Effects of feeding with a protein liquid supplement on productivity, mortality and health of Apis mellifera hives in southwestern Spain.

Colony collapse disorder (CCD) has affected bees worldwide in recent decades, with southwestern Spain being no exception. This disorder is one of the main causes of Apis mellifera mortality and is believed to be caused by environmental, social and sanitary conditions. Dietary supplementation can help to improve some parameters of the general status and sanitary condition of bees, such as infestation by certain recurrent pathogens, including Varroa destructor and Nosema ceranae, by enhancing immune and social response. Thus, the aim of this study was to test a liquid hydrolysed protein supplement on the health and general status of the hive in several apiaries with access to the same natural food and under similar climatic conditions. We selected two groups of ten hives (supplemented by either placebo or protein) from five apiaries where the number of adult bees, amount of brood (open and operculated), honey and pollen reserves, infestation by V. destructor, N. ceranae, deformed wing virus (DWV) and chronic bee paralysis virus (CBPV) were measured. Additionally, we assess the expression of four immune system-related genes and a gene encoding vitellogenin. At the end of this work, treated hives showed a significant increase in open brood and a decrease in V. destructor infestation. Also, these hives showed a significant decrease in the mortality rate after the cold season. Therefore, supplementation with this product improved the health of the hive and could be a promising tool against bee colony loss.

Genetic architecture of acute hyperthermia resistance in juvenile rainbow trout (Oncorhynchus mykiss) and genetic correlations with production traits.

BACKGROUND: Selective breeding is a promising solution to reduce the vulnerability of fish farms to heat waves, which are predicted to increase in intensity and frequency. However, limited information about the genetic architecture of acute hyperthermia resistance in fish is available. Two batches of sibs from a rainbow trout commercial line were produced: the first (N = 1382) was phenotyped for acute hyperthermia resistance at nine months of age and the second (N = 1506) was phenotyped for main production traits (growth, body length, muscle fat content and carcass yield) at 20 months of age. Fish were genotyped on a 57 K single nucleotide polymorphism (SNP) array and their genotypes were imputed to high-density based on the parent's genotypes from a 665 K SNP array. RESULTS: The heritability estimate of resistance to acute hyperthermia was 0.29 ± 0.05, confirming the potential of selective breeding for this trait. Since genetic correlations of acute hyperthermia resistance with the main production traits near harvest age were all close to zero, selecting for acute hyperthermia resistance should not impact the main production traits, and vice-versa. A genome-wide association study revealed that resistance to acute hyperthermia is a highly polygenic trait, with six quantitative trait loci (QTL) detected, but explaining less than 5% of the genetic variance. Two of these QTL, including the most significant one, may explain differences in acute hyperthermia resistance across INRAE isogenic lines of rainbow trout. Differences in mean acute hyperthermia resistance phenotypes between homozygotes at the most significant SNP was 69% of the phenotypic standard deviation, showing promising potential for marker-assisted selection. We identified 89 candidate genes within the QTL regions, among which the most convincing functional candidates are dnajc7, hsp70b, nkiras2, cdk12, phb, fkbp10, ddx5, cygb1, enpp7, pdhx and acly. CONCLUSIONS: This study provides valuable insight into the genetic architecture of acute hyperthermia resistance in juvenile rainbow trout. We show that the selection potential for this trait is substantial and selection for this trait should not be too detrimental to improvement of other traits of interest. Identified functional candidate genes provide new knowledge on the physiological mechanisms involved in acute hyperthermia resistance, such as protein chaperoning, oxidative stress response, homeostasis maintenance and cell survival.

Effect of feed supplementation with probiotics and postbiotics on strength and health status of honey bee (Apis mellifera) hives during late spring.

Currently, beekeeping faces many risks, such as deteriorating health of honeybees in hives, which results in high mortality rates, mainly during winter. An important consequence is the emergence/re-emergence of communicable diseases such as varroosis or nosemosis. These diseases jeopardize the continuity of the sector because of the absence of effective treatments and harmful residues that they can be retained on wax or honey. This study aimed to evaluate how feed supplementation with probiotic and postbiotic products derived from lactic acid bacteria affected the strength, dynamic population, and sanitary parameters of honey bees. Three groups of 30 hives were established and fed with feed supplemented with control, probiotic, or postbiotic products, with a total of nine applications over two months in late spring. Two monitoring tests were conducted to evaluate the strength and health status of hives. Hives that consumed postbiotic products enhanced their strength, increased bee population and egg laying of the queen, and maintained their reserves of pollen, whereas these parameters decreased in hives belonging to other groups. Furthermore, although the results suggested a favorable effect of postbiotic products on the trend of N. ceranae infection levels, probiotics showed intermediate results. While awaiting long-term results regarding V. destructor infestation, which showed similar trends in all groups, feed supplementation with postbiotics could be an important tool for beekeepers to enhance the strength and health status of their hives.

