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Background: Obesity is a major public health concern worldwide. Latin America has experienced rapid growth in obesity incidence during the last few decades. Driven by confinement measures, a telemedicine program was implemented in March 2020 to give continuity to obese patients' care through a weight loss program led by the endocrinology department in a tertiary care medical center in Latin America., Objective: This study aimed to describe the clinical experience of using digital health for monitoring and attention of obese patients and description of weight change outcomes of these patients followed via telemedicine during March 2020-December 2020., Methods: A retrospective cohort study was conducted including 202 patients. A Skillings-Mack test was performed to conduct a subgroup analysis of the medians of the weight over the follow-up period, and a mixed multiple linear regression model was performed to estimate the expected average change in weight over time Results: We observed good adherence to the program, represented by a weight loss of -4.1 kg at three months of follow-up, which was maintained even during the sixth month of follow-up., Conclusions: Digital Health strategies such as telemedicine can be a helpful tool for both patients and health care providers to support the continuity of care and showing satisfactory results in the management of obese patients.

Rhizosphere microbial communities exert critical roles in plant health, nutrient cycling, and soil fertility. Despite the essential functions conferred by microbes, the source and acquisition of the rhizosphere are not entirely clear. Therefore, we investigated microbial community diversity and potential source using the only two native Antarctic plants, Deschampsia antarctica (Da) and Colobanthus quitensis (Cq), as models. We interrogated rhizosphere and bulk soil microbiomes at six locations in the Byers Peninsula, Livingston Island, Antarctica, both individual plant species and their association (Da.Cq). Our results show that host plant species influenced the richness and diversity of bacterial communities in the rhizosphere. Here, the Da rhizosphere showed the lowest richness and diversity of bacteria compared to Cq and Da.Cq rhizospheres. In contrast, for rhizosphere fungal communities, plant species only influenced diversity, whereas the rhizosphere of Da exhibited higher fungal diversity than the Cq rhizosphere. Also, we found that environmental geographic pressures (i.e., sampling site, latitude, and altitude) and, to a lesser extent, biotic factors (i.e., plant species) determined the species turnover between microbial communities. Moreover, our analysis shows that the sources of the bacterial communities in the rhizosphere were local soils that contributed to homogenizing the community composition of the different plant species growing in the same sampling site. In contrast, the sources of rhizosphere fungi were local (for Da and Da.Cq) and distant soils (for Cq). Here, the host plant species have a specific effect in acquiring fungal communities to the rhizosphere. However, the contribution of unknown sources to the fungal rhizosphere (especially in Da and Da.Cq) indicates the existence of relevant stochastic processes in acquiring these microbes. Our study shows that rhizosphere microbial communities differ in their composition and diversity. These differences are explained mainly by the microbial composition of the soils that harbor them, acting together with plant species-specific effects. Both plant species acquire bacteria from local soils to form part of their rhizosphere. Seemingly, the acquisition process is more complex for fungi. We identified a significant contribution from unknown fungal sources due to stochastic processes and known sources from soils across the Byers Peninsula., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Guajardo-Leiva, Alarcón, Gutzwiller, Gallardo-Cerda, Acuña-Rodríguez, Molina-Montenegro, Crandall, Pérez-Losada and Castro-Nallar.)

Major Depressive Disorder is a chronic, recurring, and potentially fatal disease, affecting up to 20% of the global population. Since the monoamine hypothesis was proposed more than 60 years ago, only a few relevant advances have been made, with very little disease course changing from a pharmacological perspective. Moreover, since the negative efficacy of novel molecules is frequently reported in studies, many pharmaceutical companies have put new studies on hold. Fortunately, relevant clinical studies are currently being performed extensively, developing immense interest among universities, research centers, and other public and private institutions. Depression is no longer considered a simple disease but a multifactorial one. New research fields are emerging, occurring a paradigm shift, such as the multi-target approach beyond monoamines. In this review, we summarize antidepressant drug discovery aiming to shed some light on the current state-of-the-art clinical and preclinical advances to face this increasingly devastating disease., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The purpose of this study was to determine the inhibitory capacity of ceanothanes triterpenes isolate from Chilean Rhamnaceae on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. Seven ceanothanes triterpenes were isolated from aerial parts of plant material by classical phytochemical methods or prepared by the hemisynthetic method. Structures were determined by the spectroscopic method (1H-NMR and 13C NMR) and mass spectrometry (MS). AChE and BChE activity were determined by the Ellmann method for all compounds. All tested compounds exerted a greater affinity to AChE than to BChE, where compound 3 has an IC50 of 0.126 uM for AChE and of >500 uM to BChE. Kinetic studies indicated that its inhibition was competitive and reversible. According to the molecular coupling and displacement studies of the propidium iodide test, the inhibitory effect of compound 3 would be produced by interaction with the peripheral anionic site (PAS) of AChE. The compounds tested (1−7) showed an important inhibitory activity of AChE, binding to PAS. Therefore, inhibitors that bind to PAS would prevent the formation of the AChE-Aβ complex, constituting a new alternative in the treatment of Alzheimer’s disease (AD).

The early detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using the real-time quantitative polymerase chain reaction (RT-qPCR) as a gold-standard molecular tool has allowed to test and trace the viral spread and the isolation of COVID-19-infected patients. The detection capacity of viral and internal genes is an essential parameter to consider and analyze during the assay. In this study, we analyze the performance of the two commercial RT-qPCR kits used in Chile, TaqMan™ 2019-nCoV Control Kit v1 (Thermo Fisher) and MaxCov19 (TAAG Genetics), for the COVID-19 diagnosis from nasopharyngeal swab samples (NPSs). Our results show a lower sensitivity of the TAAG kit compared to the Thermo Fisher kit, even in the detection of SARS-CoV-2 mutations associated with its variants. This study reinforces the relevance of evaluating the performance of RT-qPCR kits before being used massively since those with lower sensitivity can generate false negatives and produce outbreaks of local infections., Competing Interests: All authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Roberto Luraschi et al.)

The overexpression of miR-218-5p in cervical cancer (CC) cell lines decreases migration, invasion and proliferation. The objective was to identify target genes of miR-218-5p and the signaling pathways and cellular processes that they regulate. The relationship between the expression of miR-218-5p and RUNX2 and overall survival in CC as well as the effect of the exogenous overexpression of miR-218-5p on the level of RUNX2 were analyzed. The target gene prediction of miR-218-5p was performed in TargetScan, miRTarBase and miRDB. Predicted target genes were subjected to gene ontology (GO) and pathway enrichment analysis using the Kyoto Encyclopaedia of Genes and Genomes (KEGG). The miR-218-5p mimetic was transfected into C-33A and CaSki cells, and the miR-218-5p and RUNX2 levels were determined by RT-qPCR. Of the 118 predicted targets for miR-218-5p, 86 are involved in protein binding, and 10, including RUNX2, are involved in the upregulation of proliferation. Low miR-218-5p expression and a high level of RUNX2 are related to poor prognosis in CC. miR-218-5p overexpression is related to decreased RUNX2 expression in C-33A and CaSki cells. miR-218-5p may regulate RUNX2, and both molecules may be prognostic markers in CC.

Few kinetic parameters, or reaction rates, are known up to date in detail about 1-chloro and 1-fluoro-2,4-dinitrobenzene (ClDNB and FDNB, respectively) with a series of biothiols in aqueous media. These biological nucleophiles with thiol groups have been widely used as a reference in nucleophile reactivity assays due to their prevalence and cellular abundance. The main aim of this study was to elucidate the reaction mechanism based on Brönsted-type plots and reactivity patterns of the electrophile/nucleophile pairs. A complete kinetic study was performed in terms of the comparison of Brönsted-type slope parameters ( β nuc ) for the reactions and was used for assigning the mechanism and the rate-determining step associated with the reaction route. A mass spectrometry analysis demonstrated that the nucleophilic center of the biothiols is the -SH group and there is only one kinetic product. The kinetic study suggests that the reaction mechanism might be the borderline between concerted and stepwise pathways. An amine-enol equilibrium for the most reactive nucleophiles appears to be the main determining factor controlling the nucleophilic attack in the nucleophilic aromatic substitution reactions investigated, highlighting the anionic form for these nucleophiles. This amine-enol equilibrium involves a hydrogen bond which stabilizes the intermediate species in the reaction pathway. Thus, intramolecular bonds are formed and enhance the nucleophilic strength through the contribution of the solvent surrounding the electrophile/nucleophile pairs. Finally, we highlight the importance of the formation of electrophile/nucleophile adducts that could modify structures and/or functions of biological systems with potential toxic effects. Therefore, it is essential to know all these kinetic and reactivity patterns and their incidence on other studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Campodónico, Alarcón-Espósito and Olivares.)

