Computational Investigation of a Series of Small Molecules as Potential Compounds for Lysyl Hydroxylase-2 (LH2) Inhibition.

The catalytic function of lysyl hydroxylase-2 (LH2), a member of the Fe(II)/αKG-dependent oxygenase superfamily, is to catalyze the hydroxylation of lysine to hydroxylysine in collagen, resulting in stable hydroxylysine aldehyde-derived collagen cross-links (HLCCs). Reports show that high amounts of LH2 lead to the accumulation of HLCCs, causing fibrosis and specific types of cancer metastasis. Some members of the Fe(II)/αKG-dependent family have also been reported to have intramolecular O2 tunnels, which aid in transporting one of the required cosubstrates into the active site. While LH2 can be a promising target to combat these diseases, efficacious inhibitors are still lacking. We have used computational simulations to investigate a series of 44 small molecules as lead compounds for LH2 inhibition. Tunneling analyses indicate the existence of several intramolecular tunnels. The lengths of the calculated O2-transporting tunnels in holoenzymes are relatively longer than those in the apoenzyme, suggesting that the ligands may affect the enzyme's structure and possibly block (at least partially) the tunnels. The sequence alignment analysis between LH enzymes from different organisms shows that all of the amino acid residues with the highest occurrence rate in the oxygen tunnels are conserved. Our results suggest that the enolate form of diketone compounds establishes stronger interactions with the Fe(II) in the active site. Branching the enolate compounds with functional groups such as phenyl and pyridinyl enhances the interaction with various residues around the active site. Our results provide information about possible leads for further LH2 inhibition design and development.

Improving the sensitivity of gastrointestinal helminth detection using the Mini-FLOTAC technique in wild birds.

High-performance-validated tests are essential for successful epidemiological monitoring, surveillance of parasitic infections, and comparative studies in wildlife populations. The Mini-FLOTAC is a novel flotation-based technique for the sensitive detection and quantification of gastrointestinal parasites that is recently being explored for use in wildlife. A limitation of any flotation-based copromicroscopic method is the selection of the flotation solution (FS), which might influence the performance of the test. However, no study has compared the influence of using different FS in the Mini-FLOTAC technique for parasite detection in wild birds. Here, we evaluated the diagnostic performance of the Mini-FLOTAC in three waterbird host species using two widely used FS: saturated salt (NaCl; specific gravity 1.20) and saturated zinc sulfate (ZnSO4; specific gravity 1.35). One hundred fresh fecal samples were analyzed for parasite fecal egg counts (FEC). Regardless of the host species, fecal samples evaluated with the Mini-FLOTAC method using ZnSO4 resulted in a significantly higher detection rate and higher FEC of strongylid, capillarid, cestode, and trematode parasites, than samples analyzed with the NaCl solution. Our concise study demonstrated the importance of using an appropriate FS for the identification of parasite eggs in wildlife species, especially in hosts with an expected aggregated distribution and low parasite load such as waterbird hosts. The higher analytical sensitivity of the Mini-FLOTAC technique achieved with ZnSO4, and its applicability to fieldwork, highlights this method as a promising tool for the quantitative surveillance of parasite infections in wild bird populations.

Impact of the COVID-19 pandemic in the time to endoscopy in patients with upper gastrointestinal bleedin.

INTRODUCTION: During the COVID-19 pandemic, endoscopic procedures are associated with a high risk of SARS-CoV-2 infection. However, in cases of upper gastrointestinal bleeding (UGIB), priority should be given to an early endoscopy. OBJECTIVE: The main objective was to compare the time since arrival at the hospital and the performance of the endoscopy between both groups. MATERIALS AND METHODS: We performed a retrospective study. Data contains information of patients who attended to the hospital with UGIB and underwent an endoscopy between October 19th, 2019 and June 6th, 2020. Patients were divided into 2 phases: pre-pandemic and pandemic. The time between arrival at the hospital and the performance of the endoscopy in both phases were compared as well as other indicators such hospital stay and in-hospital mortality. RESULTS: With information from 219 patients, the median age was 69 years. 154 and 65 endoscopies were performed in pre-pandemic and pandemic phase, respectively. The time between arrival at the hospital and the performance of the endoscopy was significantly longer during the pandemic (10.00 vs. 13.08 hours, p-value = 0.019). Nevertheless, there were no significant differences in hospital stay or mortality. CONCLUSION: The management of patients with UGIB during the COVID-19 pandemic is complex and requires the application of clinical judgment to decide the best timing to perform an endoscopy without affecting patient care.