Olive Polyphenol Oxidase Gene Family.

The phenolic compounds containing hydroxytyrosol are the minor components of virgin olive oil (VOO) with the greatest impact on its functional properties and health benefits. Olive breeding for improving the phenolic composition of VOO is strongly dependent on the identification of the key genes determining the biosynthesis of these compounds in the olive fruit and also their transformation during the oil extraction process. In this work, olive polyphenol oxidase (PPO) genes have been identified and fully characterized in order to evaluate their specific role in the metabolism of hydroxytyrosol-derived compounds by combining gene expression analysis and metabolomics data. Four PPO genes have been identified, synthesized, cloned and expressed in Escherichia coli, and the functional identity of the recombinant proteins has been verified using olive phenolic substrates. Among the characterized genes, two stand out: (i) OePPO2 with its diphenolase activity, which is very active in the oxidative degradation of phenols during oil extraction and also seems to be highly involved in the natural defense mechanism in response to biotic stress, and (ii) OePPO3, which codes for a tyrosinase protein, having diphenolase but also monophenolase activity, which catalyzes the hydroxylation of tyrosol to form hydroxytyrosol.

ß Boswellic Acid Blocks Articular Innate Immune Responses: An In Silico and In Vitro Approach to Traditional Medicine.

Osteoarthritis (OA) is hallmarked as a silent progressive rheumatic disease of the whole joint. The accumulation of inflammatory and catabolic factors such as IL6, TNFα, and COX2 drives the OA pathophysiology into cartilage degradation, synovia inflammation, and bone destruction. There is no clinical available OA treatment. Although traditional ayurvedic medicine has been using Boswellia serrata extracts (BSE) as an antirheumatic treatment for a millennium, none of the BSE components have been clinically approved. Recently, ß boswellic acid (BBA) has been shown to reduce in vivo OA-cartilage loss through an unknown mechanism. We used computational pharmacology, proteomics, transcriptomics, and metabolomics to present solid evidence of BBA therapeutic properties in mouse and primary human OA joint cells. Specifically, BBA binds to the innate immune receptor Toll-like Receptor 4 (TLR4) complex and inhibits both TLR4 and Interleukin 1 Receptor (IL1R) signaling in OA chondrocytes, osteoblasts, and synoviocytes. Moreover, BBA inhibition of TLR4/IL1R downregulated reactive oxygen species (ROS) synthesis and MAPK p38/NFκB, NLRP3, IFNαß, TNF, and ECM-related pathways. Altogether, we present a solid bulk of evidence that BBA blocks OA innate immune responses and could be transferred into the clinic as an alimentary supplement or as a therapeutic tool after clinical trial evaluations.

Benefits of animal-Assisted interventions in preschool children: A systematic review.

Animal-assisted interventions are frequently used to stimulate and improve different skills in children with and without disabilities. However, the heterogeneity of AAI studies in preschool children is large, including different health conditions, duration, outcomes, study design or therapy animals. Therefore, the current study aims to summarize all intervention procedures and provide an updated analysis of the effectiveness of AAI intervention in the early childhood. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA), a systematic search was conducted in two databases: Pubmed (MedLine) and Web of Science. The risk of bias was assessed using the Evidence Project risk of bias tool. A total of 319 articles were identified and 17 were finally included in the qualitative synthesis. Due to the large heterogeneity in terms of study design, intervention, and sample characteristics, it was not possible to conduct a meta-analysis. Animal-assisted interventions might lead to a positive impact on physical, physiological, psychosocial, and language skills in preschool children. These enhancements may be observed both in healthy children and in those with different health conditions, such as intellectual disabilities, cerebral palsy, autism disorder, or Down syndrome. Results must be interpreted with caution due to the large heterogeneity and risk of bias in the included articles.