The infections and deaths resulting from Coronavirus Disease 2019 (COVID-19) triggered the need for some governments to make COVID-19 vaccines mandatory. The present study aims to analyze the position of 3026 adults in Colombia, El Salvador, and Spain regarding the possibility of making COVID-19 vaccine mandatory and the intention to be vaccinated with the booster or possible successive doses. Data from an online survey conducted from August to December 2021 among a non-representative sample of Spanish-speaking countries were collected. Multinomial Logistic Regression Models were used. A total of 77.4% of Colombians were in favor of mandatory vaccination compared to 71.5% of Salvadorians and 65.4% of Spaniards (p < 0.000). Women and people over 65 years of age were the groups most in favor of making the vaccine mandatory (p < 0.000). A total of 79.4% said they had received a third dose or would intend to receive the third dose or future doses, if necessary, compared with 9.4% who expressed doubts and 9.9% who refused to be vaccinated or did not intend to be vaccinated. Among the measures that could be taken to motivate vaccination, 63.0% and 60.6% were in favor of requiring a negative test to enter any place of leisure or work, respectively, compared to 16.2% in favor of suspension from work without pay. The acceptance of mandatory vaccination and of third or future doses varies greatly according to sociodemographic characteristics and work environment. As such, it is recommended that policy makers adapt public health strategies accordingly.

In the last two decades, artificial scaffolds for nerve regeneration have been produced using a variety of polymers. Polyhydroxybutyrate (PHB) is a natural polyester that can be easily processed and offer several advantages; hence, the purpose of this review is to provide a better understanding of the efficacy of therapeutic approaches involving PHB scaffolds in promoting peripheral nerve regeneration following nerve dissection in animal models. A systematic literature review was performed following the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" (PRISMA) criteria. The revised databases were: Pub-Med/MEDLINE, Web of Science, Science Direct, EMBASE, and SCOPUS. Sixteen studies were included in this review. Different animal models and nerves were studied. Extension of nerve gaps reconnected by PHB scaffolds and the time periods of analysis were varied. The additives included in the scaffolds, if any, were growth factors, neurotrophins, other biopolymers, and neural progenitor cells. The analysis of the quality of the studies revealed good quality in general, with some aspects that could be improved. The analysis of the risk of bias revealed several weaknesses in all studies. The use of PHB as a biomaterial to prepare tubular scaffolds for nerve regeneration was shown to be promising. The incorporation of additives appears to be a trend that improves nerve regeneration. One of the main weaknesses of the reviewed articles was the lack of standardized experimentation on animals. It is recommended to follow the currently available guidelines to improve the design, avoid the risk of bias, maximize the quality of studies, and enhance translationality.

Patient registries linked to biorepositories constitute a valuable asset for clinical and translational research in oncology. The Spanish Group of Ovarian Cancer Research (GEICO), in collaboration with the Spanish Biobank Network (RNBB), has developed a multicentre, multistakeholder, prospective virtual clinical registry (VCR) associated with biobanks for the collection of real-world data and biological samples of gynaecological cancer patients. This collaborative project aims to promote research by providing broad access to high-quality clinical data and biospecimens for future research according to the needs of investigators and to increase diagnostic and therapeutic opportunities for gynaecological cancer patients in Spain. The VCR will include the participation of more than 60 Spanish hospitals entering relevant clinical information in harmonised electronic case report forms (eCRFs) in four different cohorts: ovarian, endometrial, cervical, and rare gynaecological cancers (gestational trophoblastic disease). Initial data for the cases included till December 2021 are presented. The model described herein establishes a real-world win-win collaboration between multicentre structures, promoted and supported by GEICO, that will contribute to the success of translational research in gynaecological cancer.

The point-in-time (PIT) homeless count conducted annually in communities across the United States is a major metric reported to the federal government that has a number of limitations. With the PIT count in 2021 being optional because of the COVID-19 pandemic and potential increases in homeless-related needs in the aftermath of the pandemic, there are opportunities for renewed efforts to improve how the United States enumerates homelessness, determines needs of communities, and tracks progress in ending homelessness throughout the nation. This article describes 2 divergent solutions: (1) improve the PIT by standardizing methodologies across jurisdictions and supplementing counts with other data sources or (2) replace the PIT with a new system. There are strengths and limitations of both solutions. Advocates for either solution agree that there are important funding considerations to take into account and advancing technologies to utilize. As the nation continues to ramp up public health efforts, homelessness is a public health crisis that could benefit from improved epidemiological and data science methods. ( Am J Public Health . 2022;112(4):633-637. https://doi.org/10.2105/AJPH.2021.306640).

The objective of the present study was to investigate the impact of phenolic-rich avocado peel extract (APE) as an ingredient in beef and soy-based burgers to increase their antioxidant activity, reduce lipid and protein oxidation during gastric digestion, and inhibit urease and anhydrase carbonic activity, which are considered as key factors in the main steps of Helicobacter pylori adhesion in the stomach. The gastric bioaccessible fraction of soy and beef burgers with added 0.5% APE obtained by in vitro digestion exhibited a higher content of phenolic compounds, including monomeric and oligomeric (epi)catechin forms and quercetin, and reduced levels of thiobarbituric acid-reactive substances (TBARS) and carbonyls (49% to 73% and 57% to 60%, respectively) when compared with control burgers. Moreover, the burgers with APE inhibited urease and carbonic anhydrase activity. Results generally showed that including APE reduces the primary risk factors associated with H. pylori infection., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The MeOH:H 2 O (7:3) extracts of leaves from Chilean bean landraces were assessed for total phenolic (TP), total flavonoid (TF), total proanthocyanidin (TPA) content, antioxidant capacity (ORAC, FRAP, TEAC, CUPRAC, DPPH) and the inhibition of enzymes associated with metabolic syndrome (α-glucosidase, α-amylase, pancreatic lipase). The chemical profiles were analyzed by HPLC-DAD. Higher antioxidant activity in the ORAC and CUPRAC assay was found for the landrace Coscorrón, and the best effect in the TEAC for Sapito, respectively. The main phenolics were flavonol glycosides and caffeic acid derivatives. The extracts presented strong activity against α-glucosidase, but were inactive towards α-amylase and pancreatic lipase. The leaf extract from the Sapito landrace was fractionated to isolate the main α-glucosidase inhibitors, leading to caffeoylmalic acid with an IC 50 of 0.21 μg/mL. The HPLC fingerprints of the leaves differentiate three groups of chemical profiles, according to the main phenolic content. A significant correlation was found between the α-glucosidase inhibition, the content of caffeoylmalic acid (r = -0.979) and kaempferol 3-O-β-D-glucoside (r = 0.942) in the extracts. The presence of α-glucosidase inhibitors in the leaves of Chilean beans support their potential as a source of bioactive compounds., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Due to the COVID-19 pandemic, many transport kits have been manufactured to preserve and transport nasopharyngeal swab samples (NPSs) from patients. However, there is no information on the performance of the different virus transport media (VTM) used in COVID-19 diagnosis in the population of Santiago de Chile. We compared the RT-qPCR amplification profile of five different viral transport kit mediums, including DNA/RNA Shield™, NAT, VTM-N, Ezmedlab™, and phosphate-buffered saline (PBS), for NPSs from Central Metropolitan Health Service, Santiago, Chile. The DNA/RNA Shield™ medium showed a better performance in terms of Cq and RFU values for the internal reference RNase P and viral ORF1ab probes. By contrast, the PBS transport medium registered higher Cq values for the viral and reference gene, compared to the other VTM. DNA/RNA Shield™ shows higher relative fluorescence units (RFUs) and lower Cq values for the reference gene. Collectively, our results suggest that the PBS medium could compromise the sample diagnosis because of its lower RT-qPCR performance. The NAT, Ezmedlab and VTM-N, and DNA/RNA Shield™ media show acceptable RT-qPCR parameters and, consequently, seem suitable for use in COVID-19 diagnosis., (© 2021 Wiley Periodicals LLC.)

