISUM's focused on applying those methodologies in fashion. Recently, there has been an increase of interest within the scientific community in applying computer vision methodologies to the fashion domain. That is highly motivated by fashion being one of the world's largest industries presenting a rapid development in e-commerce mainly since the COVID-19 pandemic. Computer Vision for Fashion enables a wide range of innovations, from personalized recommendations to outfit matching. The competition enabled students to apply the knowledge acquired in the summer school to a real-world problem. The ambition was to foster research and development in fashion outfit complementary product retrieval by leveraging vast visual and textual data with domain knowledge. For this, a new fashion outfit dataset (acquired and curated by FARFETCH) for research and benchmark purposes is introduced. Additionally, a competitive baseline with an original negative sampling process for triplet mining was implemented and served as a starting point for participants. The top 3 performing methods are described in this paper since they constitute the reference state-of-the-art for this particular problem. To our knowledge, this is the first challenge in fashion outfit complementary product retrieval. Moreover, this joint project between academia and industry brings several relevant contributions to disseminating science and technology, promoting economic and social development, and helping to connect early-career researchers to real-world industry challenges., (© The Author(s) 2022.)

Beans reached the research spotlight as a source of bioactive compounds capable of modulating different functions. Recently, we reported antioxidant and oxidonitrergic effect of a low molecular weight peptide fraction (<3 kDa) from hardened bean ( Phaseolus vulgaris ) in vitro and ex vivo , which necessitate further in vivo assessments. This work aimed to evaluate the hypotensive effect and the involved physiological mechanisms of the hardened common bean peptide (Phaseolus vulgaris ) in normotensive (Wistar) and hypertensive (SHR) animals. Bean flour was combined with a solution containing acetonitrile, water and formic acid (25: 24: 1). Protein extract (PV3) was fractioned (3 kDa membrane). We assessed PV3 effects on renal function and hemodynamics of wistar (WT-normotensive) and spontaneously hypertensive rats (SHR) and measured systemic arterial pressure and flow in aortic and renal beds. The potential endothelial and oxidonitrergic involvements were tested in isolated renal artery rings. As results, we found that PV3: I) decreased food consumption in SHR, increased water intake and urinary volume in WT, increased glomerular filtration rate in WT and SHR, caused natriuresis in SHR; II) caused NO- and endothelium-dependent vasorelaxation in renal artery rings; III) reduced arterial pressure and resistance in aortic and renal vascular beds; IV) caused antihypertensive effects in a dose-dependent manner. Current findings support PV3 as a source of bioactive peptides and raise the potential of composing nutraceutical formulations to treat renal and cardiovascular diseases., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

This research aimed to study the effects of the nanosilica supply on Si absorption and the physiological and nutritional aspects of beet plants with N and P deficiencies cultivated in a nutrient solution. Two experiments were performed with treatments arranged in a 2 × 2 factorial scheme in randomized blocks with five replications. The first experiment was carried out on plants under a N deficiency and complete (complete solution with all nutrients), combined with the absence of Si (0 mmol L -1 ) and the presence of Si (2.0 mmol L -1 ). In the other experiment, the plants were cultivated in a nutrient solution with a P deficiency and complete, combined with the absence (0 mmol L -1 ) and the presence of Si (2.0 mmol L -1 ). The beet crop was sensitive to the N and P deficiencies because they sustained important physiological damage. However, using nanosilica via fertigation could reverse the damage. Using nanotechnology from nanosilica constituted a sustainable strategy to mitigate the damage due to a deficiency in the beet crop of the two most limiting nutrients by optimizing the physiological processes, nutritional efficiency, and growth of the plants without environmental risks. The future perspective is the feasibility of nanotechnology for food security.

Sensing Technology (ST) plays a key role in Structural Health-Monitoring (SHM) systems. ST focuses on developing sensors, sensory systems, or smart materials that monitor a wide variety of materials' properties aiming to create smart structures and smart materials, using Embedded Sensors (ESs), and enabling continuous and permanent measurements of their structural integrity. The integration of ESs is limited to the processing technology used to embed the sensor due to its high-temperature sensitivity and the possibility of damage during its insertion into the structure. In addition, the technological process selection is dependent on the base material's composition, which comprises either metallic or composite parts. The selection of smart sensors or the technology underlying them is fundamental to the monitoring mode. This paper presents a critical review of the fundaments and applications of sensing technologies for SHM systems employing ESs, focusing on their actual developments and innovation, as well as analysing the challenges that these technologies present, in order to build a path that allows for a connected world through distributed measurement systems.