Evaluation of Genotoxic Effect and Antigenotoxic Potential against DNA Damage of the Aqueous and Ethanolic Leaf Extracts of Annona muricata Using an In Vivo Erythrocyte Rodent Micronucleus Assay.

Annona muricata have been extensively used in traditional medicine to treat multiple diseases, including cancers. This study evaluated the genotoxic potential and antigenotoxic activities of A. muricata aqueous and ethanolic leaf extracts by employing an in vivo erythrocyte rodent micronucleus assay. Different doses (187.5, 375, and 750 mg/kg) of both extracts were administered orally for 5 days alone and combined with cyclophosphamide (CP, 60 mg/kg) to BALB/c mice. Also, it was administered orally to Wistar rats for 5 days through the final stage of gestation. No genotoxic or cytotoxic effects were observed in the two adult rodent models when A. muricata was administered orally nor in newborn rats transplacentally exposed to the extracts. Moreover, A. muricata aqueous and ethanolic leaf extracts demonstrated a protective effect against CP-induced DNA damage. Due to its lack of genotoxic effect and its capacity to decrease DNA damage, A. muricata is likely to open an interest field regarding its potential safe use in clinical applications.

Effect of Music Therapy as a Non-Pharmacological Measure Applied to Alzheimer's Disease Patients: A Systematic Review.

The objective of this research was to learn about the effects of music as a non-pharmacological therapeutic intervention applied to Alzheimer's disease. To this aim, we evaluated its results regarding symptomatology and caregiver burden. Methods: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. We searched Pubmed/Medline (NLM), Web of Science, Scopus, Cochrane and Google Scholar, including articles from 1 January 2011-20 July 2021, using the keywords "Alzheimer´s disease", "Music therapy", "Caregivers overload", "Amnesia retrograde" and "Clinical evolution". To select the articles our criteria included complete text availability, quantitative research of an experimental nature and studies which, at least, figured in SJR or in JCR. Results: We found a relationship between the application of music therapy in patients with Alzheimer's disease and an improvement regarding symptomatology, as it smoothed down the progress of the disease. Using music therapy in Alzheimer's patients also led to a decrease in caregivers' burden and an increase in their well-being. Conclusions: Our results showed the benefits of music therapy, as it improved both patients' symptomatology and caregivers' burden.

Thymus vulgaris essential oil + tobramycin within nanostructured archaeolipid carriers: A new approach against Pseudomonas aeruginosa biofilms.

BACKGROUND: Pseudomonas aeruginosa biofilms in the respiratory tract of patients with an excessive inflammatory context are difficult to eradicate. New medicines that simultaneously target biofilms and inflammation should be developed. HYPOTHESIS: Co-delivery of Thymus vulgaris essential oil (EOT) and tobramycin (TB) by nanostructured archaeolipids carriers (NAC) could support nebulization as well as improve EOT and TB antioxidant, anti-inflammatory and antibiofilm activity. METHODS: NAC(EOT+TB) were prepared by loading EOT and TB in NAC having a compritol and miglyol core, covered with a shell of archaeolipids, extracted from the hyperhalophylic archaebacteria Halorubrum tebenquichense, and Tween 80. NAC(EOT+TB) were structurally characterized, including DSC thermograms, Raman spectra, TB release profile, EOT volatilization and in vitro antioxidant activity. In addition, stability upon nebulization, autoclaving and storage were assessed. The antibiofilm activity on P. aeruginosa PAO1 established biofilm of NAC(EOT+TB) and the cytotoxicity on human lung epithelial cells and macrophage were determined, as well as intracellular reactive oxygen species (ROS) production and cytokines release on LPS stimulated cells. RESULTS: NAC(EOT+TB) showed a size of 197 ± 16 nm with PdI of 0.3 ± 0.1 and ζ Potential of -38 ± 3 mV. Structural characterization suggested that EOT was trapped in the compritol-miglyol core and TB was distributed between the surface of nanoparticles and free in solution. NAC(EOT+TB) displayed a dual release profile of TB, a delayed release of EOT and improved EOTs in vitro antioxidant activity. While NAC(EOT+TB) preserved its structural features after nebulization, autoclaving and 18 months of storage, carriers without archaeolipids gelled at room temperature and showed a significant increase of size after the same storage time. Below cytotoxic concentration, NAC(EOT+TB) decreased bacteria viability and enhanced the disruption of established PAO1 biofilms compared to free TB and EOT. Also, the strong entrapment of EOT in NAC(EOT+TB) delayed its volatilization, decreased intracellular ROS production and maintained its anti-inflammatory activity in LPS stimulated cells. CONCLUSION: Combination of EOT + TB within NAC(EOT+TB) result in a stable and nebulizable formulation that enhanced the antioxidant and anti-biofilm activity of free ingredients, improved their ability to decrease intracellular ROS and provided anti-inflammatory activity, at non-cytotoxic concentrations on eukaryotic cells.