Background: Increasing evidence highlights the role of muscular strength as a protective factor for cardiometabolic health in adolescents. However, it is not known the relationship between liver enzyme concentrations, liver disease risk factors, and muscular strength among young populations. The aim of this study was to determine the association between muscle strength and liver enzymes and chronic liver disease risk among US adolescents., Methods: Data from the NHANES cross-sectional study (2011-2014) was used. A total of 1270 adolescents were included in the final analysis (12-17 years old). Absolute handgrip strength (kg) was normalized according to body composition parameters by body weight [NHSw], whole-body fat [NHSf], and trunk fat [NHSt])., Results: In boys, handgrip strength was inversely associated with higher values of aspartate aminotransferase (AST) and gamma glutamyl transpeptidase (GGT) for all estimations of muscle strength (NHSw, NHSf, and NHSt) (p < 0.050). Likewise, boys with high and intermediate NHSw, NHSf, and NHSt presented lower AST and GGT than their counterparts with low handgrip strength (p < 0.050)., Conclusions: Our findings highlight the importance of muscular strength during adolescence since they could help in developing better liver enzyme profiles among adolescent population., Impact: Our research suggests that US adolescents with low handgrip strength have higher values of liver enzymes as well as a higher prevalence of chronic liver disease. These findings are clinically meaningful and highlight the importance of muscular strength during adolescence since they could help in developing better liver enzyme profiles among young populations., (© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

The extreme environmental conditions and lack of water on the soil surface in hyperarid deserts hamper microbial life, allowing only highly specialized microbial communities to the establish colonies and survive. Until now, the microbial communities that inhabit or have inhabited soils of hyperarid environments at greater depths have been poorly studied. We analyzed for the first time the variation in microbial communities down to a depth of 3.4 m in one of the driest places of the world, the hyperarid Yungay region in the Atacama Desert, and we related it to changes in soil physico-chemical characteristics. We found that the moisture content changed from 2 to 11% with depth and enabled the differentiation of three depth intervals: (i) surface zone A (0-60 cm), (ii) intermediate zone B (60-220 cm), and (iii) deep zone C (220-340 cm). Each zone showed further specific physicochemical and mineralogical features. Likewise, some bacterial phyla were unique in each zone, i.e., members of the taxa Deinococcota , Halobacterota , and Latescibacterota in zone A; Crenarchaeota , Fusobacteriota , and Deltaproteobacterium Sva0485 in zone B; and Fervidibacteria and Campilobacterota in zone C, which indicates taxon-specific preferences in deep soil habitats. Differences in the microbiota between the zones were rather abrupt, which is concomitant with abrupt changes in the physical-chemical parameters. Overall, moisture content, total carbon (TC), pH, and electric conductivity (EC) were most predictive of microbial richness and diversity, while total sulfur (TS) and total phosphorous (TP) contents were additionally predictive of community composition. We also found statistically significant associations between taxa and soil properties, most of which involved moisture and TC contents. Our findings show that under-explored habitats for microbial survival and existence may prevail at greater soil depths near water or within water-bearing layers, a valuable substantiation also for the ongoing search for biosignatures on other planets, such as Mars., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fuentes, Choque, Gómez, Alarcón, Castro-Nallar, Arenas, Contreras, Mörchen, Amelung, Knief, Moradi, Klumpp, Saavedra, Prietzel, Klysubun, Remonsellez and Bol.)

Cellular behavior in nerve regeneration is affected by the architecture of the polymeric nerve guide conduits (NGCs); therefore, design features of polymeric NGCs are critical for neural tissue engineering. Hence, the purpose of this scoping review is to summarize the adequate quantitative/morphometric parameters of the characteristics of NGC that provide a supportive environment for nerve regeneration, enhancing the understanding of a previous study. 394 studies were found, of which 29 studies were selected. The selected studies revealed four morphometric characteristics for promoting nerve regeneration: wall thickness, fiber size, pore size, and porosity. An NGC with a wall thickness between 250-400 μm and porosity of 60-80%, with a small pore on the inner surface and a large pore on the outer surface, significantly favored nerve regeneration; resulting in an increase in nutrient permeability, retention of neurotrophic factors, and optimal mechanical properties. On the other hand, the superiority of electrospun fibers is described; however, the size of the fiber is controversial in the literature, obtaining optimal results in the range of 300 nm to 30 µm. The incorporation of these optimal morphometric characteristics will encourage nerve regeneration and help reduce the number of experimental studies as it will provide the initial morphometric parameters for the preparation of an NGC.

