Zuccagnia punctata Cav., a Potential Environmentally Friendly and Sustainable Bionematicide for the Control of Argentinean Horticultural Crops.

This research was designed to investigate the metabolite profiling, phenolics, and flavonoids content as well as the potential nematicidal properties of decoction (ZpDe), orange-yellow resin (ZpRe) and essential oil (ZpEO) from Argentinean medicinal plant Zuccagnia punctata Cav. Additionally, the antioxidant and antibacterial properties of ZpDe and ZpEO were determined. Metabolite profiling was obtained by an ultrahigh-resolution liquid chromatography MS analysis (UHPLC-ESI-QTOF/OT-MS-MS) and GCMS. The nematicidal activity was assayed by a standardized method against Meloidogyne incognita. The antioxidant properties were screened by four methods: (2,2-diphenyl-1-picrylhydrazyl assay (DPPH), Trolox equivalent antioxidant activity assay (TEAC), ferric-reducing antioxidant power assay (FRAP), and lipid peroxidation in erythrocytes (ILP). The antibacterial activity was evaluated according to the Clinical and Laboratory Standards Institute (CLSI) rules. The ZpDe, ZpRe and ZpEO displayed a strong nematicidal activity with an LC50 of 0.208, 0.017 and 0.142 mg/mL, respectively. On the other hand, the ZpDe showed a strong DPPH scavenging activity (IC50 = 28.54 µg/mL); ILP of 87.75% at 250 µg ZpDe/mL and moderated antimicrobial activity. The ZpEO showed promising activity against a panel of yeasts Candida albicans and non-albicans (ATCC and clinically isolated) with MIC values from 750 to 1500 µg/mL. The ZpDe showed a content of phenolics and flavonoid compounds of 241 mg GAE/g and 10 mg EQ/g, respectively. Fifty phenolic compounds were identified in ZpDe by ultrahigh-resolution liquid chromatography (UHPLC-PDA- Q-TOF-MS) analysis, while forty-six phenolic compounds were identified in ZpRe by UHPLC-ESI-Q-OT-MS-MS and twenty-nine in ZpEO using a GC-MS analysis, updating the knowledge on the chemical profile of this species. The results support and standardize this medicinal plant mainly as a potential environmentally friendly and sustainable bionematicide for the control of Argentinean horticultural crops including tomatoes and peppers and as a source of antimicrobial and antioxidant compounds which could be further explored and exploited for potential applications.

UHPLC-MS Phenolic Fingerprinting, Aorta Endothelium Relaxation Effect, Antioxidant, and Enzyme Inhibition Activities of Azara dentata Ruiz & Pav Berries.

Azara dentata Ruiz & Pav. is a small Chilean native plant from Patagonia, a producer of small white reddish berries. For the first time, the proximal analysis of the fruits, phenolic fingerprinting, the antioxidant activity, and the enzymatic inhibition and relaxation effects in rat aorta induced by the ethanolic extract of these fruits were investigated. The proximal composition and the mineral (Ca: 2434 ± 40 mg/kg; Mg: 702 ± 13 mg/kg; Fe: 117.1 ± 1.6 mg/kg; Zn: 16.1 ± 0.4 mg/kg) and heavy metal (As: 121 ± 11 µg/kg; Cd: 152 ± 5 µg/kg; Hg: 7.7 ± 1.3 µg/kg; Pb 294 ± 4 µg/kg) contents were analyzed. Anthocyanins, flavonoids, phenolic acids, and coumarins were identified using UHPLC-PDA-QTOF-MS. The ethanolic extracts showed a total phenolic content of 23.50 ± 0.93 mg GAE/g extract. In addition, the antioxidant activity was assessed using both DPPH and TEAC (28.64 ± 1.87 and 34.72 ± 2.33 mg Trolox/g of dry fruit, respectively), FRAP (25.32 ± 0.23 mg Trolox equivalent/g dry fruit), and ORAC (64.95 ± 1.23 mg Trolox equivalents/g dry fruit). The inhibition of enzymatic activities (acetylcholinesterase IC50: 2.87 + 0.23 µg extract/mL, butyrylcholinesterase IC50: 6.73 + 0.07 µg extract/mL, amylase IC50: 5.6 ± 0.0 µg extract/mL, lipase IC50: 30.8 ± 0.0 µg extract/mL, and tyrosinase IC50: 9.25 ± 0.15 µg extract/mL) was also assessed. The extract showed 50-60% relaxation in rat aorta (intact), mediated thorough the release of endothelial nitric oxide. Our results suggest that A. dentata is a good source of compounds with the capacity to inhibit important enzymes, can be hypotensive, and can thus have good potentiality as supplements in the amelioration of neurodegenerative diseases and could also have potential to be used to develop new functional foods. The study highlights the benefits of these neglected small fruits and could boost their consumption.