Anthelmintic activity of chicory (Cichorium intybus): in vitro effects on swine nematodes and relationship to sesquiterpene lactone composition.

Chicory is a perennial crop that has been investigated as a forage source for outdoor-reared ruminants and pigs, and has been reported to have anthelmintic properties. Here, we investigated in vitro anthelmintic effects of forage chicory-extracts against the highly prevalent swine parasites Ascaris suum and Oesophagostomum dentatum. Methanol extracts were prepared and purified from two different cultivars of chicory (Spadona and Puna II). Marked differences were observed between the anthelmintic activity of extracts from the two cultivars. Spadona extracts had potent activity against A. suum third (L3) and fourth (L4) - stage larvae, as well as O. dentatum L4 and adults, whereas Puna II extracts had less activity against A. suum and no activity towards O. dentatum L4. Transmission-electron microscopy of A. suum L4 exposed to Spadona extracts revealed only subtle changes, perhaps indicative of a specific anthelmintic effect rather than generalized toxicity. Ultra-high liquid chromatography-mass spectrometry analysis revealed that the purified extracts were rich in sesquiterpene lactones (SL), and that the SL profile differed significantly between cultivars. This is the first report of anthelmintic activity of forage chicory towards swine nematodes. Our results indicate a significant anthelmintic effect, which may possibly be related to SL composition.

Anthelmintic effects of forage chicory (Cichorium intybus) against gastrointestinal nematode parasites in experimentally infected cattle.

Two experiments studied the effects of dietary chicory against gastrointestinal nematodes in cattle. In Experiment (Exp.) 1, stabled calves were fed chicory silage (CHI1; n = 9) or ryegrass/clover hay (CTL1; n = 6) with balanced protein/energy intakes between groups. After 16 days, all calves received 10 000 Ostertagia ostertagi and 66 000 Cooperia oncophora third-stage larvae (L3) [day (D) 0 post-infection (p.i.)]. In Exp. 2, calves were assigned to pure chicory (CHI2; n=10) or ryegrass/clover (CTL2; n = 10) pastures. After 7 days, animals received 20 000 O. ostertagi L3/calf (D0 p.i.) and were moved regularly preventing pasture-borne infections. Due to poor regrowth of the chicory pasture, CHI2 was supplemented with chicory silage. At D40 p.i. (Exp. 1) and D35 p.i. (Exp. 2) calves were slaughtered for worm recovery. In Exp.1, fecal egg counts (FEC) were similar between groups. However, O. ostertagi counts were significantly reduced in CHI1 by 60% (geometric mean; P < 0·01), whereas C. oncophora burdens were unaffected (P = 0·12). In Exp. 2, FEC were markedly lowered in CHI2 from D22 p.i onwards (P < 0·01). Ostertagia ostertagi adult burdens were significantly reduced in CHI2 by 66% (P < 0·001). Sesquiterpene lactones were identified only in chicory (fresh/silage). Chicory shows promise as an anti-Ostertagia feed for cattle and further studies should investigate its on-farm use.

[Skin manifestations in adults with a liver allograft]. / Manifestaciones cutáneas en adultos con trasplante hepático del Hospital Clínico de la Universidad de Chile.

BACKGROUND: Skin manifestations after liver transplantation are increasing due to long term immunosuppressive therapy along with an increase in patient survival. Several studies have reported dermatologic complications following renal transplant, but few have studied dermatologic problems after liver transplantation. AIMS: To describe the different types of cutaneous lesions encountered in adults receiving a liver allograft. To evaluate the frequency of cutaneous manifestations of patients in the liver transplant waiting list. MATERIAL AND METHODS: Eighty patients submitted to a liver transplant and 70 patients in the liver transplant waiting list were evaluated with a complete dermatological physical examination. RESULTS: Sixty one percent of patients with a liver allograft had at least one skin manifestation. Of these, 34% had superficial fungal infections, 31% had viral infections, 20% had cutaneous side effects due to immunosuppressive treatment, 10% had malignant lesions, 2% had bacterial infections and one patient had a graft versus host disease. Only 28% of patients in the liver transplant waiting list had dermatologic problems, and the vast majority were lesions linked to liver cirrhosis. CONCLUSIONS: Cutaneous infections were the most common skin problems in liver transplant patients. Although neoplastic lesions are the most commonly mentioned lesions in the literature, only a 10% of our liver transplant patients presented these type of lesions.