Background: The potential benefit of adding palbociclib to fulvestrant as first-line treatment in hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative endocrine-sensitive advanced breast cancer (ABC) patients remains uncharacterized., Patients and Methods: In this randomized (1:1), double-blind, phase II study, postmenopausal women with HR-positive, HER2-negative ABC with de novo metastatic disease or those who relapsed after >12 months of adjuvant endocrine therapy received palbociclib/fulvestrant or placebo/fulvestrant. Stratification was based on recurrent versus de novo metastatic disease and visceral involvement. The primary objective was one-year progression-free survival (PFS-1y) rate. The sample size was 190 patients. The two-sided alpha of 0.2, 80% of power to detect a difference between the arms, assuming PFS rates of 0.695 and 0.545 for palbociclib/fulvestrant and placebo/fulvestrant, respectively., Results: In total, 189 patients were randomized to palbociclib/fulvestrant ([n = 94] or placebo/fulvestrant [n = 95]). 45.5% and 60.3% of patients had de novo metastatic disease and visceral involvement, respectively. PFS-1y rates were 83.5% and 71.9% in the palbociclib/fulvestrant and placebo/fulvestrant arms, (HR 0.55, 80% CI 0.36-0.83, P = 0.064). The median PFS were 31.8 and 22.0 months for the palbociclib/fulvestrant and placebo/fulvestrant arms (aHR 0.48, 80% CI 0.37-0.64, P = 0.001). The most frequent grade 3-4 adverse events were neutropenia (68.1% vs. 0%), leucopenia (26.6% vs. 0%), anemia (3.2% vs. 0%), and lymphopenia (14.9% vs. 2.1%) for the palbociclib/fulvestrant and placebo/fulvestrant, respectively. The most frequent non-hematologic grade 3-4 adverse event was fatigue (4.3% vs. 0%)., Conclusions: Palbociclib/fulvestrant demonstrated better PFS-1y rates and median PFS than placebo/fulvestrant in HR-positive/HER2-negative endocrine-sensitive ABC patients., Competing Interests: Conflict of interest statement Joan Albanell has received consulting or advisory role fees from Roche, Pfizer, Amgen, MSD, Lilly and Daiichi-Sankyo; research funding or grant support trials by Roche, Pfizer, Amgen, MSD, Lilly, Daiichi-Sankyo; and travel and accommodation support from Roche, Pfizer, Amgen, MSD, Lilly and Daiichi-Sankyo. Manuel Ramos has received honoraria from Novartis, Roche, and Pfizer. Luis de la Cruz-Merino has received consulting or advisory role fees from MSD-Merck, Roche Farma, Bristol-Myers-Squibb, Pierre-Fabré, Amgen and Novartis; research funding from MSD-Merck, Roche Farma and Celgene; speaker's honoraria from MSD-Merck, Roche-Farma, Bristol-Myers-Squibb and Amgen; and grant support by Roche Farma and Bristol-Myers-Squibb. Ana Santaballa has received consulting or advisory role fees from GSK, Clovis, MSD, AstraZeneca, Roche and Pfizer; speakers' honoraria from GSK, Clovis, Roche, MSD, AstraZeneca and Pfizer; and grant support by Pfizer, GSK and MSD. Noelia Martinez-Janez has received advisory board honorary from Roche, AstraZeneca, Daichi, Pfizer, Novartis, Lilly and Eisai. Fernando Moreno has received consulting or advisory fees from Roche/Genentech, Novartis, Pfizer, AstraZeneca, and MSD; speakers' honoraria from Pfizer and Roche/Genentech; research funding fees from Pfizer; travel and accommodation support from Roche/Genentech, Pfizer and Novartis. Isaura Fernández has received consulting or advisory role fees from AstraZeneca, MSD, GlaxoSmithKline and Roche; research funding from Roche; and speaker's honoraria from Clovis, Pfizer and Novartis. Jesús Alarcón has received honoraria by GSC, Clovis, Roche and AstraZeneca; consulting or advisory board honoraria by GSK and Clovis; speaker and expert testimony fees by GSK, Clovis and Roche; and travel and accommodation support from GSK. Juan de la Haba has received speaker's honoraria from AstraZeneca, Pfizer, Novartis and Lilly. Mireia Margelí has received advisory board fees from Roche, Novartis, Pfizer, and Eisai. Her institution, ICO -Badalona. B-ARGO (Badalona Applied Research Group in Oncology) Hospital Universitari Germans Trias i Pujol, Badalona, has received funding research from Roche, Pfizer, Novartis, Lilly, AstraZeneca, Eisai, and Kern. Antonio Antón has received advisory board fees from Bayer, Spain. Federico Rojo has received consulting or advisory role fees from Roche, Pfizer, Novartis, BMS, Pierre-Fabre, Incyte, Abbvie, Amgen, MSD, and Lilly; and travel and accommodation support from Roche. GEICAM has received research funding from Roche/Genentech, Bristol-Myers Squibb, Novartis, Pfizer, Celgene, AstraZeneca, Merck Sharp & Dohme, Pierre Fabre, and Takeda. All remaining authors have declared no conflicts of interest., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Armoured dinosaurs are well known for their evolution of specialized tail weapons-paired tail spikes in stegosaurs and heavy tail clubs in advanced ankylosaurs 1 . Armoured dinosaurs from southern Gondwana are rare and enigmatic, but probably include the earliest branches of Ankylosauria 2-4 . Here we describe a mostly complete, semi-articulated skeleton of a small (approximately 2 m) armoured dinosaur from the late Cretaceous period of Magallanes in southernmost Chile, a region that is biogeographically related to West Antarctica 5 . Stegouros elengassen gen. et sp. nov. evolved a large tail weapon unlike any dinosaur: a flat, frond-like structure formed by seven pairs of laterally projecting osteoderms encasing the distal half of the tail. Stegouros shows ankylosaurian cranial characters, but a largely ancestral postcranial skeleton, with some stegosaur-like characters. Phylogenetic analyses placed Stegouros in Ankylosauria; specifically, it is related to Kunbarrasaurus from Australia 6 and Antarctopelta from Antarctica 7 , forming a clade of Gondwanan ankylosaurs that split earliest from all other ankylosaurs. The large osteoderms and specialized tail vertebrae in Antarctopelta suggest that it had a tail weapon similar to Stegouros. We propose a new clade, the Parankylosauria, to include the first ancestor of Stegouros-but not Ankylosaurus-and all descendants of that ancestor., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

(1) Background: Type 1 diabetes mellitus (T1DM) people's health-related quality of life (HRQoL) is affected by glycemic control. Regular exercise is strongly recommended to these patients due to its cardiovascular and metabolic benefits. However, a large percentage of patients with T1DM people present a sedentary behavior because of the fear of a post-exercise hypoglycemia event, lack of time, lack of motivation and the complicated management of exercise, glycemic and insulin dose interaction. High-intensity interval training (HIIT) is an efficient and safe methodology since it prevents hypoglycemia and does not require much time, which are the main barriers for this population to doing exercise and increasing physical conditioning. (2) Methods: Nineteen sedentary adults (37 ± 6.5 years) with T1DM, were randomly assigned to 6 weeks of either HIIT (12-16-20 × 30-s intervals interspersed with 1-min rest periods) performed thrice weekly, or to the control group, which did not train. HRQoL, sleep quality, exercise motivation and enjoyment were measured as psychological variables. (4) Results: HRQoL improved in physical and social domains, PF (1.9%); PR (80.3%); GH (16.6); SF (34.1%). Sleep quality improved in the HIIT group by 21.4%. Enjoyment improved by 7% and intrinsic motivation was increased by 13%. (5) Conclusions: We suggest that the 6-week HIIT program used in the present study is safe, since no severe hypoglycemia were reported, and an effective strategy in improving HRQoL, sleep quality, exercise motivation and enjoyment which are important psychological well-being factors in T1DM people.

Background: During the COVID 19 pandemic, direct-to-consumer telehealth (DTC) services allowed patients real-time virtual access to healthcare providers, especially those with an established relationship. In Colombia, this care modality was implemented between 2019 and 2020, under national considerations, it was implemented for outpatient care in a highly complex university hospital in Cali, Colombia., Methods: A descriptive study with prospective information collection was used to describe the implementation of the outpatient teleconsultation care model for patients. We constructed the clinical and process indicators with which we evaluated the model., Findings: A total of 56,560 patients from our institution were treated by virtual outpatient consultation during the first nine months of the health emergency declared by COVID 19 in Colombia. The strategy made it possible to achieve coverage more significant than 100% in Cali and the departments of Colombia. Attention by teleconsultation was 19% of the total ambulatory care. The effectiveness in carrying out scheduled teleconsultations had an overall result of 91.5%. The accessibility results demonstrated the need to strengthen connectivity and accessibility to payments and strengthen technology adoption in the institution, health personnel, and patients., Interpretation: Implementing an outpatient teleconsultation model allowed the continuity of the management with comprehensive coverage nationwide from a highly complex hospital in southwestern Colombia. The indicators' analysis should help strengthen the policies of access to telemedicine, especially with the consequences of the pandemic in low- and middle-income countries. Latin American evidence is necessary to establish the safety profile of telemedicine and the costs associated with the provision., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: To achieve herd immunity, the acceptance of the COVID-19 vaccine by the population, especially healthcare professionals, plays a key role. The objective of the present paper is to address the differences in attitudes among Spanish healthcare professionals compared with the general population regarding COVID-19 vaccination. Methods: This cross-sectional study included data from 2,136 adults ( n = 664 healthcare professionals) from an online survey conducted from May 6 to June 9, 2021. The Vaccination attitudes examination scale was used to measure the negative attitudes toward vaccines. Four subscales: mistrust of vaccine benefit, worries about the unforeseen future effect, concerns about commercial profiteering, and preference for natural immunity were calculated. Generalized linear mixed models were conducted to study these associations. Results: Between 10.2 and 22.6% of the subjects showed high levels of negative attitudes toward vaccines. However, only 1.5% of our sample (2.1% among healthcare professionals) refused to get the COVID-19 vaccine when it was offered because they chose otherwise. Retired people showed the lowest concerns and the highest trust in vaccines. No statistically significant effects were found between working in a healthcare field and having higher positive attitudes toward vaccines. Conclusion: Low levels of rejection against the COVID-19 vaccine were identified in the present sample. However, despite being at a higher risk, health care professionals did not show higher positive attitudes toward vaccines. Furthermore, refusal percentage to vaccination was higher among healthcare professionals compared with non-healthcare professionals. Developing a strategy to increase positive attitudes against the COVID-19 vaccine should be an objective for public health policy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Iguacel, Luna Maldonado, Luna Ruiz-Cabello, Samatán, Alarcón, Ángeles Orte, Santodomingo Mateos and Martínez-Jarreta.)

