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Background: In the FLIPPER trial, palbociclib/fulvestrant significantly improved progression-free survival (PFS) compared with placebo/fulvestrant in postmenopausal women with HR+/HER2- advanced breast cancer (ABC)., Objective: We assessed health-related quality of life (QoL) using patient-reported outcomes (PROs)., Design and Methods: In this phase II double-blinded study, PROs were assessed at baseline after every three cycles and at the end of the treatment using the European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-BR23. Time to deterioration (TTD) in global health status (GHS)/QoL was defined as a decrease of ⩾10 points. Changes from baseline (CFB) and TTD were analysed using linear mixed-effect and Cox regression models, respectively., Results: Of the 189 randomised (1:1) patients, 178 (94%) completed ⩾1 post-baseline assessment; 50% received ⩾22 cycles of study treatment, with a questionnaire compliance >90%. Mean baseline scores were comparable between arms. GHS/QoL scores were maintained throughout the palbociclib/fulvestrant treatment. CFB showed significant differences for GHS/QoL, appetite loss, constipation and systemic therapy side effect scores favouring placebo/fulvestrant. TTD in GHS/QoL was delayed in placebo/fulvestrant versus palbociclib/fulvestrant [30.3 versus 11.1 months; adjusted hazard ratio (aHR): 1.57, 95% CI: 1.03-2.39, p  = 0.036]; this difference was not significant in patients with progressive disease (aHR: 1.2, 95% CI: 0.6-2.2, p  = 0.658). No statistically significant differences in TTD were found for the other QLQ-C30 and QLQ-BR23 scales., Conclusions: Although TTD in GHS/QoL was prolonged with placebo/fulvestrant, no differences were observed on other functional or symptom scales. This finding and the improvement in PFS support the combination of palbociclib/fulvestrant as a beneficial therapeutic option for HR+/HER2- ABC., Trial Registration Number: Sponsor Study Code: GEICAM/2014-12EudraCT Number: 2015-002437-21ClinTrials.gov reference: NCT02690480., Competing Interests: Dr. Tibau has received speaker fees from Novartis and Eisai. Dr. Ramos has received speaker’s bureau from Novartis, Pfizer and Roche Farma. Dr. de La Cruz-Merino has received advisory board fees from MSD-Merk, Roche Farma, Bristol-Myers-Squibb, Pierre-Fabré, Amgen and Novartis; research funding from MSD-Merck, Roche Farma, Celgene; speaking fees from MSD-Merck, Roche Farma, Bristol-Myers-Squibb and Amgen; grant support from Bristol-Myers-Squibb and Roche Farma. Dr. 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. Dr. Martínez-Jañez has received advisory board fees from Roche Farma, Astra Zeneca, Pfizer, Novartis, Lilly, Daiichi Sankyo, Agendia and Eisai. Dr. Moreno has received advisory board fees from Roche/Genentech, Novartis, Pfizer, AstraZeneca, MSD-Merck and Daiichi Sankyo/AstraZeneca; speaker’s bureau fees from Pfizer; travel accommodations expenses from Roche/Genentech, Pfizer, Novartis, Daiichi Sankyo/Astra Zeneca. Dr. Fernández has received consultant or advisory fees from MSD-Astra Zeneca; speaker’s bureau fees from Pfizer, AstraZeneca, Roche, MSD, Clovis and GSK. Dr. Alarcón: has received honoraria from GSC, Clovis, Roche and AstraZeneca; consulting or advisory board honoraria from GSK and Clovis; speaker and expert testimony fees from GSK, Clovis and Roche; and travel and accommodation support from GSK. Dr. de La Haba-Rodríguez has received speaker’s honoraria from AstraZeneca, Pfizer, Novartis and Lilly. Dr. Sánchez-Rovira has received honoraria from Novartis, Lilly, Pfizer, Roche and Seagen. Dr. Bueno Muiño has received speaker fees from Novartis, Lilly, AstraZeneca, BMS, Pfizer and GSK. Dr. 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. All remaining authors have declared no conflicts of interest. GEICAM has received research funding from Roche/Genentech, Bristol-Myers Squibb, Novartis, Pfizer, Celgene, AstraZeneca, Merck Sharp & Dohme, Pierre Fabre and Takeda. A complete list of the FLIPPER trial collaborators is provided in the Supplemental Appendix., (© The Author(s), 2023.)

Parkinson's disease (PD) is a neurodegenerative disorder that results from the degeneration of dopaminergic neurons in the substantia nigra pars compacta ( SNpc ). Since there are only symptomatic treatments available, new cellular and molecular targets involved in the onset and progression of this disease are needed to develop effective treatments. CCAAT/Enhancer Binding Protein β (C/EBPβ) transcription factor levels are altered in patients with a variety of neurodegenerative diseases, suggesting that it may be a good therapeutic target for the treatment of PD. A list of genes involved in PD that can be regulated by C/EBPβ was generated by the combination of genetic and in silico data, the mitochondrial transcription factor A (TFAM) being among them. In this paper, we observed that C/EBPβ overexpression increased TFAM promoter activity. However, downregulation of C/EBPβ in different PD/neuroinflammation cellular models produced an increase in TFAM levels, together with other mitochondrial markers. This led us to propose an accumulation of non-functional mitochondria possibly due to the alteration of their autophagic degradation in the absence of C/EBPβ. Then, we concluded that C/EBPβ is not only involved in harmful processes occurring in PD, such as inflammation, but is also implicated in mitochondrial function and autophagy in PD-like conditions.