Soft-Tissue Anaplastic Lymphoma Kinase-Positive Anaplastic Large Cell Lymphoma in a Child Unmasked by COVID-19.

Anaplastic large cell lymphoma (ALCL) is children's most common mature T-cell neoplasm. The majority is positive for anaplastic lymphoma kinase (ALK). Initial presentation as a soft-tissue pelvic mass without nodal involvement is rare and can be easily misdiagnosed. We report a case of a 12-year-old male presenting with pain and movement restriction in the right extremity. Computed tomography (CT) scan revealed a solitary pelvic mass. Initial biopsy examination concluded rhabdomyosarcoma. After developing pediatric multisystemic inflammatory syndrome due to coronavirus disease 2019 (COVID-19), central and peripheral lymph node enlargement appeared. New cervical adenopathy and pelvic mass biopsies were performed. Immunohistochemistry concluded an ALK-positive ALCL with a small-cell pattern. The patient was treated with brentuximab-based chemotherapy and eventually improved. Differential diagnosis of pelvic masses in children and adolescents must include ALCL. An inflammatory trigger may promote the appearance of a typical nodal disease, previously absent. Attention is warranted during histopathological examination to avoid diagnostic errors.

Borderline Phyllodes Tumor in a Child.

Phyllodes tumor (PT) is considered a rare fibroepithelial tumor. Very few series have been reported in children and adolescents. Based on histopathological features, it can be classified as benign, borderline, or malignant, with the latter having a more aggressive clinical behavior. We report the case of a 10-year-old female who began with an asymptomatic mobile right breast mass. An initial fine needle biopsy (FNB) concluded fibroadenoma (FA). Months later, the mass kept growing, with the appearance of pain and nipple discharge. Benign PT was demonstrated in a new biopsy. A total mastectomy was performed. The post-surgical histopathological examination was compatible with a borderline PT. The patient is now symptom-free and with no signs of relapse. Not all breast masses in the pediatric or adolescent age bracket are FA. Attention is warranted when the clinical behavior does not follow the usual outline. PT has to be considered as a possible diagnosis and treated accordingly.

Effect of temperature and nucleotide on the binding of BiP chaperone to a protein substrate.

BiP (immunoglobulin heavy-chain binding protein) is a Hsp70 monomeric ATPase motor that plays broad and crucial roles in maintaining proteostasis inside the cell. Structurally, BiP is formed by two domains, a nucleotide-binding domain (NBD) with ATPase activity connected by a flexible hydrophobic linker to the substrate-binding domain. While the ATPase and substrate binding activities of BiP are allosterically coupled, the latter is also dependent on nucleotide binding. Recent structural studies have provided new insights into BiP's allostery; however, the influence of temperature on the coupling between substrate and nucleotide binding to BiP remains unexplored. Here, we study BiP's binding to its substrate at the single molecule level using thermo-regulated optical tweezers which allows us to mechanically unfold the client protein and explore the effect of temperature and different nucleotides on BiP binding. Our results confirm that the affinity of BiP for its protein substrate relies on nucleotide binding, by mainly regulating the binding kinetics between BiP and its substrate. Interestingly, our findings also showed that the apparent affinity of BiP for its protein substrate in the presence of nucleotides remains invariable over a wide range of temperatures, suggesting that BiP may interact with its client proteins with similar affinities even when the temperature is not optimal. Thus, BiP could play a role as a "thermal buffer" in proteostasis.

Molecular pathogen screening of louse flies (Diptera: Hippoboscidae) from domestic and wild ruminants in Austria.

