Search

The ‘immune pattern’ of the esophagogastric junction and gastric cancer (GC) has been related to tumour progression and/or response to therapies. GC can be classified as immunogenic or immune-resistant based on the infiltration of the tumour microenvironment (TME) from different immune cells (ICs), the most significant of which are activated lymphocytes (a-Ly) CD8+ and CD4+. From the amount of a-Ly infiltration in TME, we can identify tumours with high Immunoscore (IS) which correlates with better prognosis in terms of disease-free survival and overall survival (OS). IC activation and consequent immunogenic TME requires high nutrient absorption and synthesis and accumulation of protein, lipid, and nucleotides. However, tumour cells (TCs) promote their own proliferation by stealing micronutrients to ICs, therefore leading to an immunosuppressive TME phenotype. This proof-of-concept protocol aims to assess whether a controlled enteral immune nutrition (EIN) supplementation can revert the TME in favour of ICs over TCs, in both auxotrophic and non-auxotrophic malignancies, witnessed by an increase in IS in surgical specimen over biopsy controls. Secondary endpoints are: (i) tumour regression grade assessment compared to historical data from FLOT4/AIO; (ii) combined proportion score ratio; (iii) relapse-free survival at 3 years and OS; and (iv) quality of life by the European Organisation for Research and Treatment of Cancer quality-of-life questionnaire (EORTC QLQ)-30.

In this study, we investigate the oscillations of relative sea level through the analysis of tide gauge records about 10-year long collected in the Gulfs of Pozzuoli and Napoli (Southern Italy). The main goal of this study is to provide a suitable resolution model of the sea tides including low frequency (seiches), tidal bands and non-linear tides. The spectral analyses of the tide gauge records lead us to identify a number of seiche periods some of them already known from the literature and some other unknown. Furthermore, we target a non-conventional purpose of the tidal analysis, namely extracting from the tide gauge records the volcano-tectonic signal (vertical ground displacement) in the resurgent Campi Flegrei caldera. We suggest a method to filter out the volcano-tectonic signal (bradyseism) from the tide gauge records by deconvolving it from two records, one collected in the active volcanic area (Pozzuoli) and the other one collected in a tectonically stable station (Napoli), located beyond the caldera rim. Finally, we retrieve the relative mean sea level change in the Gulf of Naples and compare it with the trend found in five tide gauges spread along the Italian coast.

In the last decades, a global warming trend was observed. Along with the temperature increase, modifications in the humidity and wind regime amplify the regional and local impacts on livestock husbandry. Direct impacts include the occurrence of climatic stress conditions. In Europe, cows are economically highly relevant and are mainly kept in naturally ventilated buildings that are most susceptible to climate change. The high-yielding cows are particularly vulnerable to heat stress. Modifications in housing management are the main measures taken to improve the ability of livestock to cope with these conditions. Measures are typically taken in direct reaction to uncomfortable conditions instead of in anticipation of a long-term risk for climatic stress. Measures that balance welfare, environmental and economic issues are barely investigated in the context of climate change and are thus almost not available for commercial farms. Quantitative analysis of the climate change impacts on animal welfare and linked economic and environmental factors is rare. Therefore, we used a numerical modeling approach to estimate the future heat stress risk in such dairy cattle husbandry systems. The indoor climate was monitored inside three reference barns in central Europe and the Mediterranean regions. An artificial neuronal network (ANN) was trained to relate the outdoor weather conditions provided by official meteorological weather stations to the measured indoor microclimate. Subsequently, this ANN model was driven by an ensemble of regional climate model projections with three different greenhouse gas concentration scenarios. For the evaluation of the heat stress risk, we considered the number and duration of heat stress events. Based on the changes in the heat stress events, various economic and environmental impacts were estimated. The impacts of the projected increase in heat stress risk varied among the barns due to different locations and designs as well as the anticipated climate change (considering different climate models and future greenhouse gas concentrations). There was an overall increasing trend in number and duration of heat stress events. At the end of the century, the number of annual stress events can be expected to increase by up to 2000, while the average duration of the events increases by up to 22 h compared to the end of the last century. This implies strong impacts on economics, environment and animal welfare and an urgent need for mid-term adaptation strategies. We anticipated that up to one-tenth of all hours of a year, correspondingly one-third of all days, will be classified as critical heat stress conditions. Due to heat stress, milk yield may decrease by about 2.8 % relative to the present European milk yield, and farmers may expect financial losses in the summer season of about 5.4 % of their monthly income. In addition, an increasing demand for emission reduction measures must be expected, as an emission increase of about 16 Gg of ammonia and 0.1 Gg of methane per year can be expected under the anticipated heat stress conditions. The cattle respiration rate increases by up to 60 %, and the standing time may be prolonged by 1 h. This causes health issues and increases the probability of medical treatments. The various impacts imply feedback loops in the climate system which are presently underexplored. Hence, future in-depth studies on the different impacts and adaptation options at different stress levels are highly recommended.