In order to find molecules of natural origin with potential biological activities, we isolate and synthesise compounds with agarofuran skeletons (epoxyeudesmanes). From the seeds of Maytenus disticha and Maytenus magellanica we obtained six dihydro-β-agarofurans, and by means of the Robinson annulation reaction we synthesised five compounds with the same skeleton. The structures were established on the basis of NMR, IR, and MS. The evaluated compounds showed inhibitory activity on the acetylcholinesterase enzyme and on the COX enzymes. Compound 4 emerged as the most potent in the acetylcholinesterase inhibition assay with IC 50 17.0 ± 0.016 µM on acetylcholinesterase (AChE). The compounds evaluated were shown to be selective for AChE. The molecular docking, and the propidium displacement assay suggested that the compounds do not bind to the active site of the enzyme AChE, but rather bind to the peripheral anionic site (PAS) of the enzyme, on the other hand, the natural compound 8 , showed the best inhibitory activity on the COX-2 enzyme with an IC 50 value of 0.04 ± 0.007 µM. The pharmacokinetic profile calculated in silico using the SWISSADME platform shows that these molecules could be considered as potential drugs for the treatment of neurodegenerative diseases such as AD.

Introduction: The COVID-19 pandemic is still in force, causing global public health challenges and threats. Although vaccination and herd immunity have proven to be the most efficient way to control the pandemic, massive and early testing of patients using the RT-qPCR technique is crucial for constant genomic surveillance. The appearance of variants of SARS-CoV-2 with new mutations can reduce the efficiency of diagnostic detection. In this sense, several commercial RT-qPCR kits have been the target of extensive analysis because low assay performance could lead to false-negative diagnoses., Methods: In this study, we evaluated the performance of three commercial RT-qPCR kits; Thermo Fisher (TaqMan 2019-nCoV Assay Kit v1), BGI and Roche (LightCycler ® Multiplex RNA Virus Master) used for the diagnosis of COVID-19 throughout the pandemic in Santiago de Chile., Results: Under our best assay conditions, we found significant differences in Cq amplification values for control and viral probes, against the same nasopharyngeal swab samples (NPSs). In addition, in some cases, the sensitivity of the RT-qPCR kits decreased against viral variants., Conclusion: Our study suggests evaluating the RT-qPCR kits used to detect SARS-CoV-2 because variants such as Omicron, which has several mutations, can compromise their detection and underestimate viral circulation., 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 Luraschi, Santibáñez, Barrera-Avalos, Vallejos-Vidal, Mateluna-Flores, Alarcón, Cayunao, Mella-Torres, Hernández, Inostroza-Molina, Valdés, Imarai, Acuña-Castillo, Reyes-López and Sandino.)

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative and fatal disease, characterized by the loss of motor neurons and progressive musculoskeletal deterioration. The clinical onset is mainly bulbar or spinal. Considering that there is no effective medical treatment, there is a need to understand the muscle activation patterns to design better physical exercise routines. The objective of this study was to determine muscle strength and fatigue in patients with ALS performing a unilateral exercise, and according to sex and type of ALS. A cross-sectional, analytical study was conducted with 23 patients. Five maximal unilateral isometric contractions were performed with the right and left biceps brachii. Muscle activation was calculated by surface electromyography bilaterally in the biceps brachii, triceps brachii, rectus femoris anterior, and tibialis anterior. The results showed more accentuated fatigue in men than in women, between the first and last contractions performed and especially on the dominant side ( p = 0.016). In addition, there was evidence of a coactivation effect on the muscles around the work joint, which reflects a growing activation of synergists, regardless of sex or type of ALS. These findings support the use of systematic and extensive resistance exercise as a non-invasive option for maintaining the functional capacity of patients with ALS.

Background: Rucaparib is a poly(ADP-ribose) polymerase inhibitor approved in Europe as maintenance therapy for recurrent platinum-sensitive (Pt-S) ovarian cancer (OC). The Rucaparib Access Programme (RAP) was designed to provide early access to rucaparib for the above-mentioned indication, as well as for patients with BRCA-mutated Pt-S or platinum-resistant (Pt-R) OC and no therapeutic alternatives., Methods: In this observational, retrospective study we analysed the efficacy and safety of rucaparib within the RAP in Spain. Hospitals associated with the Spanish Ovarian Cancer Research Group (GEICO) recruited patients with high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer treated with rucaparib 600 mg twice daily as maintenance or treatment (Pt-S/Pt-R) in the RAP. Baseline characteristics, efficacy, and safety data were collected., Results: Between July 2020 and February 2021, 51 patients treated in 22 hospitals in the RAP were included in the study. Eighteen patients with a median of 3 (range, 1-6) prior treatment lines received rucaparib as maintenance; median progression-free survival (PFS) for this group was 9.1 months (95% confidence interval [CI], 4.2-11.6 months). Among 33 patients (median 5 [range, 1-9] prior treatment lines) who received rucaparib as treatment, 7 and 26 patients had Pt-S and Pt-R disease, respectively. Median PFS was 10.6 months (95% CI, 2.5 months-not reached) in the Pt-S group and 2.2 months (95% CI, 1.1-3.2 months) in the Pt-R group. Grade ≥ 3 treatment-emergent adverse events were reported in 39% of all patients, the most common being anaemia (12% and 15% in the maintenance and treatment groups, respectively). At data cut-off, 5 patients remained on treatment., Conclusion: Efficacy results in these heavily pre-treated patients were similar to those from previous trials. The safety profile of rucaparib in real life was predictable and manageable., (© 2022. The Author(s).)