BACKGROUND: Hippoboscid flies (Diptera: Hippoboscidae), also known as louse flies or keds, are obligate blood-sucking ectoparasites of animals, and accidentally of humans. The potential role of hippoboscids as vectors of human and veterinary pathogens is being increasingly investigated, but the presence and distribution of infectious agents in louse flies is still unknown in parts of Europe. Here, we report the use of molecular genetics to detect and characterize vector-borne pathogens in hippoboscid flies infesting domestic and wild animals in Austria. METHODS: Louse flies were collected from naturally infested cattle (n = 25), sheep (n = 3), and red deer (n = 12) across Austria between 2015 and 2019. Individual insects were morphologically identified to species level and subjected to DNA extraction for molecular pathogen screening and barcoding. Genomic DNA from each louse fly was screened for Borrelia spp., Bartonella spp., Trypanosomatida, Anaplasmataceae, Filarioidea and Piroplasmida. Obtained sequences of Trypanosomatida and Bartonella spp. were further characterized by phylogenetic and haplotype networking analyses. RESULTS: A total of 282 hippoboscid flies corresponding to three species were identified: Hippobosca equina (n = 62) collected from cattle, Melophagus ovinus (n = 100) from sheep and Lipoptena cervi (n = 120) from red deer (Cervus elaphus). Molecular screening revealed pathogen DNA in 54.3% of hippoboscids, including infections with single (63.39%), two (30.71%) and up to three (5.90%) distinct pathogens in the same individual. Bartonella DNA was detected in 36.9% of the louse flies. Lipoptena cervi were infected with 10 distinct and previously unreported Bartonella sp. haplotypes, some closely associated with strains of zoonotic potential. DNA of trypanosomatids was identified in 34% of hippoboscids, including the first description of Trypanosoma sp. in H. equina. Anaplasmataceae DNA (Wolbachia spp.) was detected only in M. ovinus (16%), while < 1% of the louse flies were positive for Borrelia spp. and Filarioidea. All hippoboscids were negative for Piroplasmida. CONCLUSIONS: Molecular genetic screening confirmed the presence of several pathogens in hippoboscids infesting domestic and wild ruminants in Austria, including novel pathogen haplotypes of zoonotic potential (e.g. Bartonella spp.) and the first report of Trypanosoma sp. in H. equina, suggesting a potential role of this louse fly as vector of animal trypanosomatids. Experimental transmission studies and expanded monitoring of hippoboscid flies and hippoboscid-associated pathogens are warranted to clarify the competence of these ectoparasites as vectors of infectious agents in a One-Health context.

[Diagnostic capacity of neck circumference to evaluate obesity in a young adult population. Data analysis from the second national health survey in Chile, 2009-2010]. / Capacidad diagnóstica de la circunferencia de cuello para evaluar la obesidad en la población adulta joven. Análisis de datos de la segunda Encuesta Nacional de Salud 2009-2010. Chile.

Introduction: Introduction: Chile is among the countries with the highest rate of excess malnutrition, for that reason it is important to have effective tools to evaluate the nutritional status; interest in neck circumference (NC) measurement as a potential prognostic tool that is easy to access and low-cost has increased. Objective: to evaluate the diagnostic capacity of neck circumference to predict obesity in the population aged 15-16 years, using data from the third National Health Survey 2009-2010. Materials and methods: Concurrent Criteria of Diagnostic Validation were used for the study. The sample consisted of 536 people of ages from 15 to 26 years, where BMI data where taken in order to classify obesity versus normality (gold standard), as was NC (measured in centimeters). People with hyperthyroidism were excluded. Indicators of diagnostic accuracy were obtained; the SPSS, version 25 was used for calculations. Results: according to age and gender ranks, the NC cut-off points to classify general obesity showed sensitivities and specificities above 0.85, with an area under the curve over 0.90, all with p < 0.001. Conclusion: there is evidence that supports that NC cutoff points are a suitable tool for diagnosing obesity in this age group.