Technological progress enables individual cow's temperatures to be measured in real time, using a bolus sensor inserted into the rumen (reticulorumen). However, current cooling systems often work at a constant schedule based on the ambient temperature and not on monitoring the animal itself. This study hypothesized that tailoring the cooling management to the cow's thermal reaction can mitigate heat stress. We propose a dynamic cooling system based on in vivo temperature sensors (boluses). Thus, cooling can be activated as needed and is thus most efficacious. A total of 30 lactating cows were randomly assigned to one of two groups; the groups received two different evaporative cooling regimes. A control group received cooling sessions on a preset time-based schedule, the method commonly used in farms; and an experimental group, which received the sensor-based (SB) cooling regime. Sensor-based was changed weekly according to the cow's reaction, as reflected in the changes in body temperatures from the previous week, as measured by reticulorumen boluses. The two treatment groups of cows had similar milk yields (44.7 kg/d), but those in the experimental group had higher milk fat (3.65 vs 3.43%), higher milk protein (3.23 vs 3.13%), higher energy corrected milk (ECM, 42.84 vs 41.48 kg/d), higher fat corrected milk 4%; (42.76 vs 41.34 kg/d), and shorter heat stress duration (5.03 vs 9.46 h/day) comparing to the control. Dry matter intake was higher in the experimental group. Daily visits to the feed trough were less frequent, with each visit lasting longer. The sensor-based cooling regime may be an effective tool to detect and ease heat stress in high-producing dairy cows during transitional seasons when heat load can become severe in arid and semi-arid zones.

Understanding processes responsible for shaping biodiversity patterns on continental margins is an important requirement for comprehending anthropogenic impacts in these environments and further management of biodiversity. Continental margins perform crucial functions linked to key ecological processes which are mainly structured by surface primary productivity and particulate organic matter flux to the seafloor, but also by heterogeneity in seafloor characteristics. However, to what extent these processes control local and regional biodiversity remains unclear. In this study, two isobathic parallel transects located at the shelf break (300–400 m) and upper slope (1000 m) of the western Iberian margin were used to test how food input and sediment heterogeneity affect nematode diversity independently from the spatial factors geographical distance and water depth. We also examined the potential role of connectedness between both depth transects through molecular phylogenetic analyses. Regional generic diversity and turnover were investigated at three levels: within a station, between stations from the same depth transect, and between transects. High variability in food availability and high sediment heterogeneity at the shelf-break transect were directly linked to high diversity within stations and higher variation in community structure across stations compared to the upper slope transect. Contrastingly, environmental factors (food availability and sediment) did not vary significantly between stations located at the upper slope, and this lack of differences were also reflected in a low community turnover between these deeper stations. Finally, differences in nematode communities between both transects were more pronounced than differences within each of the isobathic transects, but these changes were paralleled by the previously mentioned environmental changes. These results suggest that changes in community structure are mainly dictated by environmental factors rather than spatial differences at the western Iberian margin. Furthermore, phylogenetic relationships revealed no evidence for depth-endemic lineages, indicating regular species interchanges across different depths.