GC/MS Analysis, Antioxidant Activity, and Antimicrobial Effect of Pelargonium peltatum (Geraniaceae).

In recent years, the increase in antibiotic resistance demands searching for new compounds with antimicrobial activity. Phytochemicals found in plants offer an alternative to this problem. The genus Pelargonium contains several species; some have commercial use in traditional medicine such as P. sinoides, and others such as P. peltatum are little studied but have promising potential for various applications such as phytopharmaceuticals. In this work, we characterized the freeze-dried extracts (FDEs) of five tissues (root, stem, leaf, and two types of flowers) and the ethyl acetate fractions from leaf (Lf-EtOAc) and flower (Fwr-EtOAc) of P. peltatum through the analysis by thin-layer chromatography (T.L.C.), gas chromatography coupled to mass spectrometry (GC-MS), phytochemicals quantification, antioxidant capacity, and antimicrobial activity. After the first round of analysis, it was observed that the FDE-Leaf and FDE-Flower showed higher antioxidant and antimicrobial activities compared to the other FDEs, for which FDE-Leaf and FDE-Flower were fractionated and analyzed in a second round. The antioxidant activity determined by ABTS showed that Lf-EtOAc and Fwr-EtOAc had the lowest IC50 values with 27.15 ± 1.04 and 28.11 ± 1.3 µg/mL, respectively. The content of total polyphenols was 264.57 ± 7.73 for Lf-EtOAc and 105.39 ± 4.04 mg G.A./g FDE for Fwr-EtOAc. Regarding the content of flavonoid, Lf-EtOAc and Fw-EtOAc had the highest concentration with 34.4 ± 1.06 and 29.45 ± 1.09 mg Q.E./g FDE. In addition, the minimum inhibitory concentration (M.I.C.) of antimicrobial activity was evaluated: Lf-EtOAc and Fwr-EtOAc were effective at 31.2 µg/mL for Staphylococcus aureus and 62.5 µg/mL for Salmonella enterica, while for the Enterococcus feacalis strain, Fwr-EtOAc presented 31.2 µg/mL of M.I.C. According to the GC-MS analysis, the main compounds were 1,2,3-Benzenetriol (Pyrogallol), with 77.38% of relative abundance in the Lf-EtOAc and 71.24% in the Fwr-EtOAc, followed by ethyl gallate (13.10%) in the Fwr-EtOAc and (Z)-9-Octadecenamide (13.63% and 6.75%) in both Lf-EtOAc and Fwr-EtOAc, respectively.

Benefits of Equine-Assisted Therapies in People with Multiple Sclerosis: A Systematic Review.

This systematic review aimed to provide an up-to-date analysis of the effects of equine-assisted therapies (EAT) in people with multiple sclerosis (PwMS). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed to conduct this systematic review. PubMed and Web of Science databases were employed in the search, which ended in February 2022. The risk of bias analysis was performed using the Evidence Project tool. After removing duplicates, thirty-nine studies were identified. However, only ten fulfilled the inclusion criteria and were included in this systematic review. Therefore, a total of 195 PwMS, aged between 40.3 and 51.3, were included in this systematic review. EAT-based interventions had a mean length of 13.6 weeks with a session´s frequency ranging from ten to once a week. All sessions involved real horses and lasted a mean of 34.4 min. Among the included articles, four were randomized controlled trials (RCT), four did not perform randomization, and two employed a prepost design without a control group. RCTs showed positive effects on quality of life, fatigue, balance, spasticity, and gait speed. Furthermore, non-RCT showed improvements in balance, spasticity, and postural control (postural control was not assessed in RCT studies). Importantly, significant effects were only observed when the comparison group was inactive or followed usual care. Therefore, EAT is a promising and effective therapy to improve quality of life, fatigue, balance, spasticity, and gait speed in PwMS. However, since comparison groups are heterogeneous, results could vary depending on the research design. Moreover, the inclusion of noncontrolled studies (in order to have a wide perspective of the state of art) could increase the risk of bias and make the results be taken with caution.