Introducción: Introducción: Chile está dentro de los países con mayor tasa de malnutrición por exceso, lo que obliga a disponer de herramientas eficaces para evaluar el estado nutricional; así surge nuestro interés por explorar la posibilidad de utilizar la medición de la circunferencia del cuello (CCUE) como herramienta potencial de diagnóstico de fácil obtención y acceso, y bajo costo. Objetivo: evaluar la capacidad diagnóstica de la circunferencia del cuello como predictor de obesidad en la población de 15-26 años de edad. Materiales y métodos: dado que se encuentran disponibles, y son adecuados para nuestra investigación, se utilizarán datos extraídos de la Tercera Encuesta Nacional de Salud 2009-2010. Nuestro estudio se realizó aplicando el Método de Validación Diagnóstica por Criterio Concurrente. La muestra estuvo compuesta por 536 personas cuyas edades fluctuaban entre los 15 y 26 años, de quienes se tomaron los datos de IMC, para clasificarlas en las categorías de obesidad o normalidad (patrón oro), y la CCUE (en centímetros). Se excluyeron las personas con hipertiroidismo. Se obtuvieron indicadores de exactitud diagnóstica y valores predictivos. Se aplicó el SPSS, versión 25. Resultados: según los rangos de edad y el sexo, los puntos de corte de la CCUE para clasificar la obesidad general presentaron sensibilidades y especificidades superiores a 0,85 con una área bajo la curva superior a 0,90, todos con p < 0,001. Conclusión: existe evidencia a favor de que los puntos de corte de la CCUE presentan una adecuada capacidad de diagnosticar la obesidad en este grupo etario.

Anti-protozoal activity and metabolomic analyses of Cichorium intybus L. against Trypanosoma cruzi.

Chagas disease, caused by the protozoa Trypanosoma cruzi, is a potentially life-threatening parasitic zoonosis infecting 6-7 million people worldwide, mainly in Latin America. Due to the limited numbers of drugs available against this neglected disease and their frequent adverse effects, novel anti-chagasic agents are urgently needed. Cichorium intybus L. (chicory) is a bioactive plant with potent activity against parasitic nematodes, but its effects on protozoans are poorly known and no studies have explored its trypanocidal potential. Here, we investigated the activity of C. intybus against extracellular and intracellular stages of T. cruzi, including the prediction of trypanocidal compounds by metabolomic analyses and bioactivity-based molecular networking. Purified C. intybus extracts were prepared from leaves and roots of five C. intybus cultivars (cv. 'Benulite', 'Goldine', 'Larigot', 'Maestoso' and 'Spadona'). All C. intybus extracts induced concentration-dependent effects against T. cruzi trypomastigotes. C. intybus leaf extracts had higher trypanocidal selectivity and lower cytotoxicity on mammalian cells than root extracts. The leaf extract of C. intybus cv. Goldine also significantly reduced the number of mammalian cells infected with T. cruzi amastigotes. Metabolomic and bioactivity-based molecular networking analyses revealed 11 compounds in C. intybus leaves strongly linked with activity against trypomastigotes, including the sesquiterpene lactone lactucin, and flavonoid- and fatty acid-derivatives. Furthermore, seven distinct C. intybus molecules (including two sesquiterpene lactone-derivatives) were predicted to be involved in reducing the number of mammalian cells infected with amastigotes. This is the first report of the anti-protozoal activity of C. intybus against trypanosomatid parasites and expands our understanding of the anti-parasitic effects of this plant and its bioactive metabolites. Further studies to elucidate the anti-protozoal compound(s) in C. intybus and their mode(s) of action will improve our knowledge of using this bioactive plant as a promising source of novel broad-spectrum anti-parasitic compounds with associated health benefits and biomedical potential.

A Method to Estimate the Efficacy vs. Effectiveness in Meta-Analysis of Clinical Trials with Different Adherence Scenarios: A Monte Carlo Simulation Study in Nutrition.