Abstract N-acylhydrazones are considered privileged structures in medicinal chemistry, being part of antimicrobial compounds (for example). In this study we show the activity of N-acylhydrazone compounds, namely AH1, AH2, AH4, AH5 in in vitro tests against the chloroquine-resistant strain of Plasmodium falciparum (W2) and against WI26 VA-4 human cell lines. All compounds showed low cytotoxicity (LC50 > 100 µM). The AH5 compound was the most active against Plasmodium falciparum, with an IC50 value of 0.07 μM. AH4 and AH5 were selected among the tested compounds for molecular docking calculations to elucidate possible targets involved in their mechanism of action and the SwissADME analysis to predict their pharmacokinetic profile. The AH5 compound showed affinity for 12 targets with low selectivity, while the AH4 compound had greater affinity for only one target (3PHC). These compounds met Lipinski's standards in the ADME in silico tests, indicating good bioavailability results. These results demonstrate that these N-acylhydrazone compounds are good candidates for future preclinical studies against malaria. Graphical Abstract

The current COVID-19 pandemic raises several clinical challenges. Cases of COVID-19-associated arthritis have been reported, and inconsistently described as either COVID-19 viral arthritis or COVID-19 reactive arthritis. We aimed to review all the reported cases of ‘COVID-19-associated arthritis’, which we propose, is a better term to define the entire spectrum of new-onset arthritis believed to be associated with SARS-CoV-2 infection. We performed a systematic literature review using MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews to search for articles published up to 13 December 2021. We included cohort studies, case series and case reports describing patients diagnosed with COVID-19 reactive or viral arthritis by a physician, irrespective of fulfilment of classification criteria. To identify relevant studies, medical subject headings and keywords related to ‘COVID-19/SARS-CoV-2 infection’ and ‘reactive arthritis’ were used. Our search retrieved 419 articles, of which 31 were included in the review. A total of 33 cases were reported in these 31 articles, the majority being adults (28/33=85%) with peripheral joint involvement (26/33=79%). Most of the patients responded well to treatment and the disease was self-limiting. These 33 case reports describe a possible causal relationship between exposure to SARS-CoV-2 and the onset of arthritis. However, since these cases were reported during a pandemic, other aetiologies cannot be fully excluded. The exact mechanism through which SARS-CoV-2 might trigger arthritis is not fully understood and robust epidemiological data to support a causal relationship are still lacking.

IntroductionTranscranial magnetic stimulation (TMS) is a consolidated procedure for the treatment of depression, with several meta-analyses demonstrating its efficacy. Theta-burst stimulation (TBS) is a modification of TMS with similar efficacy and shorter session duration. The geriatric population has many comorbidities and a high prevalence of depression, but few clinical trials are conducted specifically for this age group. TBS could be an option in this population, offering the advantages of few side effects and no pharmacological interactions. Therefore, our aim is to investigate the efficacy of TBS in geriatric depression.Clinical trial registration[https://clinicaltrials.gov/ct2/], identifier [NCT04842929].

Introduction: The dissemination of the COVID-19 pandemic in Europe, namely in Portugal, demanded an organizational and clinical reaction from the Portuguese National Health Service. With the unpredictable impact of COVID-19 infected patients redefining hospital logistics, reducing non-priority elective care and extending the hospital capacity for critical care patients made mobilizing a significant part of human resources a priority. We conducted a national survey to monitor the contribution and the role of anaesthesiologists belonging to the 53 Portuguese National Health Service hospitals in the first wave fight against the pandemic. Material and Methods: This prospective cross-sectional observational study used a weekly survey sent to the Directors of the Anaesthesiology Departments of all Portuguese National Health Service hospitals, between the period of 13th April and 21st June 2020. Directors were asked about human resources, hospital logistics, anaesthetic activity and residency programs in their departments as well as contingency plans facing the impact of the pandemic growth in the PNHS. Results: Contingency strategy for all Portuguese National Health Service hospitals planned for a total of 1524 level III critical care beds during the initial phases of the pandemic, an increase of 151% from the existing 607 level III critical care beds in Portugal in January 2020. This re-configuration effort of the Portuguese National Health Service was only possible due to the partial or total suspension of non-urgent elective activity that reached over 90% of these institutions in the first pandemic months (March and April) and the deployment of anaesthesiologists from their normal activities to the treatment of critical care patients. During the peak of the first pandemic wave, 209 anaesthesiology specialists and 170 trainees (22.9% of the total anaesthesiologist’s staff in the Portuguese National Health Service) were deployed in critical care. There was an almost complete interruption of the residency program rotation in 70.4% of hospitals with anaesthesiology residents, between March and April 2020. Conclusion: During the first pandemic wave there was an effective and fast reorganisation of the Portuguese National Health Service in order to increase level III critical care beds, which might have contributed to the low mortality rates in Portugal. We believe that this could have also been a result of the contribution given by all public anaesthesiology departments.