Background: Medical students have a considerable prevalence of anxiety and substance use disorders. Our aim was to assess the presence of anxiety disorders and the use of alcohol and licit and illicit substances, and their influence on the academic performance of medical students., Methods: This is a cross-sectional, non-experimental pilot study, with quantitative analyses, in which 67 medical students at the Federal University of Rondonópolis, Mato Grosso, Brazil (UFR), were evaluated through the application of non-invasive anxiety assessment instruments, screening for involvement with tobacco, alcohol and other substances, related to school performance coefficient, between June 2019 and March 2020., Results: Worse academic performance was associated with frequent use of tobacco and its derivatives (p = 0.0022), marijuana (p = 0.0020), hypnotics and sedatives (p = 0.0138). Also, the performance was negatively correlated with the use of tobacco (p = 0.0004), alcoholic beverages (p = 0.0261), cannabis (p = 0.0075), sedatives (p = 0.0116) and trait anxiety (p = 0.0036). Greater trait anxiety intensity was associated with previous use of tobacco (p = 0.0276), marijuana (p = 0.0466), amphetamines/ecstasy (p = 0.0151), and hypnotics/sedatives (p = 0.0103). State anxiety was positively correlated with heavy alcohol use (p = 0.0434). Higher state anxiety intensity was related to needing intervention due to the use of amphetamines/ecstasy (p = 0.00379). Students from the intermediate classes of the course (3rd and 4th years) had a higher frequency and intensity of use of tobacco and its derivatives (p = 0.0133), amphetamines or ecstasy (p = 0.0006), and inhalants (p = 0.0256)., Conclusions: Worse academic performance in medical students was correlated with licit and illicit substances use and anxiety disorders. Mid-course students had a higher frequency and intensity of substance use., (© 2022. The Author(s).)

Studies describing characteristics and outcomes of COVID-19 among people living with HIV are currently limited, lacking detailed evaluation of the interplay among demographics, HIV-related variables, and comorbidities on COVID-19 outcomes. This retrospective cohort study describes mortality rates overall and according to demographic characteristics and explores predictors of admission to intensive care unit and death among 255 persons living with HIV with severe acute respiratory syndrome and confirmed SARS-CoV-2 infection in the State of Sao Paulo, Brazil. We found that the overall mortality rate was 4.1/1,000 person-days, with a case-fatality of 34%. Higher rates occurred among older adults, Black/Mixed skin color/race patients, and those with lower schooling. In a multivariable analysis adjusted for age, sex, CD4 count, viral load and number of comorbidities, skin color/race, and schooling remained significantly associated with higher mortality. Although tenofovir use was more frequent among survivors in the univariable analysis, we failed to find a statistically significant association between tenofovir use and survival in the multivariable analysis. Our findings suggest that social vulnerabilities related to both HIV and COVID-19 significantly impact the risk of death, overtaking traditional risk factors such as age, sex, CD4 count, and comorbidities.

To overcome the multifactorial complexity associated with the analysis and interpretation of the capillary electrophoresis results of forensic mixture samples, probabilistic genotyping methods have been developed and implemented as software, based on either qualitative or quantitative models. The former considers the electropherograms' qualitative information (detected alleles), whilst the latter also takes into account the associated quantitative information (height of allele peaks). Both models then quantify the genetic evidence through the computation of a likelihood ratio (LR), comparing the probabilities of the observations given two alternative and mutually exclusive hypotheses. In this study, the results obtained through the qualitative software LRmix Studio (v.2.1.3), and the quantitative ones: STRmix™ (v.2.7) and EuroForMix (v.3.4.0), were compared considering real casework samples. A set of 156 irreversibly anonymized sample pairs (GeneMapper files), obtained under the scope of former cases of the Portuguese Scientific Police Laboratory, Judiciary Police (LPC-PJ), were independently analyzed using each software. Sample pairs were composed by (i) a mixture profile with either two or three estimated contributors, and (ii) a single contributor profile associated. In most cases, information on 21 short tandem repeat (STR) autosomal markers were considered, and the majority of the single-source samples could not be a priori excluded as belonging to a contributor to the paired mixture sample. This inter-software analysis shows the differences between the probative values obtained through different qualitative and quantitative tools, for the same input samples. LR values computed in this work by quantitative tools showed to be generally higher than those obtained by the qualitative. Although the differences between the LR values computed by both quantitative software showed to be much smaller, STRmix™ generated LRs are generally higher than those from EuroForMix. As expected, mixtures with three estimated contributors showed generally lower LR values than those obtained for mixtures with two estimated contributors. Different software products are based on different approaches and mathematical or statistical models, which necessarily result in the computation of different LR values. The understanding by the forensic experts of the models and their differences among available software is therefore crucial. The better the expert understands the methodology, the better he/she will be able to support and/or explain the results in court or any other area of scrutiny., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: The evolving COVID-19 pandemic became a hallmark in human history, not only by changing lifestyles, but also by enriching scientific knowledge on viral infection and its consequences., Objective: Although the management of cardiorespiratory changes is pivotal to a favorable prognosis during severe clinical findings, dysregulation of other systems caused by SARS-CoV-2 infection may imbalance erythrocyte dynamics, such as a bidirectional positive feedback loop pathophysiology., Method and Results: Recent evidence shows that SARS-CoV-2 is capable of affecting the genetics and dynamics of erythrocytes and this coexists with a non-homeostatic function of cardiovascular, respiratory and renal systems during COVID-19. In hypothesis, SARS-CoV-2-induced systematical alterations of erythrocytes dynamics would constitute a setpoint for COVID-19-related multiple organ failure syndrome and death., Conclusion: The present review covers the most frequent erythrocyte-related non-homeostatic findings during COVID-19 capable of providing mechanistic clues of SARS-CoV-2-induced infection and inspiring therapeutic-oriented scientific evidence., Competing Interests: The authors declare no conflicts of interest., (© 2022 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier España, S.L.U.)