Randomized clinical trials (RCTs) evaluating the effectiveness of interventions to promote fruit and vegetable (FV) consumption usually report intention-to-treat (ITT) analysis as the main outcome. These analyses compare the randomly assigned groups and accept that some individuals may not follow the recommendations received in their group. The ITT analysis is useful to quantify the global effect of promoting the consumption of FV in a population (effectiveness) but, if non-adherence is significant in the RCT, they cannot estimate the specific effect in the individuals that increased their FV consumption (efficacy). To calculate the efficacy of FV consumption, a per protocol analysis (PP) would have to be carried out, in which groups of individuals are compared according to their actual adherence to FV consumption, regardless of the group to which they were assigned; unfortunately, many RCTs do not report the PP analysis. The objective of this article is to apply a new method to estimate the efficacy of Meta-analysis (MA) PP which include RCTs of effectiveness by ITT, without estimates of adherence. The method is based on generating Monte Carlo simulations of percentages of adherence in each allocation group from prior distributions informed by expert knowledge. We illustrate the method reanalyzing a Cochrane Systematic Review (SR) of RCTs on increased FV consumption reported with ITT, simulating 1000 times the estimation of a PP meta-analyses, and obtaining means and ranges of the potential PP effects. In some cases, the range of estimated PP effects was clearly more favourable than the effect calculated with the original ITT assumption, and therefore this corrected analysis must be considered when estimating the true effect of the consumption of a certain food.

Effect of a Ketogenic Diet on the Nutritional Parameters of Obese Patients: A Systematic Review and Meta-Analysis.

The effect of a ketogenic diet (KD) on biochemical parameters and nutritional status has been the subject of debate over the years, as several randomized clinical trials (RCTs) obtained different results. METHOD: A systematic review and random-effects meta-analysis of RCTs comparing KD with a balanced diet was performed by means of a search of PubMed, Cochrane Library, Scopus, and Web of Science. Trials where the method for measuring the response variables was unclear, those that considered pathologies other than chronic non-communicable diseases and those with participants receiving pharmacological treatment for obesity were excluded from the comparison. RESULTS: Of the studies included in the meta-analysis, no statistically significant standardized mean differences were observed for body mass index (BMI) (d = -0.457, p = 0.359), total cholesterol, COL-T (d = 0.230, p = 0.591), high-density lipoprotein, HDL (d = -0.028, p = 0.934), low-density lipoprotein, LDL (d = 0.528, p = 0.173), or triglycerides, TG (d = -0.283, p = 0.222), with high values of heterogeneity. The percentage of women included in the studies is a significant moderating variable in terms of BMI ratio (z = -6.68, p < 0.001) and TG (z = -2.27, p = 0.023). CONCLUSION: A KD shows no more benefits on nutritional parameters than a balanced diet, and adverse effects of being on the diet are sometimes reported.

Bio-Guided Fractionation and Molecular Networking Reveal Fatty Acids to Be Principal Anti-Parasitic Compounds in Nordic Seaweeds.

Widespread use of antimicrobial drugs has led to high levels of drug-resistance in pathogen populations and a need for novel sources of anti-bacterial and anti-parasitic compounds. Macroalgae (seaweed) are potentially a rich source of bioactive compounds, and several species have traditionally been used as vermifuges. Here, we investigated the anti-parasitic properties of four common cold-water Nordic seaweeds; Palmaria palmata (Rhodophyta), Laminaria digitata, Saccharina latissima and Ascophyllum nodosum (Ochrophyta, Phaeophyceae). Screening of organic extracts against helminths of swine (Ascaris suum) and sheep (Teladorsagia circumcincta) revealed that S. latissima and L. digitata had particularly high biological activity. A combination of molecular networking and bio-guided fractionation led to the isolation of six compounds from extracts of these two species identified in both fermented and non-fermented samples. The six isolated compounds were tentatively identified by using MS-FINDER as five fatty acids and one monoglyceride: Stearidonic acid (1), Eicosapentaenoic acid (2), Alpha-Linolenic acid (3), Docosahexaenoic acid (4), Arachidonic acid (5), and Monoacylglycerol (MG 20:5) (6). Individual compounds showed only modest activity against A. suum, but a clear synergistic effect was apparent when selected compounds were tested in combination. Collectively, our data reveal that fatty acids may have a previously unappreciated role as natural anti-parasitic compounds, which suggests that seaweed products may represent a viable option for control of intestinal helminth infections.

Identification of compounds responsible for the anthelmintic effects of chicory (Cichorium intybus) by molecular networking and bio-guided fractionation.