Abstract With increased interest in cultivation, the study of white-fleshed pitahaya (Selenicereus undatus (Haw.) D.R. Hunt, Cactaceae family) seedling production is of fundamental importance in the search for novel techniques to increase cultivation and guarantee homogeneous and productive orchards. The present study investigated the influence of various gibberellic acid (GA3) concentrations and fruit maturation stages on seed germination and vigor of white-fleshed pitahaya seedlings, considering the physiological quality of seedlings produced to support genetic breeding and conservation programs of the species. White-fleshed pitahaya seeds at two maturation stages (physiologically ripe and maintained at 10 °C in Biochemical Oxygen Demand incubators for three months) were treated with varying GA3 concentrations of 0, 50, 100, and 500 mg/L. We observed the influence of fruit storage on seedling germination, emergence, and growth as a function of GA3 concentration. According to the results, seeds extracted from ripe white-fleshed pitahaya fruits grown under the conditions tested here required GA3 application to increase seedling emergence and vigor, with optimal doses in the 150–300-mg/L range. In the case of pitahaya fruits intended for storage for future seed removal and maintained under the same sowing conditions, the application of higher doses of GA3 was necessary when compared to the previous condition, with a minimum dose of 500 mg/L GA3. The present study shows that the maturation stage of white-fleshed pitahaya fruits intended for seed removal influences the quality of seedlings; therefore, the use of seeds extracted from ripe pitahaya fruits without fermentation is more appropriate for the purpose.

Nicotinamide adenine dinucleotide (NAD+) is an essential pyridine nucleotide cofactor that is present in cells and in several important biological processes, including oxidative phosphorylation and production of adenosine triphosphate, DNA repair, calcium-dependent secondary messenger and gene expression. The purpose of this systematic review is to examine whether the coenzyme formulae NADþ and NADH are safe and effective when acting as a supplement to humans. This systematic review of randomized clinical trials performed a search in six electronic databases: PubMed, MEDLINE (ovid), Embase, Cochrane CENTRAL (clinical trials), Web of Science, and Scopus. Secondary search included the databases (e.g., Clinical trials.gov, Rebec, Google Scholar - advance). Two reviewers assessed and extracted the studies independently. The risk of bias in studies was performed using version 2 of the Cochrane risk of bias tool for randomized trials. This review includes 10 studies, with a total of 489 participants. The studies included different clinical conditions, such as chronic fatigue syndrome (CFS), older adults, Parkinson's disease, overweight, postmenopausal prediabetes, and Alzheimer's disease. Based on studies, the supplementation with NADH and precursors was well tolerated and observed clinical results such as, a decrease in anxiety conditions and maximum heart rate was observed after a stress test, increased muscle insulin sensitivity, insulin signaling. Quality of life, fatigue intensity, and sleep quality among others were evaluated on patients with CFS. All studies showed some side effects, thus, the most common associated with NADs use are muscle pain, nervous disorders, fatigue, sleep disturbance, and headaches. All adverse events cataloged by the studies did not present a serious risk to the health of the participants. Overall, these findings support that the oral administration of NADH can be associated to an increase in general quality of life and improvement on health parameters (e.g., a decrease in anxiety, maximum heart rate, inflammatory cytokines in serum, and cerebrospinal fluid). NADH supplementation is safe and has a low incidence of side effects. Future investigations are needed to evidence the clinical benefits regarding specific diseases and doses administered. [ABSTRACT FROM AUTHOR]