Fire is a frequent disturbance in most grasslands around the world, being key for the structure and dynamics of the biodiversity in such ecosystems. While grassland species may be resilient, little is known on how plant-pollinator networks reassemble after fire. Here, we investigate the structure and dynamics of plant-pollinator networks and the variation in species roles over a 2-year post-fire chronosequence on grassland communities in Southern Brazil. We found that both network specialization and modularity were similar over the chronosequence of time-since-fire, but in freshly burnt areas, there were more species acting as network hubs. Species roles exhibited high variation, with plant and pollinator species shifting roles along the post-disturbance chronosequence. Interaction dissimilarity was remarkably high in networks irrespective of times-since-fire. Interaction dissimilarity was associated more with rewiring than with species turnover, indicating that grassland plant and pollinator species are highly capable of switching partners. Time-since-fire had little influence on network structure but influenced the identity and diversity of pollinators playing key roles in the networks. These findings suggest that pollination networks in naturally fire-prone ecosystems are highly dynamic and resilient to fire with both plants and pollinators being highly capable of adjusting their interactions and network structure after disturbance., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Mimosa caesalpiniifolia (Fabaceae) is used by Brazilian people to treat hypertension, bronchitis, and skin infections. Herein, we evaluated the antiproliferative action of the dichloromethane fraction from M. caesalpiniifolia (DFMC) stem bark on murine tumor cells and the in vivo toxicogenetic profile. Initially, the cytotoxic activity of DFMC on primary cultures of Sarcoma 180 (S180) cells by Alamar Blue, trypan, and cytokinesis block micronucleus (CBMN) assays was assessed after 72 h of exposure, followed by the treatment of S180-bearing Swiss mice for 7 days, physiological investigations, and DNA/chromosomal damage. DFMC and betulinic acid revealed similar in vitro antiproliferative action on S180 cells and induced a reduction in viable cells, induced a reduction in viable cells and caused the emergence of bridges, buds, and morphological features of apoptosis and necrosis. S180-transplanted mice treated with DFMC (50 and 100 mg/kg/day), a betulinic acid-rich dichloromethane, showed for the first time in vivo tumor growth reduction (64.8 and 80.0%) and poorer peri- and intratumor quantities of vessels. Such antiproliferative action was associated with detectible side effects (loss of weight, reduction of spleen, lymphocytopenia, and neutrophilia and increasing of GOT and micronucleus in bone marrow), but preclinical general anticancer properties of the DFMC were not threatened by toxicological effects, and these biomedical discoveries validate the ethnopharmacological reputation of Mimosa species as emerging phytotherapy sources of lead molecules., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2021 Paulo Michel Pinheiro Ferreira et al.)

Coronavirus Disease 2019 pandemic remains a threat to public health. We report 2 cases of Coronavirus Disease 2019 infection in the same healthcare professional in Brazil. Genomic analysis identified that primoinfection was caused by the endemic lineage B.1.1.33 while reinfection by the lineage B.1.1.44, a lineage with an additional V1176F mutation in S protein., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Toxocariasis is one of the most widespread and important zoonotic parasitic diseases, although neglected. Data regarding human Toxocara infection in Portugal are almost absent. This article gives an overview of the situation of toxocariasis in Portugal over the last decade based on casuistic data. A total of 846 serum samples from individuals suspected of toxocariasis, collected from 2010 to 2020, were analyzed at the Institute of Hygiene and Tropical Medicine. Sera were tested for IgG antibodies to Toxocara canis excreted-secreted larval antigens by enzyme-linked immunosorbent assay and counterimmunoelectrophoresis. Positivity was detected in 18.8% (159/846) [CI 95%: 16.3-21.6], with positives detected throughout continental Portugal. Overall, 59.7% of the positives were diagnosed in younger than 20 years (35.2% aged 0-9 years and 24.5% aged 10-19 years). Eosinophilia was the most frequent feature reported (27.7%). Pediatrics (41.5%) and Infectiology (25.8%) were the specialties with the highest number of positives. An average of 77 samples/year were received, recording a maximum positivity in 2012 (41.5%, n = 27/65) and a minimum in 2020 (6.4%, n = 3/47). These numbers may reflect the effectiveness of current preventive measures, highlighting the need to maintain public awareness to control this helminthozoonosis and promote a higher public health standard.

In this paper, a Multi-Objective Genetic Algorithm (MOGA) framework for the design of Artificial Neural Network (ANN) models is used to design 1-step-ahead prediction models of river water levels. The design procedure is a near-automatic method that, given the data at hand, can partition it into datasets and is able to determine a near-optimal model with the right topology and inputs, offering a good performance on unseen data, i.e., data not used for model design. An example using more than 11 years of water level data (593,178 samples) of the Carrión river collected at Villoldo gauge station shows that the MOGA framework can obtain low-complex models with excellent performance on unseen data, achieving an RMSE of 2.5 × 10 -3 , which compares favorably with results obtained by alternative design.