Increasing resistance towards anthelmintic drugs has necessitated the search for alternative treatments for the control of gastrointestinal nematode parasites. Animals fed on chicory (Cichorium intybus L.), a temperate (pasture) crop, have reduced parasite burdens, hence making C. intybus a potentially useful source for novel anthelmintic compounds or a diet-based preventive/therapeutic option. Here, we utilized in vitro bioassays with the parasitic nematode Ascaris suum and molecular networking techniques with five chicory cultivars to identify putative active compounds. Network analysis predicted sesquiterpene lactones (SL) as the most likely group of anthelmintic compounds. Further bioassay-guided fractionation supported these predictions, and isolation of pure compounds demonstrated that the SL 8-deoxylactucin (8-DOL) is the compound most strongly associated with anti-parasitic activity. Furthermore, we showed that 8-DOL acts in a synergistic combination with other SL to exert the anti-parasitic effects. Finally, we established that chicory-derived extracts also showed activity against two ruminant nematodes (Teladorsagia circumcincta and Cooperia oncophora) in in vitro assays. Collectively, our results confirm the anti-parasitic activity of chicory against a range of nematodes, and pave the way for targeted extraction of active compounds or selective breeding of specific cultivars to optimize its future use in human and veterinary medicine.

Anthelmintic and metabolomic analyses of chicory (Cichorium intybus) identify an industrial by-product with potent in vitro antinematodal activity.

Chicory (Cichorium intybus) is a bioactive forage rich in sesquiterpene lactones (SLs) with reported in vitro and in vivo anthelmintic activity in livestock. However, the on-farm adoption of chicory as an anthelmintic crop is limited and may be facilitated by using standardised industrial chicory material. Chicory root pulp is a by-product obtained from industrial chicory roots after inulin extraction and can potentially retain SLs. However, SL content and associated anthelmintic activity of chicory root pulp have not been investigated. Here, we evaluated the anthelmintic activity of SL-enriched extracts from chicory root pulp and forage chicory, and used untargeted metabolomics and molecular networking to identify potential anthelmintic molecules. Six different sources of chicory material were used: fresh chicory root pulp (from industrial chicory roots C. intybus var. sativum; "Root Pulp"), fresh leaves from chicory cv. Spadona (sampled on four occasions) and fresh leaves from chicory cv. Choice. The resulting extracts were tested for anthelmintic activity against the free-living nematode Caenorhabditis elegans and the pig nematode Ascaris suum. The cytotoxicity of the chicory extracts was evaluated on mammalian (Vero) cells. In the C. elegans assays, the Root Pulp was the most potent extract and induced paralysis in >95% of worms exposed to >250  µg extract/mL (EC50 = 64.2 µg/mL). In the A. suum assays, the Root Pulp was also the most potent chicory extract to inhibit worm motility (EC50 = 87.6  µg/mL), followed closely by two of the Spadona leaf extracts (EC50 = 89.8  µg/mL and 112.2  µg/mL) The Root Pulp extract had the lowest cytotoxicity of all tested extracts towards mammalian cells, with a selectivity index of 5.37. Untargeted metabolomics revealed that chicory Root Pulp had a markedly different chemical profile in comparison with forage chicory extracts. Molecular networking confirmed several SLs and SL-derivatives mainly present in chicory root pulp, that may be responsible of its potent anti-parasitic activity. Bioactivity-based molecular networking of chicory root pulp and the most potent forage chicory extracts revealed a high predicted anthelmintic score for the guaianolide SL 11,13-dihydro-lactucopicrin. In conclusion, chicory root pulp showed potent and selective in vitro anthelmintic activity against C. elegans and A. suum, with low cytotoxicity in mammalian cells. The promising anthelmintic activity of chicory root pulp should be confirmed in vivo to further explore the potential of this agro-industrial by-product as a nutraceutical anthelmintic for livestock and as novel source of anti-parasitic compounds.

Transcultural adaptation of the Karen Personal instrument to measure the nurses' perception of healthcare quality in hospitals. / Adaptación transcultural del instrumento Karen Personal para medir la percepción de la calidad del cuidado en enfermeras de hospital.