In this study, the benefits of using avocado peel extract (APE), rich in phenolic compounds, to reduce the oxidation and formation of harmful compounds resulting from cooking, were investigated. Beef and soy-based burgers with the addition of APE (0.5% and 1%) were studied after pan frying concerning proximate and physicochemical characteristics, inhibition of protein and lipid oxidation products (thiobarbituric acid reactive substances [TBARS], hexanal, and carbonyls), heterocyclic aromatic amines (HAs) and acrylamide formation. Sensory analysis was additionally performed. APE-affected proximate composition, protein, fat, and ash contents (%) were found to be markedly higher in APE-incorporated burgers (~28.32 ± 0.29, ~14.00 ± 0.01, and ~1.57 ± 0.05, respectively), compared with the controls (~26.55 ± 0.51, ~12.77 ± 0.32, and ~1.48 ± 0.16, respectively). Lower concentrations of TBARS, hexanal, and carbonyls were observed in APE-treated burgers on Days 1 and 10, post-cooking, compared to controls. Overall, it was found that APE had a greater protective effect than the positive control (sodium ascorbate incorporated) in beef burgers. In soy burgers, the positive control demonstrated pro-oxidant activity. The addition of 0.5% APE was found to inhibit HAs and acrylamide formation in beef and soy burgers. Although the addition of APE affected the color of both meat and soy burgers, it did not impact consumer preference. It was therefore concluded that APE extract might be a suitable clean-label alternative to synthetic antioxidants, and that it can protect and increase the nutritional value of meat and meat-free burgers., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Oral diseases are among the most prevalent non-communicable diseases worldwide, disproportionally affecting vulnerable populations. The Community of Claverito is one of many informal urban floating communities located on the Amazon River in Peru., Objectives: To assess child and caregiver dental health status (DHS) and to measure the associations between child DHS and child and family quality of life in the informal Community of Claverito., Methods: DHS, as measured by decayed and filled teeth (DFT/dft), was recorded for 66 children and 35 caregivers using the WHO Oral Assessment form. Oral health-related quality of life was measured using the Parental-Caregiver Perceptions Questionnaire (P-CPQ). The family impact of child oral disorders was measured using the Family Impact Scale (FIS). Descriptive statistics, correlations, and regression analyses were used to evaluate the associations between DFT/dft, P-CPQ, and FIS scores (p < 0.05)., Findings: The majority of children assessed were female (52%) with a mean age of 9.4 years (SD ± 4.4). The prevalence of untreated child dental caries was 97%. The child and caregiver's mean DFT/dft scores were 6.8 (SD ± 4.5) and 8.7 (SD ± 13.3), respectively. Mean total P-CPQ and total FIS scores were 33.4 and 12.5, respectively. A significant positive association was observed between child DFT/dft scores and total FIS scores (p < 0.01). Significant associations were also observed between child DFT/dft scores and caregiver age (p < 0.01) and child DFT/dft scores and caregiver DFT scores (p < 0.01)., Conclusions: Children and their caregivers living in the Community of Claverito exhibited high levels of dental caries. Children's untreated dental caries were associated with both family's quality of life and caregivers' untreated dental caries. Further research is needed on how improving availability and access to oral health services have the potential to benefit the health of residents of informal communities like the one of Claverito., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2021 The Author(s).)

Background: Neratinib has efficacy in central nervous system (CNS) metastases from HER2-positive metastatic breast cancer (MBC). We report outcomes among patients with CNS metastases at baseline from the phase III NALA trial of neratinib plus capecitabine (N + C) versus lapatinib plus capecitabine (L + C)., Materials and Methods: NALA was a randomized, active-controlled trial in patients who received two or more previous HER2-directed regimens for HER2-positive MBC. Patients with asymptomatic/stable brain metastases (treated or untreated) were eligible. Patients were assigned to N + C (neratinib 240 mg per day, capecitabine 750 mg/m 2 twice daily) or L + C (lapatinib 1,250 mg per day, capecitabine 1,000 mg/m 2 twice daily) orally. Independently adjudicated progression-free survival (PFS), overall survival (OS), and CNS endpoints were considered., Results: Of 621 patients enrolled, 101 (16.3%) had known CNS metastases at baseline (N + C, n = 51; L + C, n = 50); 81 had received prior CNS-directed radiotherapy and/or surgery. In the CNS subgroup, mean PFS through 24 months was 7.8 months with N + C versus 5.5 months with L + C (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.41-1.05), and mean OS through 48 months was 16.4 versus 15.4 months (HR, 0.90; 95% CI, 0.59-1.38). At 12 months, cumulative incidence of interventions for CNS disease was 25.5% for N + C versus 36.0% for L + C, and cumulative incidence of progressive CNS disease was 26.2% versus 41.6%, respectively. In patients with target CNS lesions at baseline (n = 32), confirmed intracranial objective response rates were 26.3% and 15.4%, respectively. No new safety signals were observed., Conclusion: These analyses suggest improved PFS and CNS outcomes with N + C versus L + C in patients with CNS metastases from HER2-positive MBC., Implications for Practice: In a subgroup of patients with central nervous system (CNS) metastases from HER2-positive breast cancer after two or more previous HER2-directed regimens, the combination of neratinib plus capecitabine was associated with improved progression-free survival and CNS outcomes compared with lapatinib plus capecitabine. These findings build on previous phase II and III studies describing efficacy of neratinib in the prevention and treatment of CNS metastases, and support a role for neratinib as a systemic treatment option in the management of patients with HER2-positive brain metastases following antibody-based HER2-directed therapies., (© 2021 The Authors. The Oncologist published by Wiley Periodicals LLC on behalf of AlphaMed Press.)

The importance of balanced dietary habits, which include appropriate amounts of antioxidants to maintain the immune system, has become increasingly relevant during the current SARS-CoV-2/COVID-19 pandemic, because viral infections are characterized by high oxidative stress. Furthermore, the measures taken by governments to control the pandemic have led to increased anxiety, stress, and depression, which affect physical and mental health, all of which are influenced by nutritional status, diet, and lifestyle. The Mediterranean diet (MD), Atlantic diet (AD), and the Dietary Guidelines for Americans all provide the essential vitamins, minerals, and phenolic compounds needed to activate enzymatic and nonenzymatic antioxidant responses. However, viral pandemics such as the current COVID-19 crisis entail high oxidative damage caused by both the infection and the resultant social stresses within populations, which increases the probability and severity of infection. Balanced dietary patterns such as the MD and the AD are characterized by the consumption of fruit, vegetables, legumes, olive oil, and whole grains with low intakes of processed foods and red meat. For a healthy lifestyle in young adults, the MD in particular provides the required amount of antioxidants per day for vitamins D (0.3-3.8 μg), E (17.0 mg), C (137.2-269.8 mg), A (1273.3 μg), B-12 (1.5-2.0 μg), and folate (455.1-561.3 μg), the minerals Se (120.0 μg), Zn (11.0 mg), Fe (15.0-18.8 mg), and Mn (5.2-12.5 mg), and polyphenols (1171.00 mg) needed to maintain an active immune response. However, all of these diets are deficient in the recommended amount of vitamin D (20 μg/d). Therefore, vulnerable populations such as elders and obese individuals could benefit from antioxidant supplementation to improve their antioxidant response. Although evidence remains scarce, there is some indication that a healthy diet, along with supplemental antioxidant intake, is beneficial to COVID-19 patients., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Most of the patients who overcome the SARS-CoV-2 infection do not present complications and do not require a specific follow-up, but a significant proportion (especially those with moderate / severe clinical forms of the disease) require clinicalradiological follow-up. Although there are hardly any references or clinical guidelines regarding the long-term follow-up of post-COVID-19 patients, radiological exams are being performed and monographic surveillance consultations are being set up in most of the hospitals to meet their needs. The purpose of this work is to share our experience in the management of the post-COVID-19 patient in two institutions thathave had a high incidence of COVID-19 and to propose general follow-uprecommendations from a clinical and radiological perspective., (Copyright © 2021 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.)