A novel passive sampling and sequential extraction approach to investigate desorption kinetics of emerging organic contaminants at the sediment-water interface.

Forms of organic contaminants is an important driver of bioavailable fraction and desorption kinetics of pollutants binding to sediments. To determine fluxes and resupply of nine environmentally-relevant antipsychotic drugs, which are emerging pollutants that can have adverse effects on aquatic organisms, interface passive samplers of diffusive gradients in thin films (DGT) were deployed for 21 days, in situ at the sediment-water interface in submerged sandy riverbank sediments. At each deployment time, samples of sediment were collected and subjected to consecutive extraction of pore water, as well as rapidly-desorbing (labile), stable-desorbing, and bound residue fractions. Concentrations of antipsychotic drugs decreased with sediment depth with the greatest concentrations observed in the top 2 cm. Positive fluxes of antipsychotic drugs were observed from sediment to surface water. The dynamic fraction transfer model indicated that the labile fraction can be resupplied with a lag time (> 21 d). When results were further interpreted using the DGT-induced fluxes in soils and sediments (DIFS) model, partial resupply of antipsychotic drugs from sediment particles to porewater was demonstrated. Desorption occurred within the entirety of the observed 15 cm depth of sediment. Fastest rates of resupply were found for carbamazepine and lamotrigine. Size of the labile pool estimated by the DIFS model did not fully explain the observed resupply, while a first-order three-compartment kinetic model for the fast-desorbing fraction can be used to supplement DIFS predictions with estimations of labile pool size.

Cannabis-like activity of Zornia latifolia Sm. detected in vitro on rat cortical neurons: major role of the flavone syzalterin.

Zornia latifolia is a plant suspected to possess psychoactive properties and marketed as a marijuana substitute under the name 'maconha brava'. In this study, the effects of fractions obtained from a 2-propanol extract of aerial portions of the plant were determined by multielectrode array (MEA) analyses on cultured networks of rat cortical neurons. Lipophilic (ZL_lipo, mainly containing flavonoid aglycones), and hydrophilic (ZL_hydro, mainly containing flavonoid glycosides) fractions were initially obtained from the raw extract. ZL_lipo significantly inhibited mean firing rate (MFR) and mean bursting rate (MBR) of MEA recordings, while ZL_hydro induced no inhibition. Column chromatography separation of ZL_lipo yielded five fractions (ZL1-ZL5), among which ZL1 induced the strongest MFR and MBR inhibition. NMR and HPLC-MS analyses of ZL1 revealed the prevalence of the common flavonoids genistein (1) and apigenin (2) (in about a 1:1 ratio), and the presence of the rare flavone syzalterin (6,8-dimethylapigenin) (3) as a minor compound. Exposures of MEA to apigenin and genistein standards did not induce the MFR and MBR inhibition observed with ZL1, whereas exposure to syzalterin standard or to a 1:9 mixture syzalterin-genistein induced effects similar to ZL1. These inhibitory effects were comparable to that observed with high-THC hashish, possibly accounting for the plant psychoactive properties. Data indicate that Z. latifolia, currently marketed as a free herbal product, should be subjected to measures of control. In addition, syzalterin showed distinctive pharmacological properties, opening the way to its possible exploitation as a neuroactive drug.

Spiritual Care in Advanced Dementia from the Perspective of Health Providers: A Qualitative Systematic Review.

BACKGROUND: Worldwide, 47 million people suffer from dementia. Despite recognizing the importance of spirituality within dementia care, it is still unclear how this should be integrated into dementia services. AIM: To explore the perspective of health professionals regarding the spiritual care of people with advanced dementia. METHODS: A qualitative systematic review was performed following the Enhancing Transparency in Reporting the Synthesis of Qualitative Research guidelines for the study design. The inclusion criteria included original articles published from January 2008 to March 2019, using either qualitative or mixed methods. The quality of the articles included was evaluated using the consolidated criteria for reporting qualitative research, Standards for Reporting Qualitative Research, and the Critical Appraisal Skills Programme. Synthesis of findings was performed using thematic analysis. RESULTS: Twelve studies were included in the review. Seventeen categories were identified, grouped into four themes: (1) the perception of spirituality, including the failure to address the same, (2) the spiritual needs of people with advanced dementia, (3) spiritual needs from health care providers, and (4) addressing spirituality, with the following categories: music, significant activities, among others. CONCLUSIONS: Spirituality is not formally addressed in this population, and professionals do not feel confident enough to be able to integrate spirituality in their care. It is necessary to identify and record the spiritual needs of people with advanced dementia, as well as to design specific care programs.