Objectives: To retrospectively describe severe cases of hospitalized patients and deaths related to the COVID-19 epidemic in the state of São Paulo, starting from the date of the first record, with symptoms onset on 02/10/2020 up to 05/20/2021., Methods: This is a descriptive study carried out using the Influenza Epidemiological Surveillance System (Sistema de Vigilância Epidemiológica da Gripe - SIVEP-Gripe) database. The rates of incidence, mortality, and accumulated incidence in the period were calculated, stratified by age group and Regional Health Department (RHD). In addition, severe cases were geocoded to analyze their spread across the state; and the Effective R, which determines the spread potential of a virus within a population, was calculated., Results: There was a significant increase in severe cases and deaths recorded in the period of one year, with incidence and mortality rates being heterogeneous within the state. The most critical periods regarding the incidence of severe cases occurred between May and July 2020 and between March and April 2021. The RHD in São José do Rio Preto, Expanded São Paulo, and Araçatuba concentrated the highest incidence and mortality rates. Severe cases and deaths were more frequent in men and in the population over 60 years, while the main risk conditions related to deaths were heart disease (59%) and diabetes (42,8%)., Conclusions: These results not only provide a detailed profile for more efficient control action plan, but will also allow the historical understanding of the COVID-19 evolution within the state of São Paulo.

Arsenopyrite (FeAsS), the most common arsenic-bearing mineral, is usually found associated with pyrite (FeS 2 ) in gold mining tailings. This work examined the galvanic effect of FeS 2 on As release from FeAsS oxidation in circumneutral media under oxygen-depleted and oxygen-saturated conditions. The oxidation experiments were conducted with a flow-through reactor in the absence of FeS 2 particles and in the presence of different contents of this sulfide. The results indicated that the permanent, physical contact between FeAsS and FeS 2 particles causes an increase in the accumulated As release, mainly under O 2 -saturated conditions. At 30% wt. FeS 2 , the increases relatively to FeS 2 -free conditions were 82% and 117% in O 2 -depleted and O 2 -saturated solutions, respectively. At steady-state, the As release rates increased from (4.9 ± 0.5)× 10 -4 µmol m -2 s -1 (0% wt. FeS 2 ) to (1.1-1.9)× 10 -3 µmol m -2 s -1 (5-30% wt. FeS 2 ) under O 2 -saturated conditions. Analysis of FeAsS samples after oxidation revealed oxidized particles partially or entirely covered by precipitates with different sizes, shapes and compositions (e.g., As-S-bearing ferrihydrite, elemental sulfur, and As-O phases). A fine (3-4 nm thick) amorphous layer of S-As-bearing ferric oxy-hydroxide was also identified on oxidized FeAsS, with Fe(III) and As(III) species., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Platelets release platelet-derived extracellular vesicles (PDEVs) upon activation - in a process that is regulated by generation of reactive oxygen species (ROS). Platelet NADPH oxidase-1 (Nox-1) contributes to ROS generation and thrombus formation downstream of the collagen receptor GPVI., Objectives: We aimed to investigate whether PDEVs contain Nox-1 and whether this is relevant for PDEV-induced platelet activation., Methods: PDEVs were isolated through serial centrifugation after platelet activation with thrombin receptor agonist TRAP-6 (activated PDEVs) or in the absence of agonist (resting PDEVs). The physical properties of PDEVs were analyzed through nanoparticle tracking analysis. Nox-1 levels, fibrinogen binding and P-selectin exposure were measured using flow cytometry, and protein levels quantified by immunoblot analysis. ROS were quantified using DCF fluorescence and electron paramagnetic resonance., Results: Nox-1 was found to be increased on the platelet outer membrane upon activation and was present in PDEVs. PDEVs induced platelet activation, while co-addition of GPVI agonist collagen-related peptide (CRP) did not potentiate this response. PDEVs were shown to be able to generate superoxide in a process at least partially mediated by Nox-1, while Nox-1 inhibition with ML171 (also known as 2-APT) did not influence PDEV production. Finally, inhibition of Nox-1 abrogated PDEV-mediated platelet activation., Conclusions: PDEVs are able to generate superoxide, bind to and activate platelets in a process mediated by Nox-1. These data provide novel mechanisms by which Nox-1 potentiates platelet responses, thus proposing Nox-1 inhibition as a feasible strategy to treat and prevent thrombotic diseases., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aims: To test the hypothesis that, in comparison with control, experimental noxious stimulation of the right masseter muscle would result in significant changes in the firing rates, thresholds, and recruitment orders of single-motor units (SMUs) of the nonpainful, synergistic right anterior temporalis muscle during goal-directed isometric biting task performance., Methods: Twenty healthy volunteers received an infusion of hypertonic saline (HS; 5% sodium chloride) into the right masseter to produce pain intensity of 40 to 60 on a 100-mm visual analog scale (VAS). Isotonic saline (IS) infusion was a control. Standardized biting tasks were performed with an intraoral force transducer, and intramuscular electromyographic activity was recorded from the right anterior temporalis muscle. Tasks (slow and fast ramp biting tasks, two-step biting task) were performed in 3 blocks: baseline, HS infusion, and IS infusion. Across blocks, SMU thresholds and firing rates were statistically compared, and SMU recruitment sequences were qualitatively compared. Statistical significance was set at P < .05., Results: No significant differences (P > .05) were noted between HS and IS infusion blocks in thresholds or firing rates of anterior temporalis SMUs. Individual SMUs showed increases or decreases in thresholds or firing rates or changes in recruitment sequences mostly during HS compared to IS infusion., Conclusion: The reorganization of SMU activity that has been suggested to occur in both painful and nonpainful agonist jaw muscles may involve not only recruitments and de-recruitments of SMUs, but may also extend to more subtle increases and/or decreases in firing rates, thresholds, and recruitment sequences of individual SMUs in the nonpainful synergistic muscles.