Skin cancer is a public health problem due to its high incidence. Ultraviolet radiation (UVR) is the main etiological agent of this disease. Photochemoprotection involves the use of substances to avoid damage caused by UV exposure. The aim of this work was to determine the phytochemical fingerprint and photochemoprotective effect against UVB radiation-induced skin damage such as erythema and carcinogenesis of H. mociniana methanolic extract (MEHm). The chemical composition of the MEHm was analysed by LC/ESI-MS/MS. Three quercetin derivatives, two pectinolides, and two caffeic acid derivatives were identified in the methanolic extract. MEHm has antioxidant effect and it is not cytotoxic in HaCaT cells. Phytochemicals from H. mociniana have a photochemopreventive effect because they absorb UV light and protect HaCaT cells from UVR-induced cell death. Also, in SKH-1 mice -acute exposure-, it decreased erythema formation, modulating the inflammatory response, reduced the skin damage according to histological analysis and diminished p53 expression. Finally, MEHm protects from photocarcinogenesis by reducing the incidence and multiplicity of skin carcinomas in SKH-1 mice exposed chronically to UVB radiation., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

ALS2 gene encoding for alsin protein is responsible for neurological disorders due to retrograde degeneration of the upper motor neurons of the pyramidal tracts, inherited in an autosomal recessive manner, and displaying a clinical continuum including the infantile ascending hereditary spastic paraplegiaidentified in three Spanish children presented here.

Recent advances in high-throughput sequencing have enabled the large-scale interrogation of microbiota in the most diverse environments, including host-associated microbiota. This has led to the recognition that the skin microbiota of rorquals is specific and structurally different from that of the ocean. This study reveals the skin microbiome of 85 wild individuals along the Chilean coast belonging to Megaptera novaeangliae, Balaenoptera musculus and Balaenoptera physalus. Alpha diversity analysis revealed significant differences in richness and phylogenetic diversity, particularly among humpback whales from different locations and between blue and humpback whales. Beta diversity was partially explained by host and location but only accounting for up to 17% of microbiota variability (adjusted VPA). Overall, we found that microbiota composition was dominated by bacterial genera such as Cardiobacter, Moraxella, Tenacibaculum, Stenotrophomonas, Flavobacteria and Pseudomonas. We also found that no ASVs were associated with the three rorqual species. Up to four ASVs were specific of a location, indicating a great variability in the microbiota. To the best of our knowledge, this is the first report on the composition and structure of the skin microbiota of whales off the coast of Chile, providing a foundational dataset to understand the microbiota's role in rorquals., (© The Author(s) 2021. Published by Oxford University Press on behalf of FEMS.)

Chemical profiling of Buddleja globosa was performed by high-performance liquid chromatography coupled to electrospray ionization (HPLC-DAD-ESI-IT/MS) and quadrupole time-of-flight high-resolution mass spectrometry (HPLC-ESI-QTOF/MS). The identification of 17 main phenolic compounds in B. globosa leaf extracts was achieved. Along with caffeoyl glucoside isomers, caffeoylshikimic acid and several verbascoside derivatives (β-hydroxyverbascoside and β-hydroxyisoverbascoside) were identified. Among flavonoid compounds, the presence of 6-hydroxyluteolin-7- O -glucoside, quercetin-3- O -glucoside, luteolin 7- O -glucoside, apigenin 7- O -glucoside was confirmed. Campneoside I, forsythoside B, lipedoside A and forsythoside A were identified along with verbascoside, isoverbascoside, eukovoside and martynoside. The isolation of two bioactive phenolic compounds verbascoside and forsythoside B from Buddleja globosa (Buddlejaceae) was successfully achieved by centrifugal partition chromatography (CPC). Both compounds were obtained in one-step using optimized CPC methodology with the two-phase solvent system comprising ethyl acetate-n-butanol-ethanol-water (0.25:0.75:0.1:1, v/v ). Additionally, eight Natural Deep Eutectic Solvents (NADESs) were tested for the extraction of polyphenols and compared with 80% methanol. The contents of verbascoside and luteolin 7- O -glucoside after extraction with 80% methanol were 26.165 and 3.206 mg/g, respectively. Among the NADESs tested in this study, proline- citric acid (1:1) and choline chloride-1, 2- propanediol (1:2) were the most promising solvents. With these NADES, extraction yields for verbascoside and luteolin 7- O -glucoside were 51.045 and 4.387 mg/g, respectively. Taken together, the results of this study confirm that CPC enabled the fast isolation of bioactive polyphenols from B. globosa . NADESs displayed higher extraction efficiency of phenolic and therefore could be used as an ecofriendly alternative to classic organic solvents.

The drying process used to obtain active food additives is critical to ensure its functionality. In this study, freeze- and spray-drying techniques were evaluated for encapsulation of extracts with antioxidant activity from yerba mate ( Ilex paraguariensis ), using maltodextrin (MD) as wall material. Additionally, the oxidative stability in a real food matrix (mayonnaise) was assessed. Both MD addition and drying methods affected the physical properties [moisture content, water activity (a W )] and oxidative stability. MD addition diminished moisture content and prevented polyphenol compounds from degradation. The spray-dried powders displayed the lowest moisture content (1.6 ± 0.3% bs), the highest polyphenol content (135.4 mg GAE/g pure extract), and oxidative stability than the freeze-dried samples. The antioxidant capacity of the encapsulated powder subjected to spray-drying increased the oxidative stability of the mayonnaise (258 ± 32 min) more than the other assayed system (165 ± 5 min). Therefore, a natural spray-dried antioxidant food additive was obtained with potential use in the food industry., Competing Interests: Conflict of interestThe authors declare that there is no conflict of interest regarding the publication of this paper., (© Association of Food Scientists & Technologists (India) 2020.)

Despite their recognised role in HER2-positive (HER2+) breast cancer (BC), the composition, localisation and functional orientation of immune cells within tumour microenvironment, as well as its dynamics during anti-HER2 treatment, is largely unknown. We here investigate changes in tumour-immune contexture, as assessed by stromal tumour-infiltrating lymphocytes (sTILs) and by multiplexed spatial cellular phenotyping, during treatment with lapatinib-trastuzumab in HER2+ BC patients (PAMELA trial). Moreover, we evaluate the relationship of tumour-immune contexture with hormone receptor status, intrinsic subtype and immune-related gene expression. sTIL levels increase after 2 weeks of HER2 blockade in HR-negative disease and HER2-enriched subtype. This is linked to a concomitant increase in cell density of all four immune subpopulations (CD3 + , CD4 + , CD8 + , Foxp3 + ). Moreover, immune contexture analysis showed that immune cells spatially interacting with tumour cells have the strongest association with response to anti-HER2 treatment. Subsequently, sTILs consistently decrease at the surgery in patients achieving pathologic complete response, whereas most residual tumours at surgery remain inflamed, possibly reflecting a progressive loss of function of T cells. Understanding the features of the resulting tumour immunosuppressive microenvironment has crucial implications for the design of new strategies to de-escalate or escalate systemic therapy in early-stage HER2+ BC.

Cardiovascular complications are important causes of morbidity and mortality of Type 1 Diabetes Mellitus (T1DM) people. Regular exercise is strongly recommended to these patients due to its preventive action against this type of disease. However, a large percentage of patients with T1DM people present a sedentary behavior, mainly, because of the fear of a post-exercise hypoglycemia event and lack of time. High-intensity interval training (HIIT) is an efficient and safe methodology since it prevents hypoglycemia and does not require much time, which are the main barriers for this population to doing exercise and increasing physical conditioning. Nineteen sedentary adults (37 ± 6.5 years) with T1DM were randomly assigned to 6 weeks of either HIIT, 12 bouts first 2 weeks, 16 bouts in weeks 3 and 4, and 20 bouts in the last two weeks x 30-s intervals interspersed with 1-min rest periods, performed thrice weekly or to control group, which did not train. VO 2max , body composition, heart rate variability (HRV), and fasting glucose were measured as cardiovascular risk factors. We suggest that the 6-week HIIT program used in the present study is safe since no severe hypoglycemia was reported and is an effective strategy in improving VO 2 max, body composition, HRV, and fasting glucose, which are important cardiovascular risk factors in T1DM people.