Impact of Genetic Polymorphism on Response to Therapy in Non-Alcoholic Fatty Liver Disease.

In the last decades, the global prevalence of non-alcoholic fatty liver disease (NAFLD) has reached pandemic proportions with derived major health and socioeconomic consequences; this tendency is expected to be further aggravated in the coming years. Obesity, insulin resistance/type 2 diabetes mellitus, sedentary lifestyle, increased caloric intake and genetic predisposition constitute the main risk factors associated with the development and progression of the disease. Importantly, the interaction between the inherited genetic background and some unhealthy dietary patterns has been postulated to have an essential role in the pathogenesis of NAFLD. Weight loss through lifestyle modifications is considered the cornerstone of the treatment for NAFLD and the inter-individual variability in the response to some dietary approaches may be conditioned by the presence of different single nucleotide polymorphisms. In this review, we summarize the current evidence on the influence of the association between genetic susceptibility and dietary habits in NAFLD pathophysiology, as well as the role of gene polymorphism in the response to lifestyle interventions and the potential interaction between nutritional genomics and other emerging therapies for NAFLD, such as bariatric surgery and several pharmacologic agents.

Cytotoxic and Genotoxic Evaluation of the Aqueous and Hydroalcoholic Leaf and Bark Extracts of Crataegus oxyacantha in Murine Model.

Crataegus oxyacantha has been mainly used in traditional medicine for the treatment of cardiovascular diseases. However, its safety profile has not been fully established, since only the genotoxic effects of C. oxyacantha fruit have been described. Therefore, the objective of this work was evaluating the cytotoxicity and genotoxicity of the aqueous and hydroalcoholic leaf and bark extracts of C. oxyacantha by means of the micronucleus test in a murine model. Doses of 2000, 1000, and 500 mg/kg of both extracts were administered orally for 5 days in mice of the Balb-C strain. Peripheral blood smears were performed at 0, 24, 48, 72, and 96 h after each administration. The number of polychromatic erythrocytes (PCEs), micronucleated polychromatic erythrocytes (MNPCEs), and micronucleated erythrocytes (MNEs) was determined at the different sampling times. Our results showed that the leaf and bark of C. oxyacantha increase the number of MNEs at the 2000 mg/kg dose, and only the aqueous leaf extract decreases the number of PCEs at the same dose. Therefore, the aqueous and hydroalcoholic leaf and bark extracts of C. oxyacantha showed genotoxic effects, and only the aqueous leaf extract exhibited cytotoxic effects.

Multi-Tissue Transcriptomic-Informed In Silico Investigation of Drugs for the Treatment of Dengue Fever Disease.

Transcriptomics, proteomics and pathogen-host interactomics data are being explored for the in silico-informed selection of drugs, prior to their functional evaluation. The effectiveness of this kind of strategy has been put to the test in the current COVID-19 pandemic, and it has been paying off, leading to a few drugs being rapidly repurposed as treatment against SARS-CoV-2 infection. Several neglected tropical diseases, for which treatment remains unavailable, would benefit from informed in silico investigations of drugs, as performed in this work for Dengue fever disease. We analyzed transcriptomic data in the key tissues of liver, spleen and blood profiles and verified that despite transcriptomic differences due to tissue specialization, the common mechanisms of action, "Adrenergic receptor antagonist", "ATPase inhibitor", "NF-kB pathway inhibitor" and "Serotonin receptor antagonist", were identified as druggable (e.g., oxprenolol, digoxin, auranofin and palonosetron, respectively) to oppose the effects of severe Dengue infection in these tissues. These are good candidates for future functional evaluation and clinical trials.

The Phylogeography of Potato Virus X Shows the Fingerprints of Its Human Vector.