Rendimiento de los índices predictores de gravedad en pacientes adultos hospitalizados por neumonía adquirida en la comunidad por coronavirus SARS-CoV-2 / Performance of severity indexes for the prediction of adverse events among patients hospitalized for SARS-CoV-2

BACKGROUND: Severity assessment in adult patients with community-acquired pneumonia (CAP) allows to guide the site of care (ambulatory or hospitalization), diagnostic workup and treatment. AIM: To examine the performance of twelve severity predictive indexes (CRB65, CURB65, PSI, SCAP, SMART-COP, REA-ICU, ATS minor criteria, qSOFA, CALL, COVID GRAM, 4C, STSS) in adult patients hospitalized for CAP associated with SARS-CoV-2. MATERIAL AND METHODS: Prospective clinical study conducted between April 1 and September 30, 2020 in adult patients hospitalized for CAP associated with COVID-19 in a clinical hospital. The recorded adverse events were admission to the critical care unit, use of mechanical ventilation (MV), prolonged length of stay, and hospital mortality. The predictive rules were compared based on their sensitivity, specificity, predictive values, and area under the receiver operator characteristic (ROC) curve. RESULTS: Adverse events were more common and hospital stay longer in the high-risk categories of the different prognostic indices. CURB-65, PSI, SCAP, COVID GRAM, 4 C and STSS predicted the risk of death accurately. PSI, SCAP, ATS minor criteria, CALL and 4 C criteria were sensitive in predicting the risk of hospital mortality with high negative predictive value. The performance of different prognostic indices decreased significantly for the prediction of ICU admission, use of mechanical ventilation, and prolonged hospital length of stay. CONCLUSIONS: The performance of the prognostic indices differs significantly for the prediction of adverse events in immunocompetent adult patients hospitalized for community-acquired pneumonia associated with COVID-19.

Ultra-High-Resolution Liquid Chromatography Coupled with Electrospray Ionization Quadrupole Time-of-Flight Mass Spectrometry Analysis of Tessaria absinthioides (Hook. & Arn.) DC. (Asteraceae) and Antioxidant and Hypocholesterolemic Properties.

Recently, we reported the chemical profile and the hypocholesterolemic effects of a decoction of Tessaria absinthioides (Hook. & Arn.) DC. (Asteraceae). In this study, we evaluated a methanolic extract (METa) instead. Metabolite profiling was conducted using ultra-high-resolution liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-ESI-QTOF-MS), identifying thirty compounds, including flavonoids, phenolic acids, fatty acids, and phorbolesters. Antioxidant properties were assessed through 2,2-diphenyl-1-picrylhydrazyl (DPPH), Trolox equivalent antioxidant activity (TEAC), ferric-reducing antioxidant power (FRAP), and inhibition of lipid peroxidation in erythrocytes (ILP) assays, exhibiting robust antioxidant activity. The in vivo impact of METa on serum lipid parameters and liver X receptors (LXRs) was evaluated in a hypercholesterolemic animal model. After 14 days on a high-fat diet, male rats received either a vehicle (V) or METa100, METa200 or METa500 (100; 200 and 500 mg METa/kg animal, respectively) for an additional two weeks. METa500 reduced total cholesterol levels (17.62%; p < 0.05) and all doses increased high-density lipoprotein cholesterol levels (METa100: 86.27%; METa200: 48.37%, and METa500: 29.42%; p < 0.0001). However, METa did not alter LXRs expression. The observed antioxidant and hypocholesterolemic properties of METa may be linked to the presence of six di-caffeoylquinic acids. These findings underscore T. absinthioides as a potential candidate for the treatment of metabolic disease.

[Performance of severity indexes for the prediction of adverse events among patients hospitalized for SARS-CoV-2]. / Rendimiento de los índices predictores de gravedad en pacientes adultos hospitalizados por neumonía adquirida en la comunidad por coronavirus SARS-CoV-2.

BACKGROUND: Severity assessment in adult patients with community-acquired pneumonia (CAP) allows to guide the site of care (ambulatory or hospitalization), diagnostic workup and treatment. AIM: To examine the performance of twelve severity predictive indexes (CRB65, CURB65, PSI, SCAP, SMART-COP, REA-ICU, ATS minor criteria, qSOFA, CALL, COVID GRAM, 4C, STSS) in adult patients hospitalized for CAP associated with SARS-CoV-2. MATERIAL AND METHODS: Prospective clinical study conducted between April 1 and September 30, 2020 in adult patients hospitalized for CAP associated with COVID-19 in a clinical hospital. The recorded adverse events were admission to the critical care unit, use of mechanical ventilation (MV), prolonged length of stay, and hospital mortality. The predictive rules were compared based on their sensitivity, specificity, predictive values, and area under the receiver operator characteristic (ROC) curve. RESULTS: Adverse events were more common and hospital stay longer in the high-risk categories of the different prognostic indices. CURB-65, PSI, SCAP, COVID GRAM, 4 C and STSS predicted the risk of death accurately. PSI, SCAP, ATS minor criteria, CALL and 4 C criteria were sensitive in predicting the risk of hospital mortality with high negative predictive value. The performance of different prognostic indices decreased significantly for the prediction of ICU admission, use of mechanical ventilation, and prolonged hospital length of stay. CONCLUSIONS: The performance of the prognostic indices differs significantly for the prediction of adverse events in immunocompetent adult patients hospitalized for community-acquired pneumonia associated with COVID-19.