Background: Acute Kidney Injury (AKI), a common disease of the urinary system, can be induced by high doses of gentamicin (GM). The renin-angiotensin system exerts a key role in the progression of the AKI since elevated intrarenal levels of Ang II, and ACE activity is found in this condition. However, it is unknown whether oral administration of angiotensin (Ang)-(1-7), a heptapeptide that evokes opposite effects of Ang II, may attenuate the renal injuries induced by gentamicin., Objectives: To evaluate the effects of Ang-(1-7) on GM-induced renal dysfunction in rats., Methods: AKI was induced by subcutaneous administration of GM (80 mg/Kg) for 5 days. Simultaneously, Ang-(1-7) included in hydroxypropyl β-cyclodextrin (HPβCD) was administered by gavage [46 μg/kg HPβCD + 30 μg/kg Ang-(1-7)]. At the end of the treatment period (sixth day), the rats were housed in metabolic cages for renal function evaluation. Thereafter, blood and kidney samples were collected., Results: Ang-(1-7) attenuated the increase of the plasmatic creatinine and proteinuria caused by GM but did not change the glomerular filtration rate nor tubular necrosis. Ang-(1-7) attenuated the increased urinary flow and the fractional excretion of H2O and potassium observed in GM rats but intensified the elevated excretion of sodium in these animals. Morphological analysis showed that Ang-(1-7) also reduced the tubular vacuolization in kidneys from GM rats., Conclusion: Ang-(1-7) promotes selective beneficial effects in renal injuries induced by GM., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Ghrelin is a peptide hormone whose effects are mediated by the growth hormone secretagogue receptor subtype 1a (GHS-R1a), mainly expressed in the brain but also in kidneys. The hypothesis herein raised is that GHS-R1a would be player in the renal contribution to the neurogenic hypertension pathophysiology. To investigate GHS-R1a role on renal function and hemodynamics, we used Wistar (WT) and spontaneously hypertensive rats (SHR). First, we assessed the effect of systemically injected vehicle, ghrelin, GHS-R1a antagonist PF04628935, ghrelin plus PF04628935 or GHS-R1a synthetic agonist MK-677 in WT and SHR rats housed in metabolic cages (24 h). Blood and urine samples were also analyzed. Then, we assessed the GHS-R1a contribution to the control of renal vasomotion and hemodynamics in WT and SHR. Finally, we assessed the GHS-R1a levels in brain areas, aorta, renal artery, renal cortex and medulla of WT and SHR rats using western blot. We found that ghrelin and MK-677 changed osmolarity parameters of SHR, in a GHS-R1a-dependent manner. GHS-R1a antagonism reduced the urinary Na + and K + and creatinine clearance in WT but not in SHR. Ghrelin reduced arterial pressure and increased renal artery conductance in SHR. GHS-R1a protein levels were decreased in the kidney and brain areas of SHR when compared to WT. Therefore, GHS-R1a role in the control of renal function and hemodynamics during neurogenic hypertension seem to be different, and this may be related to brain and kidney GHS-R1a downregulation., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aims: To test the hypothesis that experimental noxious stimulation of the right masseter muscle results in a reorganization of motor unit activity within the right temporalis and right masseter muscles during jaw closing tasks., Methods: A total of 20 healthy participants received hypertonic saline (5% sodium chloride) infusion into the right masseter muscle, and pain intensity was maintained at 40-60/100 mm on a visual analog scale. Standardized isometric biting tasks were performed with an intraoral force transducer while single motor units (SMUs) were recorded from the right masseter and temporalis muscles. Tasks were repeated in four blocks: block 1 (baseline 1), block 2 (hypertonic saline [HS] infusion or isotonic saline [IS] infusion), block 3 (infusion of the other solution), and block 4 (baseline 2). The occurrences of SMUs were tabulated across blocks. Statistical significance was considered to be P < .05., Results: There were no significant effects of block on the tasks. A total of 83 SMUs were discriminated in the temporalis and 58 in the masseter. For the comparison between HS and IS across tasks, the occurrences of 74.6% to 82.8% of SMUs were unchanged (70.2% to 94.3% for masseter), while during HS, 10.3% to 17.1% of SMUs were recruited (0% to 12.8%, masseter) and 6.9% to 12.7% were de-recruited (5.7% to 17%, masseter)., Conclusion: The present findings suggest that most biting-task-related jaw muscle SMUs remain active during experimental muscle noxious stimulation. There was some evidence in both the anterior temporalis and masseter muscles for motor unit recruitment and de-recruitment consistent with a motor unit reorganization during experimental pain.