Potato virus X (PVX) occurs worldwide and causes an important potato disease. Complete PVX genomes were obtained from 326 new isolates from Peru, which is within the potato crop's main domestication center, 10 from historical PVX isolates from the Andes (Bolivia, Peru) or Europe (UK), and three from Africa (Burundi). Concatenated open reading frames (ORFs) from these genomes plus 49 published genomic sequences were analyzed. Only 18 of them were recombinants, 17 of them Peruvian. A phylogeny of the non-recombinant sequences found two major (I, II) and five minor (I-1, I-2, II-1, II-2, II-3) phylogroups, which included 12 statistically supported clusters. Analysis of 488 coat protein (CP) gene sequences, including 128 published previously, gave a completely congruent phylogeny. Among the minor phylogroups, I-2 and II-3 only contained Andean isolates, I-1 and II-2 were of both Andean and other isolates, but all of the three II-1 isolates were European. I-1, I-2, II-1 and II-2 all contained biologically typed isolates. Population genetic and dating analyses indicated that PVX emerged after potato's domestication 9000 years ago and was transported to Europe after the 15th century. Major clusters A-D probably resulted from expansions that occurred soon after the potato late-blight pandemic of the mid-19th century. Genetic comparisons of the PVX populations of different Peruvian Departments found similarities between those linked by local transport of seed potato tubers for summer rain-watered highland crops, and those linked to winter-irrigated crops in nearby coastal Departments. Comparisons also showed that, although the Andean PVX population was diverse and evolving neutrally, its spread to Europe and then elsewhere involved population expansion. PVX forms a basal Potexvirus genus lineage but its immediate progenitor is unknown. Establishing whether PVX's entirely Andean phylogroups I-2 and II-3 and its Andean recombinants threaten potato production elsewhere requires future biological studies.

Anti-platelet activity and chemical characterization by UPLC-DAD-ESI-QTOF-MS of the main polyphenols in extracts from Psidium leaves and fruits.

In Costa Rica, two species of Psidium fruits, P. guajava and P. friedrichsthalianum, are widely consumed as food and used in folk medicine. Although studies have revealed the health effects of these fruits, there has been little research showing the antiplatelet activity of these species. This work evaluated the antiplatelet potential of aqueous extracts made from leaves and fruits of pink guava and Costa Rican guava. Platelet aggregation was induced by the platelet agonists ADP, TRAP-6, collagen and PMA. Platelet activation and secretion were studied using flow cytometry. The chemical profiles of the four extracts were characterized using UPLC-DAD-ESI-QTOF-MS. The studies revealed that the aqueous extracts of leaves and fruits of P. guajava and P. friedrichsthalianum inhibited platelet aggregation induced by ADP (4 µM), TRAP-6 (5 µM), collagen (1 µg mL-1) and PMA (100 nM), and the effect was dependent on the extract concentration. Extracts of leaves and fruits of pink guava and Costa Rican guava reduced secretion of P-selectin and activation of GP IIb/IIIa. The extracts of leaves and fruits of pink guava and Costa Rican guava proved to be a rich source of phenolic compounds, mainly quercetin aglycones and proanthocyanidins derived from (epi) catechin units. Other compounds such as ellagitannins, and benzophenones were also putatively identified. This research showed that P. guajava and P. friedrichsthalianum could potentially be used for the prevention of thrombotic events.

Can We Treat Neuroinflammation in Alzheimer's Disease?

Alzheimer's disease (AD), considered the most common type of dementia, is characterized by a progressive loss of memory, visuospatial, language and complex cognitive abilities. In addition, patients often show comorbid depression and aggressiveness. Aging is the major factor contributing to AD; however, the initial cause that triggers the disease is yet unknown. Scientific evidence demonstrates that AD, especially the late onset of AD, is not the result of a single event, but rather it appears because of a combination of risk elements with the lack of protective ones. A major risk factor underlying the disease is neuroinflammation, which can be activated by different situations, including chronic pathogenic infections, prolonged stress and metabolic syndrome. Consequently, many therapeutic strategies against AD have been designed to reduce neuro-inflammation, with very promising results improving cognitive function in preclinical models of the disease. The literature is massive; thus, in this review we will revise the translational evidence of these early strategies focusing in anti-diabetic and anti-inflammatory molecules and discuss their therapeutic application in humans. Furthermore, we review the preclinical and clinical data of nutraceutical application against AD symptoms. Finally, we introduce new players underlying neuroinflammation in AD: the activity of the endocannabinoid system and the intestinal microbiota as neuroprotectors. This review highlights the importance of a broad multimodal approach to treat successfully the neuroinflammation underlying AD.