IL-15 blockade and rapamycin rescue multifactorial loss of factor VIII from AAV-transduced hepatocytes in hemophilia A mice.

Hepatic adeno-associated viral (AAV) gene transfer has the potential to cure the X-linked bleeding disorder hemophilia A. However, declining therapeutic coagulation factor VIII (FVIII) expression has plagued clinical trials. To assess the mechanistic underpinnings of this loss of FVIII expression, we developed a hemophilia A mouse model that shares key features observed in clinical trials. Following liver-directed AAV8 gene transfer in the presence of rapamycin, initial FVIII protein expression declines over time in the absence of antibody formation. Surprisingly, loss of FVIII protein production occurs despite persistence of transgene and mRNA, suggesting a translational shutdown rather than a loss of transduced hepatocytes. Some of the animals develop ER stress, which may be linked to hepatic inflammatory cytokine expression. FVIII protein expression is preserved by interleukin-15/interleukin-15 receptor blockade, which suppresses CD8+ T and natural killer cell responses. Interestingly, mice with initial FVIII levels >100% of normal had diminishing expression while still under immune suppression. Taken together, our findings of interanimal variability of the response, and the ability of the immune system to shut down transgene expression without utilizing cytolytic or antibody-mediated mechanisms, illustrate the challenges associated with FVIII gene transfer. Our protocols based upon cytokine blockade should help to maintain efficient FVIII expression.

Synthesis of Iron, Zinc, and Manganese Nanofertilizers, Using Andean Blueberry Extract, and Their Effect in the Growth of Cabbage and Lupin Plants.

The predominant aim of the current study was to synthesize the nanofertilizer nanoparticles ZnO_MnO-NPs and FeO_ZnO-NPs using Andean blueberry extract and determine the effect of NPs in the growth promotion of cabbage (Brassica oleracea var. capitata) and Andean lupin (Lupinus mutabilis sweet) crops. The nanoparticles were analyzed by visible spectrophotometry, size distribution (DLS), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Solutions of nanoparticle concentrations were applied to cabbage, with solutions of 270 and 540 ppm of ZnO_MnO-NPs and 270 and 540 ppm of FeO_ZnO-NPs applied to Andean lupin. Zinc was used in both plants to take advantage of its beneficial properties for plant growth. Foliar NPs sprays were applied at the phenological stage of vegetative growth of the cabbage or Andean lupin plants grown under greenhouse conditions. The diameter of the NPs was 9.5 nm for ZnO, 7.8 nm for FeO, and 10.5 nm for MnO, which facilitate the adsorption of NPs by the stomata of plants. In Andean lupin, treatment with 270 ppm of iron and zinc indicated increases of 6% in height, 19% in root size, 3.5% in chlorophyll content index, and 300% in leaf area, while treatment with 540 ppm of iron and zinc yielded no apparent increases in any variable. In cabbage, the ZnO_MnO-NPs indicate, at a concentration of 270 ppm, increases of 10.3% in root size, 55.1% in dry biomass, 7.1% in chlorophyll content, and 25.6% in leaf area. Cabbage plants treated at a concentration of 540 ppm produced increases of 1.3% in root size and 1.8% in chlorophyll content, compared to the control, which was sprayed with distilled water. Therefore, the spray application of nanofertilizers at 270 ppm indicated an important improvement in both plants' growth.

Anti-Trypanosoma cruzi activity of alkaloids isolated from Habranthus brachyandrus (Amaryllidaceae) from Argentina.

