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The Douro Demarcated Region (DDR) has peculiar edaphoclimatic characteristics that provide a suitable terroir for premium wine production. As climate change effects continue to emerge, ensuring productivity and quality becomes increasingly important for viticulturists, as those directly determine their profits. Cultural approaches, such as the use of biostimulants, are actively being developed to mitigate abiotic stress. The main objective of this work was to assess the effect of foliar sprays of a seaweed (Ascophyllum nodosum)-based extract (ANE) and glycine betaine (GB) on grape berry quality, bioactive compounds, and antioxidant activity. A trial was installed in a commercial vineyard (cv. ‘Touriga Franca’) in the Douro Superior (Upper Douro) sub-region of the Douro Demarcated Region. In 2020 and 2021, three foliar sprayings were performed during the growing season, namely at pea size, bunch closure, and veraison. There was a positive effect of both biostimulants (ANE and GB) on the physiological and biochemical performance of cv. ‘Touriga Franca’ exposed to summer stress. In general, the GB 0.2% spraying was the most promising treatment for this grape cultivar, as it increased berry quality, the concentration of bioactive compounds (total phenolics, flavonoids, and ortho-diphenols), and the antioxidant activity. These results revealed the efficacy of biostimulant sprayings as a sustainable viticultural practice, improving berry quality under summer stress conditions.

Consumption of antimicrobials is an important driver of antimicrobial resistance. There is limited knowledge of the key determinants of antimicrobial prescribing behavior in hospitals. An understanding of these determinants is required for the successful design, adoption, and implementation of quality improvement interventions in Antimicrobial Stewardship Programs (ASP). This study aimed to describe the main factors that influence the doctor’s decision on antimicrobials prescribing and to identify the behaviors that drive physicians’ decision making. A structured web-based questionnaire focused on behavioral components of antimicrobial prescription was applied to the medical staff of three different departments—Internal Medicine, General Surgery, and Intensive Care Medicine—of a university hospital. All doctors agreed that inadequate use of antimicrobials increases AMR. A total of 77% of the surgeons and 100% of the internists and intensivists perceived antimicrobial prescription as a priority in the department. Full autonomy in antimicrobial prescription was preferred by internists (64%) but not by surgeons (18%) and intensivists (24%). Most physicians were keen to have ASP advice, but most did not want advice from colleagues of the same service. Almost all surgeons ask for advice when prescribing, but only 68% of the internists do it. Less than half of all physicians and only 25% of the surgeons felt free to prescribe contrary to guidelines. Most physicians, particularly in Intensive Care Medicine (94%), adopt the “wait and see” strategy when no microbiologic confirmation is available, but 27% of the surgeons start empirical therapy. In conclusion, the context of antimicrobial prescription, autonomy, and confidence in antimicrobial prescription demonstrated heterogeneity between the three departments and this should be considered when planning ASP.

The deep-sea constitutes a true unexplored frontier and a potential source of innovative drug scaffolds. Here, we present the genome sequence of two novel marine actinobacterial strains, MA3_2.13 and S07_1.15, isolated from deep-sea samples (sediments and sponge) and collected at Madeira archipelago (NE Atlantic Ocean; Portugal). The de novo assembly of both genomes was achieved using a hybrid strategy that combines short-reads (Illumina) and long-reads (PacBio) sequencing data. Phylogenetic analyses showed that strain MA3_2.13 is a new species of the Streptomyces genus, whereas strain S07_1.15 is closely related to the type strain of Streptomyces xinghaiensis. In silico analysis revealed that the total length of predicted biosynthetic gene clusters (BGCs) accounted for a high percentage of the MA3_2.13 genome, with several potential new metabolites identified. Strain S07_1.15 had, with a few exceptions, a predicted metabolic profile similar to S. xinghaiensis. In this work, we implemented a straightforward approach for generating high-quality genomes of new bacterial isolates and analyse in silico their potential to produce novel NPs. The inclusion of these in silico dereplication steps allows to minimize the rediscovery rates of traditional natural products screening methodologies and expedite the drug discovery process.

As the world develops and population increases, so too does the demand for higher agricultural output with lower resources. Plant biostimulants appear to be one of the more prominent sustainable solutions, given their natural origin and their potential to substitute conventional methods in agriculture. Classified based on their source rather than constitution, biostimulants such as humic substances (HS), protein hydrolysates (PHs), seaweed extracts (SWE) and microorganisms have a proven potential in improving plant growth, increasing crop production and quality, as well as ameliorating stress effects. However, the multi-molecular nature and varying composition of commercially available biostimulants presents challenges when attempting to elucidate their underlying mechanisms. While most research has focused on the broad effects of biostimulants in crops, recent studies at the molecular level have started to unravel the pathways triggered by certain products at the cellular and gene level. Understanding the molecular influences involved could lead to further refinement of these treatments. This review comprises the most recent findings regarding the use of biostimulants in plants, with particular focus on reports of their molecular influence.