The full UHPLC-MS metabolome fingerprinting and anti- Helicobacter pylori effect of Gunnera tinctoria (Molina) Mirb. (Nalca) total extract (GTE) and fractions prepared from its edible fresh petioles were evaluated. The activity of G. tinctoria against H. pylori strains ATCC 45504 and J99 was assessed in vitro by means of agar diffusion assay, Minimum Inhibition Concentration (MIC), and Minimum Bactericidal Concentration (MBC), while killing curve and transmission electronic microscopy (TEM) were conducted in order to determine the effect of the plant extract on bacterial growth and ultrastructure. Additionally, the inhibitory effect upon urease was evaluated using both the Jack Bean and H. pylori enzymes. To determine which molecules could be responsible for the antibacterial effects, tentative identification was done by ultra-high performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-Q-Orbitrap®-HR-MS). Furthermore, the total G. tinctoria extract was fractionated using centrifugal partition chromatography (CPC), giving four active fractions (1-4). It was determined that the crude extract and centrifugal partition chromatography fractions of G. tinctoria have a bactericidal effect being the lowest MIC and MBC = 32 μg/ml. In the killing curves, fraction one acts faster than control amoxicillin. In the urease assay, F3 exhibited the lowest IC 50 value of 13.5 μg/ml. Transmission electronic microscopy showed that crude G. tinctoria extract promotes disruption and separation of the cellular wall and outer membrane detachment on H. pylori causing bacterial cell death., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hebel-Gerber, García-Cancino, Urbina, Simirgiotis, Echeverría, Bustamante-Salazar, Sáez-Carrillo, Alarcón and Pastene-Navarrete.)

People experiencing homelessness suffer from a risk of mortality three to four times that of the general population, with drug-induced overdose replacing HIV as the emerging epidemic. This study assessed markers of mortality among people experiencing homelessness (N=157) in Orange County, CA during the Fall of 2016. We utilized the Vulnerability Index, an eight-question survey, to identify factors that may affect mortality risk among individuals experiencing homelessness and included two additional questions to identify potential risk of drug-induced overdose. Eighty-three percent of participants reported more than one heightened mortality risk marker and 64% may be at higher risk of drug-induced overdose. Given the state of the opioid epidemic, there is pressing need to couple public health interventions targeting people experiencing homelessness with harm reduction efforts including naloxone distribution (opioid-induced overdose reversal medication) and syringe exchange programs.

Alzheimer's disease (AD) is a chronic, progressive, and fatal neurodegenerative disorder affecting cognition, behavior, and function, being one of the most common causes of mental deterioration in elderly people. Once thought as being just developed because of β amyloid depositions or neurofibrillary Tau tangles, during the last decades, numerous AD-related targets have been established, the multifactorial nature of AD became evident. In this context, the one drug-one target paradigm has resulted in being inefficient in facing AD and other disorders with complex etiology, opening the field for the emergence of the multitarget approach. In this review, we highlight the recent advances within this area, emphasizing in hybridization tools of well-known chemical scaffolds endowed with pharmacological properties concerning AD, such as curcumin-, resveratrol-, chromone- and indole-. We focus mainly on well established and incipient AD therapeutic targets, AChE, BuChE, MAOs, β-amyloid deposition, 5-HT4 and Serotonin transporter, with the aim to shed light about new insights in the AD multitarget therapy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Avocado Hass ( Persea americana Mill) peel extract (APE) has the potential as a natural ingredient to substitute for chemical preservatives. The objectives of this study were to assess the phytochemical composition by high-performance liquid chromatography-quadrupole time-of-flight mass/mass spectrometry (HPLC-qTOF-MS/MS), total phenolic content (TPC), proanthocyanidin (PAC) content, and antioxidant activity of the APE, the organic fraction (OF), the aqueous fraction (AF), and the acid-microwave hydrolyzed APE (HAPE), on the antibacterial activity (ABA). The results indicated that APE and OF contained ( p ˂ 0.05) a higher phenolic composition and antioxidant activity than AF and HAPE. The ABA specified that Pseudomonas aeruginosa and Bacillus cereus were inhibited by all the extracts (minimal inhibitory concentration-MIC ≥ 500 µg/mL), Staphylococcus aureus was only significantly inhibited by APE (≥750 µg/mL), the same MIC was observed for the OF on Salmonella spp. and Listeria monocytogenes . The HAPE increased the inhibitory efficiency up to 25% on Escherichia coli and Salmonella spp. (MIC ≥ 750 µg/mL), and 83.34% on L. monocytogenes (MIC ≥ 125 µg/mL) compared to APE (MIC ≥ 750 µg/mL). Also, HAPE inhibited the biofilm formation at the lowest concentration (125 µg/mL); meanwhile, the biofilm disruption showed to be concentration-time-dependent ( p ˃ 0.05) compared to amoxicillin. In conclusion, the fractionation and hydrolyzation of APE improved the ABA; thus, those strategies are useful to design new antimicrobial compounds.

Background: Type 1 diabetes mellitus (T1DM) is commonly associated with premature loss of muscle function, ankle dorsiflexion and dynamic balance. Those impairments, usually, lead to physical functionality deterioration. High-intensity interval training is an efficient and safety methodology since it prevents hypoglycemia and not requires much time, which are the main barriers for this population to practice exercise and increase physical conditioning. We hypothesized that a 6-week HIIT program performed on a cycle ergometer would increase lower limb muscle power, ankle dorsiflexion range of motion and dynamic balance without hypoglycemic situations., Methods: A total of 19 diagnosed T1DM subjects were randomly assigned to HIIT group ( n = 11; 6-week HIIT protocol) or Control group ( n = 8; no treatment). Lower limb strength was evaluated through velocity execution in squat with three different overloads. Weight bearing lunge test (WBLT) was performed to test ankle dorsiflexion range of motion and Y-Balance test (YBT) was the test conducted to analyze dynamic balance performance., Results: Velocity in squat improved a 11.3%, 9.4% and 10.1% ( p < 0.05) with the 50%, 60% and 70% of their own body mass overload respectively, WBLT performance increased a 10.43% in the right limb and 15.45% in the left limb. YBT showed improvements in all directions (right limb-left limb): Anterior (4.3-6.1%), Posteromedial (1.8-5.2%) and Posterolateral (3.4-4.5%) in HIIT group ( p < 0.05), unlike control group that did not experience any significant change in any of the variables ( p > 0.05)., Conclusion: A 6-week HIIT program is safe and effective to improve execution velocity in squat movement, a fundamental skill in daily living activities, as well as ankle dorsiflexion range of motion and dynamic balance to reduce foot ulcers, risk falls and functional impairments. HIIT seems an efficient and safety training methodology not only for overcome T1DM barriers for exercising but also for improving functional capacities in T1DM people., Competing Interests: The authors declare that they have no competing interests., (© 2020 Alarcón-Gómez et al.)

The ISAV has a genome composed of eight segments of (-)ssRNA, segment 6 codes for the hemagglutinin-esterase protein, and has the most variable region of the genome, the highly polymorphic region (HPR), which is unique among orthomyxoviruses. The HPR has been associated with virulence, infectivity and pathogenicity. The full length of the HPR is called HPR0 and the strain with this HPR is avirulent, in contrast to strains with deleted HPR that are virulent to varying degrees. The molecular mechanism that gives rise to the different HPRs remains unclear. Here, we studied in vitro the evolution of reassortant recombinant ISAV (rISAV) in Atlantic salmon head kidney (ASK) cells. To this end, we rescued and cultivated a set of rISAV with different segment 6-HPR genotypes using a reverse genetics system and then sequencing HPR regions of the viruses. Our results show rapid multiple recombination events in ISAV, with sequence insertions and deletions in the HPR, indicating a dynamic process. Inserted sequences can be found in four segments of the ISAV genome (segments 1, 5, 6, and 8). The results suggest intra-segmental heterologous recombination, probably by class I and class II template switching, similar to the proposed segment 5 recombination mechanism., (© 2020 John Wiley & Sons Ltd.)