BACKGROUND: Chagas disease, caused by the parasite Trypanosoma cruzi, affects over six million people worldwide, mainly in Latin American countries. Currently available drugs have variable efficacy in the chronic phase and significant side effects, so there is an urgent need for safer chemotherapeutic treatments. Natural products provide privileged structures that could serve as templates for the synthesis of new drugs. Among them, Amaryllidaceae plants have proved to be a potential natural source of therapeutical agents due to their rich diversity in alkaloids. PURPOSE: To identify alkaloids with anti-T. cruzi activity from Habranthus brachyandrus (Baker) Sealy (Amaryllidaceae, subfamily Amaryllidoideae) collected in Argentina. METHODS: An H. brachyandrus alkaloid extract was tested against T. cruzi, and its cytotoxicity profile was evaluated against two mammalian cell lines to ascertain its selectivity against the parasite and potential liver toxicity. It was also assessed by a stage-specific anti-amastigote assay and analysed by GC/MS to determine its alkaloid profile. The isolated alkaloids were also tested using the aforementioned assays. RESULTS: The extract showed high and specific activity against T. cruzi. The alkaloids lycoramine, galanthindole, 8-O-demethylmaritidine, 8-O-demethylhomolycorine, nerinine, trisphaeridine, deoxytazettine, and tazettamide were identified by means of GC-MS. In addition, hippeastidine (also named aulicine), tazzetine, ismine, and 3-epimacronine were isolated. The alkaloid ismine was specifically active against the parasite and had low toxicity against HepG2 cells, but did not show anti-amastigote activity. CONCLUSION: The extract had specific anti-T. cruzi activity and the isolated alkaloid ismine was partially responsible of it. These results encourage further exploration of H. brachyandrus alkaloids in search of novel starting points for Chagas disease drug development.

Tessaria absinthioides (Hook. & Arn.) DC. (Asteraceae) Decoction Improves the Hypercholesterolemia and Alters the Expression of LXRs in Rat Liver and Hypothalamus.

Chronic high-fat diet consumption induces hypercholesterolemia. The effect of Tessaria absinthioides (Hook. & Arn.) DC. (Asteraceae) was studied on the levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), and triglycerides, and on the expression of liver X receptors (LXRs) in a hypercholesterolemic model. Adult male rats received a normal diet (ND) or a high-fat diet (HFD; normal diet + bovine fat + cholesterol). After 14 days, rats received water (W) or a decoction of the aerial parts of T. absinthioides (Ta; 10% w/v) for 2, 4, or 6 weeks. Four and six weeks of Ta improved the levels of TC and HDL-c in HFD. After 6 weeks of Ta, the expression of LXRs in HFD was the same as that in ND in both tissues. The Ta chemical profile was studied with an ultrahigh resolution liquid chromatography Orbitrap MS analysis (UHPLC-PDA-OT-MS/MS). Fifty-one compounds were identified, of which twelve are reported for the first time. Among these compounds, caffeoylquinic acid and its derivatives could modify the lipid profile and the expression of LXRs. This is the first in vivo report of T. absinthioides, which may be a potential candidate against hypercholesterolemia.

Evaluación de los predictores clínicos de infección respiratoria aguda por coronavirus SARS-CoV-2 en población adulta / Clinical features of COVID-19 infection among patients consulting at an emergency service

Background: COVID-19 is a serious public health problem worldwide. Aim: To describe the clinical features of COVID-19 infection in adult patients consulting at an Emergency Service. Material and Methods: Descriptive prospective study of adult patients with suspected COVID-19 consulting between April 1 and July 31, 2020, at the Emergency Service of a clinical hospital. Clinical features, chronic comorbidities and demographic data were recorded. Results: We assessed 2,958 adult patients aged 42 ± 15 years (46% males). In 54% of them, COVID-19 infection was confirmed, 40% had preexisting diseases, especially hypertension (15%), hypothyroidism (6%), diabetes (6%), asthma (5%) and obesity (6%). The main clinical manifestations associated with COVID-19 were general malaise (79%), anorexia (38%), myalgia (64%), fever (52%), headache (70%), anosmia/dysgeusia (60%), cough (56%), dyspnea (54%) and diarrhea (36%). In the multivariate analysis, the main clinical predictors of COVID-19 infection were malaise, anorexia, fever, myalgia, headache, nasal congestion, cough, expectoration, anosmia/dysgeusia, and history of close contact with a SARS-CoV-2 patient. Odynophagia and chest discomfort were negative predictors of the disease. The history of fever associated with anorexia, cough, and dyspnea or anosmia/dysgeusia and close contact with a SARS-CoV-2 patient had high specificity and positive predictive value for COVID-19 infection. Conclusions: Clinical features of COVID-19 infection were highly unspecific in these patients. Clinical diagnostic prediction models could be useful to support healthcare decision making at primary care setting.

Zuccagnia punctata Cav. Essential Oil into Poly(ε-caprolactone) Matrices as a Sustainable and Environmentally Friendly Strategy Biorepellent against Triatoma infestans (Klug) (Hemiptera, Reduviidae).