Background: The COVID-19 pandemic poses novel challenges in antimicrobial consumption metrics and stewardship strategies. COVID-19 patients became the major cause of hospital admission during the first wave of the pandemic, often leading to an antimicrobial prescription upon admission or treatment for superinfections. The aim of this study was to understand how antimicrobial consumption was impacted at the beginning of the pandemic in a tertiary care hospital, a reference center for COVID-19. Materials and Methods: A retrospective before-and-after study was done. Descriptive statistics of discharges, patient-days, and antimicrobial use indicators (defined daily doses (DDD)/100 discharges, DDD/100 patient-days) for various groups were calculated for the first three months of the pandemic (March, April, and May 2020) as a quarterly value, and for each year in 2011–2019, and their annual percentage changes were used to estimate 95% confidence intervals. The indicators were compared to patient type (medical/surgical), type of admission (urgent/elective), and age groups using Spearman’s correlation coefficient. Results: Statistically significant increases occurred in 2020 for total antibacterials, macrolides, cephalosporins, amoxicillin/clavulanic acid, carbapenems, meropenem, and third-generation cephalosporins, while a reduction was seen in cefazolin/cefoxitin. A correlation was found between antibacterial consumption and patient or admission type. In 2020, unlike in pre-pandemic years, there was a different impact in DDD/100 discharges and DDD/100 patient-days due to increased lengths-of-stay and longer antimicrobial therapy. Conclusions: The COVID-19 pandemic led to an increase in antimicrobial consumption with a different impact in DDD/100 discharges and DDD/100 patient-days. This highlights the need to use both indicators simultaneously to better understand the causes of antimicrobial consumption variation and improve the design of effective antimicrobial stewardship interventions.

Cracking of sweet cherry (Prunus avium L.) fruits is caused by rain events close to harvest. This problem has occurred in most cherry growing regions with significant economic losses. Several orchard management practices have been applied to reduce the severity of this disorder, like the foliar application of minerals or growth regulators. In the present study, we hypothesized that preharvest spray treatments improve the physiological performance of sweet cherry trees and could also mitigate environmental stressful conditions. Effects of repeated foliar spraying of calcium (Ca), gibberellic acid (GA3), abscisic acid (ABA), salicylic acid (SA), glycine betaine (GB), and the biostimulant Ascophyllum nodosum (AN) on the physiological and biochemical performance of ‘Skeena’ sweet cherry trees during two consecutive years (without Ca in 2015 and in 2016 with addition of Ca) were studied. Results showed that in general spray treatments improved the physiological performance and water status of the trees. AN and ABA sprays were demonstrated to be the best compounds for increasing yield and reducing cherry cracking as well as improving photosynthetic performance and leaf metabolites content. In conclusion, AN and ABA might be promising tools in the fruit production system.

Depression is a prevalent, socially burdensome disease. Different studies have demonstrated the important role of astrocytes in the pathophysiology of depression as modulators of neurotransmission and neurovascular coupling. This is evidenced by astrocyte impairments observed in brains of depressed patients and the appearance of depressive-like behaviors upon astrocytic dysfunctions in animal models. However, little is known about the importance of de novo generated astrocytes in the mammalian brain and in particular its possible involvement in the precipitation of depression and in the therapeutic actions of current antidepressants (ADs). Therefore, we studied the modulation of astrocytes and adult astrogliogenesis in the hippocampal dentate gyrus (DG) of rats exposed to an unpredictable chronic mild stress (uCMS) protocol, untreated and treated for two weeks with antidepressants—fluoxetine and imipramine. Our results show that adult astrogliogenesis in the DG is modulated by stress and imipramine. This study reveals that distinct classes of ADs impact differently in the astrogliogenic process, showing different cellular mechanisms relevant to the recovery from behavioral deficits induced by chronic stress exposure. As such, in addition to those resident, the newborn astrocytes in the hippocampal DG might also be promising therapeutic targets for future therapies in the neuropsychiatric field.

The low regeneration potential of the central nervous system (CNS) represents a challenge for the development of new therapeutic strategies for neurodegenerative diseases, including spinocerebellar ataxias. Spinocerebellar ataxia type 3 (SCA3)—or Machado–Joseph disease (MJD)—is the most common dominant ataxia, being mainly characterized by motor deficits; however, SCA3/MJD has a complex and heterogeneous pathophysiology, involving many CNS brain regions, contributing to the lack of effective therapies. Mesenchymal stem cells (MSCs) have been proposed as a potential therapeutic tool for CNS disorders. Beyond their differentiation potential, MSCs secrete a broad range of neuroregulatory factors that can promote relevant neuroprotective and immunomodulatory actions in different pathophysiological contexts. The objective of this work was to study the effects of (1) human MSC transplantation and (2) human MSC secretome (CM) administration on disease progression in vivo, using the CMVMJD135 mouse model of SCA3/MJD. Our results showed that a single CM administration was more beneficial than MSC transplantation—particularly in the cerebellum and basal ganglia—while no motor improvement was observed when these cell-based therapeutic approaches were applied in the spinal cord. However, the effects observed were mild and transient, suggesting that continuous or repeated administration would be needed, which should be further tested.