OBJECTIVE: To adapt cross-culturally and validate the Karen Personal scale to measure the perception of the quality of care of hospital nurses of the public health care network in Chile. METHOD: For the transcultural adaptation to Spanish of the scale, the inverse method was applied with translation-back translation and the judgment of 41 nursing professionals from a medium complexity public hospital. Then in a sample of 290 nurses from three high complexity public hospitals, exploratory factor analysis (varimax rotation) and confirmatory (maximum likelihood) and structural equations were applied. The programmes Stata 13.0 and R 3.2.2 were used. RESULTS: A linguistically adapted version of the instrument was obtained and presented a factorial solution of four factors that together explain 63.8% of the variance, and the scale presented a good fit according to the indicators used: CFI (.961); TLI (.950); RMSEA (.65); SRMR (.67). CONCLUSIONS: The abbreviated version proposed in this study was adapted cross-culturally and shows adequate metrics and factorial analysis, it is necessary to continue evaluating its clinimetric properties in future studies.

Huella psicosocial del COVID-19 en enfermeras de 4 países de Latinoamérica, año 2021-2022: aprendizajes y desafíos / Psychosocial footprint of COVID-19 in nurses from 4 South American countries, year 2021-2022: learning and challenges / Pegada psicossocial da COVID-19 em enfermeiros de 4 países da América do Sul, ano 2021-2022: aprendizado e desafios

Objetivo: determinar la huella psicosocial de la pandemia por COVID-19 en enfermeras de 4 países de Sudamérica, año 2021-2022. Métodos: estudio de corte transversal, en una muestra de 279 enfermeras: colombianas (86), paraguayas (68), mexicanas (54) y chilenas (71), que cumplieron los criterios de inclusión.Se aplicaron las escalas de Duke-UNC para evaluar apoyo social recibido y confidencial; El cuestionario Medical Outcomes Study-Social Support Survey (MOS) para evaluar apoyo social y el cuestionario de variables de interacción psicosocial (VIP) Resultados: tanto el buen apoyo confidencial como afectivo, se asoció con las variables de vivir con dos o más personas, ser perteneciente a una religión, y trabajar en una unidad con pacientes. El consumo de medicamentos fue significativamente menor en el grupo con buen apoyo confidencial y afectivo, (p=0.012) Conclusiones:la ejecución del rol profesional de la enfermera es conocido como de alta calidad, y con una destacada responsabilidad, especialmente en pandemia por SAR COVID 19. Sin embargo, se aprecian huellas residuales físicas y emocionales en los profesionales de enfermería.

Objective: to determine the psychosocial footprint of the COVID-19 pandemic in nurses from 4 South American countries, 2021-2022. Methods: cross-sectional study, in a sample of 279 nurses: Colombian (86), Paraguayan (68), Mexican (54) and Chilean (71), who met the inclusion criteria. Duke-UNC scales were applied to assess received and confidential social support; The Medical Outcomes Study-Social Support Survey (MOS) questionnaire to assess social support and the psychosocial interaction variables (VIP) questionnaire. Results: both good confidential and affective support were associated with the variables of living with two or more people, belonging to a religion, and working in a unit with patients. Medication consumption was significantly lower in the group with good confidential and affective support, (p=0.012). Conclusions: the execution of the professional role of the nurse is known to be of high quality, and with outstanding responsibility, especially in the SAR pandemic. COVID 19. However, residual physical and emotional traces can be seen in nursing professionals.

Objetivo determinar a pegada psicossocial da pandemia de COVID-19 em enfermeiros de 4 países da América do Sul, 2021-2022. Métodos: estudo transversal, em uma amostra de 279 enfermeiras: colombianas (86), paraguaias (68), mexicanas (54) e chilenas (71), que atenderam aos critérios de inclusão. As escalas de Duke-UNC foram aplicadas para avaliar o suporte social recebido e confidencial; o questionário Medical Outcomes Study-Social Support Survey (MOS) para avaliar o apoio social e o questionário de variáveis de interação psicossocial (VIP). Resultados: tanto o bom apoio confidencial quanto o afetivo estiveram associados às variáveis morar com duas ou mais pessoas, pertencer a uma religião e trabalhar em unidade com pacientes. O consumo de medicamentos foi significativamente menor no grupo com bom apoio confidencial e afetivo, (p=0,012). Conclusões: sabe-se que o desempenho da função profissional do enfermeiro é de alta qualidade, e com destacada responsabilidade, principalmente na pandemia SAR COVID 19. No entanto, traços residuais físicos e emocionais podem ser observados nos profissionais de enfermagem.