The main strategies against Triatoma infestans (primary vector responsible for the Chagas disease transmission) are the elimination or reduction of its abundance in homes through the application of insecticides or repellents with residual power, and environmental management through the improvement of housing. The use of plant-derived compounds as a source of therapeutic agents (i.e., essential oils from aromatic plants and their components) is a valuable alternative to conventional insecticides and repellents. Essential oil-based insect repellents are environmentally friendly and provide reliable personal protection against the bites of mosquitoes and other blood-sucking insects. This study investigates, for the first time to our knowledge, the potential repellent activity of Zuccagnia punctata essential oil (ZEO) and poly(ε-caprolactone) matrices loaded with ZEO (ZEOP) prepared by solvent casting. The analysis of its essential oil from aerial parts by GC-FID and GC-MS, MS allowed the identification of 25 constituents representing 99.5% of the composition. The main components of the oil were identified as (-)-5,6-dehydrocamphor (62.4%), alpha-pinene (9.1%), thuja-2, 4 (10)-diene (4.6%) and dihydroeugenol (4.5%). ZEOP matrices were homogeneous and opaque, with thickness of 800 ± 140 µm and encapsulation efficiency values above 98%. ZEO and ZEOP at the lowest dose (0.5% wt./wt., 96 h) showed a repellency of 33 and 73% respectively, while at the highest dose (1% wt./wt., 96 h) exhibited a repellent activity of 40 and 66 %, respectively. On the other hand, until 72 h, ZEO showed a strong repellent activity against T. infestans (88% repellency average; Class V) to both concentrations, compared with positive control N-N diethyl-3-methylbenzamide (DEET). The essential oils from the Andean flora have shown an excellent repellent activity, highlighting the repellent activity of Zuccagnia punctata. The effectiveness of ZEO was extended by its incorporation in polymeric systems and could have a potential home or peridomiciliary use, which might help prevent, or at least reduce, Chagas' disease transmission.

Transmisión del virus del dengue y su relación con factores climáticos durante los períodos intra e interepidémicos en Santo Domingo, República Dominican / Dengue Virus Transmission and its Relationship with Climatic Factors During Intra and Interepidemic Periodsin Santo Domingo, Dominican Republic

Introducción: Aedes spp. y la dinámica del virus del dengue está altamente influenciada por factores ambientales. Una relación detallada entre el clima y la enfermedad en los períodos inter e intra-epidémicos podrían beneficiar la vigilancia del dengue para optimizar la preparación y las políticas adecuadas de control de vectores. Métodos: se analizaron los informes de casos de dengue y las variables climáticas en Santo Domingo, República Dominicana, para determinar la correlación del período 2012- 2018 y los diferentes tiempos de retraso. Se llevó a cabo un análisis de regresión de dichas variables para comprender mejor las relaciones entre las tasas de incidencia del dengue y los cambios climáticos. Resultados: durante los brotes epidémicos, la temperatura (r = 0.73, p <0.001) y la humedad relativa (r = -0.2, p = 0.009) se correlacionan significativamente con la incidencia del dengue con un retraso de 9 semanas, el análisis de regresión muestra que la temperatura media (b = 62.401, p < 0.001), precipitación (b = 2.810, p <0.001) y humedad relativa (b = -5.462, p = 0.025) fueron predictores significativos. Durante los períodos inter-epidémico, la temperatura (r = 0.23, p <0.001) tuvo una correlación significativa con la incidencia del dengue con un retraso de 7 semanas, la humedad relativa (b = 1.454, p <0.05) y la temperatura media (b = 5.14, p <0.01) son predictores significativos de la cantidad de casos de dengue. La precipitación no se correlacionó significativamente con la incidencia del dengue. Conclusiones: existe una relación no lineal entre los factores climáticos y la incidencia del dengue. La infección por dengue depende del clima, y la temperatura parece jugar un papel importante en los factores climáticos.

Introduction: Aedes spp. and Dengue Virus dynamics are highly influenced by environmental factors. A detailed relationship between climate and disease in inter and intra-epidemic periods may benefit dengue surveillance, preparedness, and adequate vector control policies. Methods: Dengue case reports and climatic variables in Santo Domingo, Dominican Republic, were analyzed for climate variables correlation from the period 2012-2018 and varying lag times. Regression analysis of climatic variables was carried out to better understand significant correlations between dengue incidence rates and changes in climate. Results: During epidemic outbreaks, temperature (r = 0.73, p < 0.001) and relative humidity (r = -0.22, p = 0.009) demonstrated a significant correlation with dengue incidence. Our regression analysis demonstrates an increase 62.4 cases for each degree Celsius increased with a 9-week-lag. Regression analysis also demonstrated mean temperature (b= 62.401, p < 0.001), precipitation (b = 2.810, p < 0.001), and relative humidity (b = -5.462, p = 0.025) to be significant predictors. During inter-epidemic periods, temperature (r = 0.23, p < 0.001) had a significant correlation with dengue incidence with a 7-week-lag, which demonstrates that relative humidity (b = 1.454, p < 0.05), and mean temperature (b = 5.14, p < 0.01) are significant predictors of the quantity of dengue cases. Precipitation did not significantly correlate with dengue incidence. Conclusions: A non-linear relationship between climatic factors and dengue incidence exists in the Dominican Republic. Dengue infection is climate-dependent and temperature seems to play a significant role in climatic factors

UHPLC-ESI-OT-MS Phenolics Profiling, Free Radical Scavenging, Antibacterial and Nematicidal Activities of "Yellow-Brown Resins" from Larrea spp.