Periaqueductal gray (PAG) is a midbrain region that projects to areas controlling behavioral and autonomic outputs and is involved in the behavioral and physiological components of defense reactions. Since Raphe Pallidus (RPa) is a medial medullary region comprising sympathetic premotor neurons governing heart function, it is worth considering the PAG-RPa path. We assessed: i) whether PAG projects to RPa; ii) the amplitude of cardiac responses evoked from PAG; iii) whether cardiovascular responses evoked from PAG rely on RPa. Experiments conducted in Wistar rats (±300 g) were approved by Ethics Committee CEUA-UFG (092/18). Firstly, (n = 3), monosynaptic retrograde tracer Retrobeads was injected into RPa; PAG slices were analyzed. Other two groups (n = 6 each) were anesthetized with urethane (1.4 g/kg) and chloralose (120 mg/kg) and underwent craniotomy, tracheostomy, catheterization of femoral artery and vein and of cardiac left ventricle. In one group, we injected the GABA A receptor antagonist, bicuculline methiodide (BMI - 40 pmol/100 nL) into lateral/dorsolateral PAG. Another group was injected (100 nL) with the GABA A receptor agonist muscimol (20 mM) into RPa, 20 min before BMI into PAG. The results were: i) retrogradely labelled neurons were found in PAG; ii) PAG activation by BMI caused positive chronotropism and inotropism, which were accompanied by afterload increases; iii) RPa inhibition with Muscimol reduced heart rate, arterial and ventricular pressures; iv) the subsequent PAG activation still increased arterial pressure, cardiac chronotropy and inotropy, but these responses were significantly attenuated. In conclusion, PAG activation increases cardiac chronotropy and inotropy, and these responses seem to rely on a direct pathway reaching ventromedial medullary RPa neurons., Competing Interests: Declaration of competing interest No conflicts of interest, financial or otherwise, are declared by the authors., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Biological invasion is one of the main threats to native biodiversity. For a species to become invasive, it must be voluntarily or involuntarily introduced by humans into a nonnative habitat. Mammals were among first taxa to be introduced worldwide for game, meat, and labor, yet the number of species introduced in the Neotropics remains unknown. In this data set, we make available occurrence and abundance data on mammal species that (1) transposed a geographical barrier and (2) were voluntarily or involuntarily introduced by humans into the Neotropics. Our data set is composed of 73,738 historical and current georeferenced records on alien mammal species of which around 96% correspond to occurrence data on 77 species belonging to eight orders and 26 families. Data cover 26 continental countries in the Neotropics, ranging from Mexico and its frontier regions (southern Florida and coastal-central Florida in the southeast United States) to Argentina, Paraguay, Chile, and Uruguay, and the 13 countries of Caribbean islands. Our data set also includes neotropical species (e.g., Callithrix sp., Myocastor coypus, Nasua nasua) considered alien in particular areas of Neotropics. The most numerous species in terms of records are from Bos sp. (n = 37,782), Sus scrofa (n = 6,730), and Canis familiaris (n = 10,084); 17 species were represented by only one record (e.g., Syncerus caffer, Cervus timorensis, Cervus unicolor, Canis latrans). Primates have the highest number of species in the data set (n = 20 species), partly because of uncertainties regarding taxonomic identification of the genera Callithrix, which includes the species Callithrix aurita, Callithrix flaviceps, Callithrix geoffroyi, Callithrix jacchus, Callithrix kuhlii, Callithrix penicillata, and their hybrids. This unique data set will be a valuable source of information on invasion risk assessments, biodiversity redistribution and conservation-related research. There are no copyright restrictions. Please cite this data paper when using the data in publications. We also request that researchers and teachers inform us on how they are using the data., (© 2020 The Authors. Ecology © 2020 The Ecological Society of America.)