Abstract The hamstrings-to-quadriceps muscle strength ratio calculated by peak torque has been used as an important tool to detect muscle imbalance, monitor knee joint stability, describe muscle strength properties and functionality, and for lower extremity injury prevention and rehabilitation. However, this ratio does not consider other neuromuscular variables that can also influence the antagonist to agonist muscle relationship, such as torque produced at multiple angles of range of motion, explosive strength, muscle size, muscle fatigue, or muscle activation. The aim of this study was to comprehensively review alternative methods of determining the hamstrings-to-quadriceps ratio. These include ratios calculated by angle-specific torque, rate of torque development, muscle size, fatigue index, and muscle activation (measured by electromyography). Collectively, the literature demonstrates that utilizing alternative methods of determining the hamstrings-to-quadriceps ratio can be functionally relevant for a better understanding of the neuromuscular mechanisms underpinning the interaction of strength between hamstrings and quadriceps. However, there is insufficient evidence to recommend any of the alternative methods as sensitive clinical tools for predicting injury risk and monitoring knee joint integrity. Future longitudinal studies, along with injury incidence, are needed to further investigate all alternative methods of determining the hamstrings-to-quadriceps ratio. These have potential to offer insight into how athletes and the general population should be trained for performance enhancement and injury reduction, and may be used along with traditional methods for a thorough assessment of an individual’s H:Q muscle balance.

The leakage current (LC) caused by the surface contamination of insulators, together with environmental variables, is one of the most basic online monitoring parameters for insulator status. However, the impact of weather conditions such as temperature, air humidity, and dew point on the LC has not been deeply studied until now. In this paper, based on meteorological data obtained online and LC obtained with an optical fiber sensor, installed in 500-kV insulator strings of a transmission line, the impact of weather conditions was studied. Results indicate that the LCs follow a specific pattern, according to weather conditions. The system has been continuously monitoring LC, humidity, temperature, and dew point uninterrupted for three years, sending the acquired data to a web page; therefore, it has been demonstrated to be robust, reliable, and repetitive. The sensor features the broadband response and acquisition capabilities of partial discharge pulses in high-voltage insulators, allowing the detection of high-frequency pulses. When comparing the LC measured in this work with those from other works, our measurements are substantially higher; this is due to the type of pollution found in this specific situation, which includes iron oxide powder, producing a conductive layer over the insulator surface that, unlike sea salt, does not depend on humidity to conduct an LC. One of the conclusions reached in this work is that partial discharge surges are caused when the local temperature reaches the dew point and not simply from the presence of high humidity, as stated in many works dealing with LCs. The monitored LC can be used as an indicative parameter of a possible flashover, enabling the proper planning of insulator predictive maintenance, either by jet-washing the surface or even changing the insulators when they are damaged.

Distribution networks have undergone a series of changes, with the insertion of distributed energy resources, such as distributed generation, energy storage systems, and demand response, allowing the consumers to produce energy and have an active role in distribution systems. Thus, it is possible to form microgrids. From the active grid’s point of view, it is necessary to plan the operation considering the distributed resources and the microgrids connected to it, aiming to ensure the maintenance of grid economy and operational safety. So, this paper presents the proposition of a hierarchical model for planning the daily operation of active distribution grids with microgrids. In this case, the entire grid operation is optimized considering the results from the microgrid optimization itself. If none of the technical constraints, for example voltage levels, are reached, the grid is optimized, however, if there are some violations in the constraints feedback is sent to the internal microgrid optimization to be run again. Several scenarios are evaluated to verify the iteration among the controls in a coordinated way allowing the optimization of the operation of microgrids, as well as of the distribution network. A coordinated and hierarchical operation of active distribution networks with microgrids, specifically when they have distributed energy resources allocated and operated in an optimized way, results in a reduction in operating costs, losses, and greater flexibility and security of the whole system.