This research was designed to investigate the metabolite profiling, phenolics and flavonoids content and the potential antioxidant, antibacterial and nematicidal activities of "yellow-brown resins" from Larrea divaricata Cav (LdRe) and L. nitida Cav (LnRe). Metabolite profiling was obtained using an ultrahigh resolution liquid chromatography orbitrap MS analysis (UHPLC-ESI-OT-MS). The antioxidant properties were screened by four methods: 2,2-diphenyl-1-picrylhydrazyl assay (DPPH), trolox equivalent antioxidant activity assay (TEAC), ferric-reducing antioxidant power assay (FRAP) and lipid peroxidation in erythrocytes (LP). The antibacterial activity was evaluated according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. In addition, the potential combinatory effect was analyzed with the fractional inhibitory concentration index (FICI) values using the checkerboard design. The nematicidal activity was carried out according to a standardized protocol. LdRe and LnRe showed a strong capture of the DPPH radical withvalues around 8.4 µg resin/mL; FRAP (1.69-1.94 mgTE/ g resin), TEAC (1.08-1.09 mgTE/g resin) and LP (81-82% at 100 µg of resin/mL) assays. A strong antimicrobial activity was displayed by both resins against methicillin-sensitive Staphylococcus aureus ATCC 25923(MSSA) and methicillin-resistant S. aureus ATCC 43300(MRSA) (MICs = 16-32 µg resin/mL). Additionally, the combination of LdRe or LnRe with the antibiotic cefotaxime showed an indifferent effect (FICI values = 1-1.25), however, this combinationcould be a potential strategy to reduce the drug doses, and in this way can be a potential alternative to reduce bacterial resistance. On the other hand, the resins showed a scarce nematicidal potential toward J2 Meloidogyne incognita; an important nematode infecting horticultural crops. Phenolics compounds were identified by UHPLC-PDA-OT-MS analysis, updating the knowledge on the chemical profile of these species. These results, together with the high content of quantified phenolics and flavonoids, allow the phenolics-enriched resins of these two Larrea species to be considered as a promising sustainable source of compounds of pharmacological interest.

Alkaloids Analysis of Habranthus cardenasianus (Amaryllidaceae), Anti-Cholinesterase Activity and Biomass Production by Propagation Strategies.

Plants in the Amaryllidaceae family synthesize a diversity of bioactive alkaloids. Some of these plant species are not abundant and have a low natural multiplication rate. The aims of this work were the alkaloids analysis of a Habranthus cardenasianus bulbs extract, the evaluation of its inhibitory activity against cholinesterases, and to test several propagation strategies for biomass production. Eleven compounds were characterized by GC-MS in the alkaloid extract, which showed a relatively high proportion of tazettine. The known alkaloids tazettine, haemanthamine, and the epimer mixture haemanthidine/6-epi-haemanthidine were isolated and identified by spectroscopic methods. Inhibitory cholinesterases activity was not detected. Three forms of propagation were performed: bulb propagation from seed, cut-induced bulb division, and micropropagated bulbs. Finally, different imbibition and post-collection times were evaluated in seed germination assays. The best propagation method was cut-induced bulb division with longitudinal cuts into quarters (T1) while the best conditions for seed germination were 0-day of post-collection and two days of imbibition. The alkaloids analyses of the H. cardenasianus bulbs showed that they are a source of anti-tumoral alkaloids, especially pretazettine (tazettine) and T1 is a sustainable strategy for its propagation and domestication to produce bioactive alkaloids.

[Clinical features of COVID-19 infection among patients consulting at an emergency service]. / Evaluación de los predictores clínicos de infección respiratoria aguda por coronavirus SARS-CoV-2 en población adulta.