Mammalian carnivores are considered a key group in maintaining ecological health and can indicate potential ecological integrity in landscapes where they occur. Carnivores also hold high conservation value and their habitat requirements can guide management and conservation plans. The order Carnivora has 84 species from 8 families in the Neotropical region: Canidae; Felidae; Mephitidae; Mustelidae; Otariidae; Phocidae; Procyonidae; and Ursidae. Herein, we include published and unpublished data on native terrestrial Neotropical carnivores (Canidae; Felidae; Mephitidae; Mustelidae; Procyonidae; and Ursidae). NEOTROPICAL CARNIVORES is a publicly available data set that includes 99,605 data entries from 35,511 unique georeferenced coordinates. Detection/non-detection and quantitative data were obtained from 1818 to 2018 by researchers, governmental agencies, non-governmental organizations, and private consultants. Data were collected using several methods including camera trapping, museum collections, roadkill, line transect, and opportunistic records. Literature (peer-reviewed and grey literature) from Portuguese, Spanish and English were incorporated in this compilation. Most of the data set consists of detection data entries (n = 79,343; 79.7%) but also includes non-detection data (n = 20,262; 20.3%). Of those, 43.3% also include count data (n = 43,151). The information available in NEOTROPICAL CARNIVORES will contribute to macroecological, ecological, and conservation questions in multiple spatio-temporal perspectives. As carnivores play key roles in trophic interactions, a better understanding of their distribution and habitat requirements are essential to establish conservation management plans and safeguard the future ecological health of Neotropical ecosystems. Our data paper, combined with other large-scale data sets, has great potential to clarify species distribution and related ecological processes within the Neotropics. There are no copyright restrictions and no restriction for using data from this data paper, as long as the data paper is cited as the source of the information used. We also request that users inform us of how they intend to use the data., (© 2020 The Authors. Ecology © 2020 The Ecological Society of America.)

Platelet-derived extracellular vesicles (PDEVs) are the most abundant amongst all types of EVs in the circulation. However, the mechanisms leading to PDEVs release, their role in coagulation and phenotypic composition are poorly understood. PDEVs from washed platelets were generated using different stimuli and were characterised using nanoparticle tracking analysis. Procoagulant properties were evaluated by fluorescence flow cytometry and calibrated automated thrombography. EVs from plasma were isolated and concentrated using a novel protocol involving a combination of size exclusion chromatography and differential centrifugation, which produces pure and concentrated EVs. Agonist stimulation enhanced PDEV release, but did not alter the average size of EVs compared to those produced by unstimulated platelets. Agonist stimulation led to lower negatively-charged phospholipid externalization in PDEVs, which was reflected in the lower procoagulant activity compared to those generated without agonist stimulation. Circulating EVs did not have externalized negatively-charged phospholipids. None of the 4 types of EVs presented tissue factor. The mechanism by which PDEV formation is induced is a critical determinant of its phenotype and function. Importantly, we have developed methods to obtain clean, concentrated and functional EVs derived from platelet-free plasma and washed platelets, which can be used to provide novel insight into their biological functions.

The lack of tissue selectivity of anticancer drugs generates intense collateral and adverse effects of cancer patients, making the incorporation of vitamins or micronutrients into the diet of individuals to reduce side or adverse effects of antineoplastics. The study aimed to evaluate the effects of retinol palmitate (RP) on the toxicogenic damages induced by cyclophosphamide (CPA), doxorubicin (DOX) and its association with the AC protocol (CPA + DOX), in Sarcoma 180 (S-180) tumor cell line, using the micronuclei test with a block of cytokinesis (CBMN); and in non-tumor cells derived from Mus musculus using the comet assay. The results suggest that CPA, DOX and AC protocol induced significant toxicogenic damages (P < 0.05) on the S-180 cells by induction of micronuclei, cytoplasmic bridges, nuclear buds, apoptosis, and cell necrosis, proving their antitumor effects, and significant damage (P < 0.001) to the genetic material of peripheral blood cells of healthy mice, proving the genotoxic potential of these drugs. However, RP modulated the toxicogenic effects of antineoplastic tested both in the CBMN test (P < 0.05), at the concentrations of 1, 10 and 100 IU/mL; as in the comet assay (P < 0.001) at the concentration of 100 IU/kg for the index and frequency of genotoxic damage. The accumulated results suggest that RP reduced the action of antineoplastics in non-tumor cells as well as the cytotoxic, mutagenic, and cell death in neoplastic cells., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Global climate change originates frequent floods that may cause severe damage, justifying the need for real-time remote monitoring and alerting systems. Several works deal with LoRa (Long Range) communications over land and in the presence of obstacles, but little is known about LoRa communication reliability over water, as it may happen in real flooding scenarios. One aspect that is known to influence the communication quality is the height at which nodes are placed. However, its impact in water environments is unknown. This is an important aspect that may influence the location of sensor nodes and the network topology. To fill this gap, we conducted several experiments using a real LoRa deployment to evaluate several features related to data communication. We considered two deployment scenarios corresponding to countryside and estuary environments. The nodes were placed at low heights, communicating, respectively, over the ground and over the water. Measurements for packet loss, received signal strength indicator (RSSI), signal-to-noise ratio (SNR) and round-trip time (RTT) were collected during a period of several weeks. Results for both scenarios are presented and compared in this paper. One important conclusion is that the communication distance and reliability are significantly affected by tides when the communication is done over the water and nodes are placed at low heights. Based on the RTT measurements and on the characteristics of the hardware, we also derive a battery lifetime estimation model that may be helpful for the definition of an adequate maintenance plan.