Eugenol, 4-allyl-2-methoxyphenol, is the main constituent of clove essential oil and has demonstrated relevant biological activity, namely anticancer activity. Aiming to increase this activity, we synthesized a series of eugenol β-amino alcohol and β-alkoxy alcohol derivatives, which were then tested against two human cancer cell lines, namely gastric adenocarcinoma cells (AGS) and lung adenocarcinoma cells (A549). An initial screening was performed to identify the most cytotoxic compounds. The results demonstrated that three β-amino alcohol derivatives had anticancer activity that justified subsequent studies, having been shown to trigger apoptosis. Importantly, the most potent molecules displayed no appreciable toxicity towards human noncancer cells. Structure-activity relationships show that changes in eugenol structure led to enhanced cytotoxic activity and can contribute to the future design of more potent and selective drugs.

Background We systematically reviewed trials comparing different reperfusion strategies for ST‐segment–elevation myocardial infarction and used multivariate network meta‐analysis to compare outcomes across these strategies. Methods and Results We identified 31 contemporary trials in which patients with ST‐segment–elevation myocardial infarction were randomized to ≥2 of the following strategies: fibrinolytic therapy (n=4212), primary percutaneous coronary intervention (PCI) (n=6139), or fibrinolysis followed by routine early PCI (n=5006). We categorized the last approach as “facilitated PCI” when the median time interval between fibrinolysis to PCI was

Background Intravascular ultrasound (IVUS) guidance during percutaneous coronary intervention (PCI) offers tomographic images of the coronary vessels, allowing optimization of stent implantation at the time of PCI. However, the long‐term beneficial effect of IVUS over PCI guided by coronary angiography (CA) alone remains under question. We sought to investigate the outcomes of IVUS‐guided compared with CA‐guided PCI. Methods and Results We performed a comprehensive search of PubMed, Medline, and Cochrane Central Register, looking for randomized controlled trials and observational studies that compared PCI outcomes of IVUS with CA. Data were aggregated for the primary outcome measure using the random‐effects model as pooled risk ratio (RR). The primary outcomes were the rate of cardiovascular death, need for target lesion revascularization, occurrence of myocardial infarction, and rate of stent thrombosis. A total of 19 studies met the inclusion criteria, comprising 27 610 patients divided into IVUS (n=11 513) and CA (n=16 097). Compared with standard CA‐guided PCI, we found that the risks of cardiovascular death (RR, 0.63; 95% CI, 0.54–0.73), myocardial infarction (RR, 0.71; 95% CI, 0.58–0.86), target lesion revascularization (RR, 0.81; 95% CI, 0.70–0.94), and stent thrombosis (RR, 0.57; 95% CI, 0.41–0.79) were all significantly lower using IVUS guidance. Conclusions Compared with standard CA‐guided PCI, the use of IVUS imaging guidance to optimize stent implantation is associated with a reduced risk of cardiovascular death and major adverse events, such as myocardial infarction, target lesion revascularization, and stent thrombosis.

The purpose of the present study was to compare the heart rate (HR), blood lactate and training load between different CrossFit® workouts, with equalized total work volumes in men and women. The study included 23 individuals (13 men and 10 women) experienced in CrossFit® training, who performed two workouts with different training types (as many reps as possible (AMRAP) and ‘for time’) but an equalized volume. Measurements of lactate, HR and rating of perceived exertion (RPE) were performed. The results show that there was no HR interaction between workout time and sex (p = 0.822; η2 = 0.006) and between workout type and sex (p = 0.064, η2 = 0.803). The HR significantly differed during each workout type (p < 0.001, η2 = 0.621), but not between the two workout types (p = 0.552, η2 = 0.017). Lactate showed no difference between the workout types (p = 0.474, η2 = 0.768), although the training load was higher (p = 0.033, η2 = 0.199) in women when they performed AMRAP. Altogether, the HR was not significantly different between training types or sex, while RPE, lactate and training load showed statistically significant differences depending on the group (women or men) or workout type (AMRAP or ‘for time’).