The Chilean plants Discaria chacaye , Talguenea quinquenervia (Rhamnaceae), Peumus boldus (Monimiaceae), and Cryptocarya alba (Lauraceae) were evaluated against Codling moth: Cydia pomonella L. (Lepidoptera: Tortricidae) and fruit fly Drosophila melanogaster (Diptera: Drosophilidae), which is one of the most widespread and destructive primary pests of Prunus (plums, cherries, peaches, nectarines, apricots, almonds), pear, walnuts, and chestnuts, among other. Four benzylisoquinoline alkaloids (coclaurine, laurolitsine, boldine, and pukateine) were isolated from the above mentioned plant species and evaluated regarding their insecticidal activity against the codling moth and fruit fly. The results showed that these alkaloids possess acute and chronic insecticidal effects. The most relevant effect was observed at 10 µg/mL against D. melanogaster and at 50 µg/mL against C. pomonella , being the alteration of the feeding, deformations, failure in the displacement of the larvae in the feeding medium of D. melanogaster , and mortality visible effects. In addition, the docking results show that these type of alkaloids present a good interaction with octopamine and ecdysone receptor showing a possible action mechanism.

Background: In early-stage HER2-positive breast cancer, escalation or de-escalation of systemic therapy is a controversial topic. As an aid to treatment decisions, we aimed to develop a prognostic assay that integrates multiple data types for predicting survival outcome in patients with newly diagnosed HER2-positive breast cancer., Methods: We derived a combined prognostic model using retrospective clinical-pathological data on stromal tumour-infiltrating lymphocytes, PAM50 subtypes, and expression of 55 genes obtained from patients who participated in the Short-HER phase 3 trial. The trial enrolled patients with newly diagnosed, node-positive, HER2-positive breast cancer or, if node negative, with at least one risk factor (ie, tumour size >2 cm, histological grade 3, lymphovascular invasion, Ki67 >20%, age ≤35 years, or hormone receptor negativity), and randomly assigned them to adjuvant anthracycline plus taxane-based combinations with either 9 weeks or 1 year of trastuzumab. Trastuzumab was administered intravenously every 3 weeks (8 mg/kg loading dose at first cycle, and 6 mg/kg thereafter) for 18 doses or weekly (4 mg/kg loading dose in the first week, and 2 mg/kg thereafter) for 9 weeks, starting concomitantly with the first taxane dose. Median follow-up was 91·4 months (IQR 75·1-105·6). The primary objective of our study was to derive and evaluate a combined prognostic score associated with distant metastasis-free survival (the time between randomisation and distant recurrence or death before recurrence), an exploratory endpoint in Short-HER. Patient samples in the training dataset were split into a training set (n=290) and a testing set (n=145), balancing for event and treatment group. The training set was further stratified into 100 iterations of Monte-Carlo cross validation (MCCV). Cox proportional hazard models were fit to MCCV training samples using Elastic-Net. A maximum of 92 features were assessed. The final prognostic model was evaluated in an independent combined dataset of 267 patients with early-stage HER2-positive breast cancer treated with different neoadjuvant and adjuvant anti-HER2-based combinations and from four other studies (PAMELA, CHER-LOB, Hospital Clinic, and Padova) with disease-free survival outcome data., Findings: From Short-HER, data from 435 (35%) of 1254 patients for tumour size (T1 vs rest), nodal status (N0 vs rest), number of tumour-infiltrating lymphocytes (continuous variable), subtype (HER2-enriched and basal-like vs rest), and 13 genes composed the final model (named HER2DX). HER2DX was significantly associated with distant metastasis-free survival as a continuous variable (p<0·0001). HER2DX median score for quartiles 1-2 was identified as the cutoff to identify low-risk patients; and the score that distinguished quartile 3 from quartile 4 was the cutoff to distinguish medium-risk and high-risk populations. The 5-year distant metastasis-free survival of the low-risk, medium-risk, and high-risk populations were 98·1% (95% CI 96·3-99·9), 88·9% (83·2-95·0), and 73·9% (66·0-82·7), respectively (low-risk vs high-risk hazard ratio [HR] 0·04, 95% CI 0·0-0·1, p<0·0001). In the evaluation cohort, HER2DX was significantly associated with disease-free survival as a continuous variable (HR 2·77, 95% CI 1·4-5·6, p=0·0040) and as group categories (low-risk vs high-risk HR 0·27, 0·1-0·7, p=0·005). 5-year disease-free survival in the HER2DX low-risk group was 93·5% (89·0-98·3%) and in the high-risk group was 81·1% (71·5-92·1)., Interpretation: The HER2DX combined prognostic score identifies patients with early-stage, HER2-positive breast cancer who might be candidates for escalated or de-escalated systemic treatment. Future clinical validation of HER2DX seems warranted to establish its use in different scenarios, especially in the neoadjuvant setting., Funding: Instituto Salud Carlos III, Save the Mama, Pas a Pas, Fundación Científica, Asociación Española Contra el Cáncer, Fundación SEOM, National Institutes of Health, Agenzia Italiana del Farmaco, International Agency for Research on Cancer, and the Veneto Institute of Oncology, and Italian Association for Cancer Research., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

A series of 27 compounds of general structure 2,3-dihydro-benzo[1,4]oxazin-4-yl)-2-{4-[3-(1 H -3indolyl)-propyl]-1-piperazinyl}-ethanamides, Series I: 7 ( a - o ) and (2-{4-[3-(1 H -3-indolyl)-propyl]-1-piperazinyl}-acetylamine)- N -(2-morfolin-4-yl-ethyl)-fluorinated benzamides Series II: 13 ( a - l ) were synthesized and evaluated as novel multitarget ligands towards dopamine D 2 receptor, serotonin transporter (SERT), and monoamine oxidase-A (MAO-A) directed to the management of major depressive disorder (MDD). All the assayed compounds showed affinity for SERT in the nanomolar range, with five of them displaying K i values from 5 to 10 nM. Compounds 7k , K i = 5.63 ± 0.82 nM, and 13c , K i = 6.85 ± 0.19 nM, showed the highest potencies. The affinities for D 2 ranged from micro to nanomolar, while MAO-A inhibition was more discrete. Nevertheless, compounds 7m and 7n showed affinities for the D 2 receptor in the nanomolar range ( 7n : K i = 307 ± 6 nM and 7m : K i = 593 ± 62 nM). Compound 7n was the only derivative displaying comparable affinities for SERT and D 2 receptor (D 2 /SERT ratio = 3.6) and could be considered as a multitarget lead for further optimization. In addition, docking studies aimed to rationalize the molecular interactions and binding modes of the designed compounds in the most relevant protein targets were carried out. Furthermore, in order to obtain information on the structure-activity relationship of the synthesized series, a 3-D-QSAR CoMFA and CoMSIA study was conducted and validated internally and externally (q 2 = 0.625, 0.523 for CoMFA and CoMSIA and r 2 ncv = 0.967, 0.959 for CoMFA and CoMSIA, respectively).

Purpose: Multi-site musculoskeletal pain (MP) is common among health care professionals and is considered a threat to work ability and thereby a long and healthy working life. However, literature is scarce regarding these associations among physical therapists (PTs). This study aims to quantify the prevalence of local and multi-site MP among PTs, to investigate the associations between pain intensity and number of pain sites, respectively, with the level of work ability., Methods: We conducted a survey among 1006 PTs about pain the previous month in different body areas and work ability. Work ability was measured using the Work Ability Index (WAI) including its seven categories. The odds of having lower level of work ability as a function of pain intensity (0-10) and multi-site pain were determined using binary logistic regression controlled for relevant confounders., Results: The neck (36.3%) and the low back (32.3%) were the most commonly affected body areas. Furthermore, a dose-response relationship was observed between the number of pain sites and lower work ability (trend test, p < 0.001). With low pain intensity as reference, a moderate to strong association existed for lower levels of work ability in PTs who reported pain intensity of > 5 in one to two body regions (OR 2.14, 95% CI 1.27-3.60). This association was stronger when participants reported pain in three to four sites (OR 4.02, 95% CI 2.36-6.82) and even stronger when pain was experienced in five or more sites (OR 6.13, 95% CI 3.31-11.38)., Conclusions: Multi-site MP is strongly associated-in a dose-response fashion-with lower levels of work ability among PTs.