Background: Endothelium-derived prostacyclin and nitric oxide elevate platelet cyclic nucleotide levels and maintain quiescence. We previously demonstrated that a synergistic relationship exists between cyclic nucleotides and P2Y 12 receptor inhibition. A number of clinically approved drug classes can modulate cyclic nucleotide tone in platelets including activators of NO-sensitive guanylyl cyclase (GC) and phosphodiesterase (PDE) inhibitors. However, the doses required to inhibit platelets produce numerous side effects including headache., Objective: We investigated using GC-activators in combination with P2Y 12 receptor antagonists as a way to selectively amplify the anti-thrombotic effect of both drugs., Methods: In vitro light transmission aggregation and platelet adhesion under flow were performed on washed platelets and platelet rich plasma. Aggregation in whole blood and a ferric chloride-induced arterial thrombosis model were also performed., Results: The GC-activator BAY-70 potentiated the action of the P2Y 12 receptor inhibitor prasugrel active metabolite in aggregation and adhesion studies and was associated with raised intra-platelet cyclic nucleotide levels. Furthermore, mice administered sub-maximal doses of the GC activator cinaciguat together with the PDE inhibitor dipyridamole and prasugrel, showed significant inhibition of ex vivo platelet aggregation and significantly reduced in vivo arterial thrombosis in response to injury without alteration in basal carotid artery blood flow., Conclusions: Using in vitro, ex vivo, and in vivo functional studies, we show that low dose GC activators synergize with P2Y 12 inhibition to produce powerful anti-platelet effects without altering blood flow. Therefore, modulation of intra-platelet cyclic nucleotide levels alongside P2Y 12 inhibition can provide a strong, focused anti-thrombotic regimen while minimizing vasodilator side effects., (© 2020 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.)

Objectives: Anticholinergic drugs have several side effects, and they have been associated with adverse outcomes, particularly in older patients. The aim of this study was to analyze anticholinergic burden and its relationship to delirium and mortality in older acutely ill medical patients., Design: Cohort study., Setting and Participants: Patients 65 years of age and older who were admitted to an Internal Medicine ward between August 1 and December 31, 2016., Methods: Anticholinergic drug use, outpatient and inpatient, was assessed using the Anticholinergic Cognitive Burden Scale (ACB). Prevalent delirium was diagnosed by the Short Confusion Assessment Method (Short-CAM)., Results: Of the 198 patients, 28.3% developed delirium. Mortality rate was 13.6% in-hospital and 45.6% at 12 months. In multivariate analysis, outpatient ACB was associated with delirium, with an odds ratio (OR) of 1.65 [95% confidence interval (CI) 1.09-2.51]. Those with delirium had longer hospital stays (median 13 vs 8 days; P = .01), received more drugs (median 18 vs 15; P = .02), and presented a higher inpatient ACB (mean 3.9 vs 3.1; P = .034). No increased risk was found for in-hospital or 12-month mortality with drug use, ACB, or delirium., Discussion: In the population studied, we found an association between anticholinergic burden as measured by the ACB and the presence of delirium, but not with mortality at 12 months. A very high 12-month mortality rate might have been an obstacle for association recognition., Conclusions and Implications: Clinician awareness of possible drug side effects, especially in older populations, is crucial. As part of medication reconciliation at the time of hospitalization, ACB of prehospitalization medications should be routinely calculated by inpatient pharmacy services and made available to medical teams., (Copyright © 2019 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

This theoretical work investigates the properties of nonlinearly operated weakly coupled resonators (WCRs) for resonant sensing applications. We propose an analysis framework for mutually injection-locked oscillators (MILOs) and mode-localized oscillators (MOLOs), subject to nonlinear restoring and damping forces. Under some simplifying assumptions, three sensor architectures are investigated and compared, highlighting several common features, such as: 1) the insensitivity of the amplitude ratio output metric to the A-f effect and 2) the instability of one oscillation state above a threshold amplitude. These results are illustrated and validated using transient simulations. Their range of validity is then discussed with finite perturbations, finite bandwidth, measurement noise, and nonlinear dissipation-fluctuation.

The heptapeptide Bj-PRO-7a, isolated and identified from Bothrops jararaca (Bj) venom, produces antihypertensive and other cardiovascular effects that are independent on angiotensin converting enzyme inhibition, possibly relying on cholinergic muscarinic receptors subtype 1 (M1R). However, whether Bj-PRO-7a acts upon the central nervous system and modifies behavior is yet to be determined. Therefore, the aims of this study were: i) to assess the effects of acute administration of Bj-PRO-7a upon behavior; ii) to reveal mechanisms involved in the effects of Bj-PRO-7a upon locomotion/exploration, anxiety, and depression-like behaviors. For this purpose, adult male Wistar (WT, wild type) and spontaneous hypertensive rats (SHR) received intraperitoneal injections of vehicle (0.9% NaCl), diazepam (2 mg/kg), imipramine (15 mg/kg), Bj-PRO-7a (71, 213 or 426 nmol/kg), pirenzepine (852 nmol/kg), α-methyl-DL-tyrosine (200 mg/kg), or chlorpromazine (2 mg/kg), and underwent elevated plus maze, open field, and forced swimming tests. The heptapeptide promoted anxiolytic and antidepressant-like effects and increased locomotion/exploration. These effects of Bj-PRO-7a seem to be dependent on M1R activation and dopaminergic receptors and rely on catecholaminergic pathways.