BACKGROUND: COVID-19 is a serious public health problem worldwide. AIM: To describe the clinical features of COVID-19 infection in adult patients consulting at an Emergency Service. MATERIAL AND METHODS: Descriptive prospective study of adult patients with suspected COVID-19 consulting between April 1 and July 31, 2020, at the Emergency Service of a clinical hospital. Clinical features, chronic comorbidities and demographic data were recorded. RESULTS: We assessed 2,958 adult patients aged 42 ± 15 years (46% males). In 54% of them, COVID-19 infection was confirmed, 40% had preexisting diseases, especially hypertension (15%), hypothyroidism (6%), diabetes (6%), asthma (5%) and obesity (6%). The main clinical manifestations associated with COVID-19 were general malaise (79%), anorexia (38%), myalgia (64%), fever (52%), headache (70%), anosmia/dysgeusia (60%), cough (56%), dyspnea (54%) and diarrhea (36%). In the multivariate analysis, the main clinical predictors of COVID-19 infection were malaise, anorexia, fever, myalgia, headache, nasal congestion, cough, expectoration, anosmia/dysgeusia, and history of close contact with a SARS-CoV-2 patient. Odynophagia and chest discomfort were negative predictors of the disease. The history of fever associated with anorexia, cough, and dyspnea or anosmia/dysgeusia and close contact with a SARS-CoV-2 patient had high specificity and positive predictive value for COVID-19 infection. CONCLUSIONS: Clinical features of COVID-19 infection were highly unspecific in these patients. Clinical diagnostic prediction models could be useful to support healthcare decision making at primary care setting.

Zuccagnia punctata Cav. Essential Oil into Poly(ε-caprolactone) Matrices as a Sustainable and Environmentally Friendly Strategy Biorepellent against Triatoma infestans (Klug) (Hemiptera, Reduviidae)

The main strategies against Triatoma infestans (primary vector responsible for the Chagas disease transmission) are the elimination or reduction of its abundance in homes through the application of insecticides or repellents with residual power, and environmental management through the improvement of housing. The use of plant-derived compounds as a source of therapeutic agents (i.e., essential oils from aromatic plants and their components) is a valuable alternative to conventional insecticides and repellents. Essential oil-based insect repellents are environmentally friendly and provide reliable personal protection against the bites of mosquitoes and other blood-sucking insects. This study investigates, for the first time to our knowledge, the potential repellent activity of Zuccagnia punctata essential oil (ZEO) and poly(ε-caprolactone) matrices loaded with ZEO (ZEOP) prepared by solvent casting. The analysis of its essential oil from aerial parts by GC­FID and GC-MS, MS allowed the identification of 25 constituents representing 99.5% of the composition. The main components of the oil were identified as (−)-5,6-dehydrocamphor (62.4%), alpha-pinene (9.1%), thuja-2, 4 (10)-diene (4.6%) and dihydroeugenol (4.5%). ZEOP matrices were homogeneous and opaque, with thickness of 800 ± 140 µm and encapsulation efficiency values above 98%. ZEO and ZEOP at the lowest dose (0.5% wt./wt., 96 h) showed a repellency of 33 and 73% respectively, while at the highest dose (1% wt./wt., 96 h) exhibited a repellent activity of 40 and 66 %, respectively. On the other hand, until 72 h, ZEO showed a strong repellent activity against T. infestans (88% repellency average; Class V) to both concentrations, compared with positive control N-N diethyl-3-methylbenzamide (DEET). The essential oils from the Andean flora have shown an excellent repellent activity, highlighting the repellent activity of Zuccagnia punctata. The effectiveness of ZEO was extended by its incorporation in polymeric systems and could have a potential home or peridomiciliary use, which might help prevent, or at least reduce, Chagas' disease transmission.

Manifestaciones clínicas y predictores de gravedad en pacientes adultos con infección respiratoria aguda por coronavirus SARS-CoV-2

Background: In December 2019, coronavirus disease 2019 (COVID-19) emerged in Wuhan city and spread rapidly throughout China and the world. Aim: To describe the clinical features, risk factors, and predictors of hospitalization in adult patients treated for acute respiratory infections associated with coronavirus SARS-CoV-2. Material and Methods: Descriptive prospective study of ambulatory and hospitalized adult patients with confirmed COVID-19 attended between April 1 and May 31, 2020. Clinical features, chronic comorbidities and demographic data were recorded, and patients were followed for two months as outpatients. Results: We assessed 1,022 adults aged 41 ± 14 years (50% men) with laboratory-confirmed COVID-19. One-third had comorbidities, specially hypertension (12.5%), hypothyroidism (6.6%), asthma (5.4%) and diabetes (4.5%). Hospital admission was required in 11%, 5.2% were admitted to critical care unit and 0.9% were connected to mechanical ventilation. Common symptoms included fatigue (55.4%), fever (52.5%), headache (68.6%), anosmia/dysgeusia (53.2%), dry cough (53.4%), dyspnea (27.4%) and diarrhea (35.5%). One third of patients reported persistence of symptoms at one-month follow-up, specially fatigue, cough and dyspnea. In the multivariate analysis, age, fever, cough, dyspnea and immunosuppression were associated with hospitalization and ICU admission. Age, male sex and moderate-severe dyspnea were associated with requirement of mechanical ventilation. The main predictors of prolonged clinical course were female sex, presence of comorbidities, history of dyspnea, cough, myalgia and abdominal pain. Conclusions: Clinical features of COVID-19 were highly unspecific. Prediction models for severity, will help medical decision making at the primary care setting.

Efficient Multicomponent Synthesis of Diverse Antibacterial Embelin-Privileged Structure Conjugates.

A library of embelin derivatives has been synthesized through a multicomponent reaction from embelin (1), aldehydes and privileged structures such as 4-hydroxycoumarin, 4-hydroxy-2H-pyran-2-one and 2-naphthol, in the presence of InCl3 as catalyst. This multicomponent reaction implies Knoevenagel condensation, Michael addition, intramolecular cyclization and dehydration. Many of the synthesized compounds were active and selective against Gram-positive bacteria, including one important multiresistant Staphylococcus aureus clinical isolate. It was found how the conjugation of diverse privileged substructure with embelin led to adducts having enhanced antibacterial activities.

UHPLC-Q/Orbitrap/MS/MS fingerprinting and antitumoral effects of Prosopis strombulifera (LAM.) BENTH. queous extract on allograft colorectal and melanoma cancer models.

The aqueous extract of the Argentinean native plant, Prosopis strombulifera (PsAE), presents cytotoxicity against human cancer cell lines by inducing cytostasis, necrosis and apoptosis; with diminution of clonogenic survival; without genotoxic effects nor oral animal toxicity. Until now, the chemical extract composition and its in vivo antitumoral properties remain unknown; these studies are the aim of the current work. The PsAE was characterized by chemical fingerprinting and the metabolome was identified by tandem UHPLC-PDA-HESI-Q-orbitrap® mass spectrometry. Colorectal tumors were induced by DMH administration and melanomas resulted from B16-F0 S.C. cells injection; then, animals were treated orally with PsEA. To correlate in vivo results with in vitro cytotoxicity, B16-F0 cell were cultured to determine: cell proliferation and viability by dye exclusion assays, MTT and CFSE dilution; cell cycle distribution by flow cytometry; and immunoblotting of p21cip1, PCNA, cleaved caspase 3, cleaved PARP and TUBA1A. Based on UHPLC-OT-MS and PDA analysis, twenty-six compounds were identified, including: 5 simple organic acids, 4 phenolic acids, 4 procyanidins, 11 flavonoids, and 2 oxylipins. On C57BL6 mice, PsAE significantly increases the median survival on colorectal cancer and reduces the final volume and weight of melanomas. Over cultured cells, the treatment induce over-expression of p21, cytostasis by G2/M cell cycle arrest and apoptosis; while, on in vivo melanomas, treatment up-regulates p21 and slightly decreases PCNA. In conclusion, PsAE is composed by phenolic compounds which demonstrate cytotoxic and antitumoral properties when is orally administrated. Presented results support future research of PsAE as a potential phytomedicine for cancer treatment.

UHPLC-HESI-OT-MS-MS Biomolecules Profiling, Antioxidant and Antibacterial Activity of the "Orange-Yellow Resin" from Zuccagnia punctata Cav.

This research was designed to investigate the metabolite profiling, phenolics, and flavonoids content as well as the potential antioxidant and antibacterial, properties of orange-yellow resin from Zuccagnia punctata Cav (ZpRe). Metabolite profiling was obtained by a ultrahigh resolution liquid chromatography orbitrap MS analysis (UHPLC-ESI-OT-MS-MS). The antioxidant properties were screened by four methods: 2,2-diphenyl-1-picrylhydrazyl assay (DPPH), trolox equivalent antioxidant activity assay (TEAC), ferric-reducing antioxidant power assay (FRAP), and lipid peroxidation in erythrocytes (LP)). The antibacterial activity was evaluated according to the Clinical and Laboratory Standards Institute (CLSI) rules. The resin displayed a strong DPPH scavenging activity (IC50 = 25.72 µg/mL) and showed a percentage of inhibition of LP close to that of the reference compound catechin (70% at 100 µg ZpRe/mL), while a moderated effect was observed in the FRAP and TEAC assays. The resin showed a content of phenolic and flavonoid compounds of 391 mg GAE/g and 313 mg EQ/g respectively. Fifty phenolics compounds were identified by ultrahigh resolution liquid chromatography orbitrap MS analysis (UHPLC-PDA-OT-MS) analysis. Thirty-one compounds are reported for the first time, updating the knowledge on the chemical profile of this species. The importance of the biomolecules identified support traditional use of this endemic plant. Furthermore, additional pharmacological data is presented that increase the potential interest of this plant for industrial sustainable applications.