Data on monkeypox in children and adolescents aged <18 years are limited (1,2). During May 17–September 24, 2022, a total of 25,038 monkeypox cases were reported in the United States, † primarily among adult gay, bisexual, and other men who have sex with men (3). During this period, CDC and U.S. jurisdictional health departments identified Monkeypox virus (MPXV) infections in 83 persons aged <18 years, accounting for 0.3% of reported cases. Among 28 children aged 0–12 years with monkeypox, 64% were boys, and most had direct skin-to-skin contact with an adult with monkeypox who was caring for the child in a household setting. Among 55 adolescents aged 13–17 years, most were male (89%), and male-to-male sexual contact was the most common presumed exposure route (66%). Most children and adolescents with monkeypox were non-Hispanic Black or African American (Black) (47%) or Hispanic or Latino (Hispanic) (35%). Most (89%) were not hospitalized, none received intensive care unit (ICU)–level care, and none died. Monkeypox in children and adolescents remains rare in the United States. Ensuring equitable access to monkeypox vaccination, testing, and treatment is a critical public health priority. Vaccination for adolescents with risk factors and provision of prevention information for persons with monkeypox caring for children might prevent additional infections., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

As of October 21, 2022, a total of 27,884 monkeypox cases (confirmed and probable) have been reported in the United States. § Gay, bisexual, and other men who have sex with men have constituted a majority of cases, and persons with HIV infection and those from racial and ethnic minority groups have been disproportionately affected (1,2). During previous monkeypox outbreaks, severe manifestations of disease and poor outcomes have been reported among persons with HIV infection, particularly those with AIDS (3-5). This report summarizes findings from CDC clinical consultations provided for 57 patients aged ≥18 years who were hospitalized with severe manifestations of monkeypox ¶ during August 10-October 10, 2022, and highlights three clinically representative cases. Overall, 47 (82%) patients had HIV infection, four (9%) of whom were receiving antiretroviral therapy (ART) before monkeypox diagnosis. Most patients were male (95%) and 68% were non-Hispanic Black (Black). Overall, 17 (30%) patients received intensive care unit (ICU)-level care, and 12 (21%) have died. As of this report, monkeypox was a cause of death or contributing factor in five of these deaths; six deaths remain under investigation to determine whether monkeypox was a causal or contributing factor; and in one death, monkeypox was not a cause or contributing factor.** Health care providers and public health professionals should be aware that severe morbidity and mortality associated with monkeypox have been observed during the current outbreak in the United States (6,7), particularly among highly immunocompromised persons. Providers should test all sexually active patients with suspected monkeypox for HIV at the time of monkeypox testing unless a patient is already known to have HIV infection. Providers should consider early commencement and extended duration of monkeypox-directed therapy †† in highly immunocompromised patients with suspected or laboratory-diagnosed monkeypox. §§ Engaging all persons with HIV in sustained care remains a critical public health priority., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Siobhán M. O’Connor reports US Patent Application #20190212345 and #20150140670 for kits and methods for determining physiologic levels and ranges of hemoglobin or disease state. Nicola A. Hanania reports institutional support from GSK, Sanofi, Genentech, AstraZeneca, and Teva; consulting fees from AstraZeneca, GSK, Boehringer Ingelheim, Sanofi, Genentech, Teva, and Amgen; and service as editor in chief of Respiratory Medicine. Jerry Clay Goodman reports payment from the American Academy of Neurology for a course in neuropathology at the annual meeting. No other potential conflicts of interest were disclosed.

Crop wild relatives (CWR) intra- and interspecific diversity is essential for crop breeding and food security. However, intraspecific genetic diversity, which is central given the idiosyncratic threats to species in landscapes, is usually not considered in planning frameworks. Here, we introduce an approach to develop proxies of genetic differentiation to identify conservation areas, applying systematic conservation planning tools that produce hierarchical prioritizations of the landscape. It accounts for: (i) evolutionary processes, including historical and environmental drivers of genetic diversity, and (ii) threat processes, considering taxa-specific tolerance to human-modified habitats, and their extinction risk status. Our analyses can be used as inputs for developing national action plans for the conservation and use of CWR. Our results also inform public policy to mitigate threat processes to CWR (like crops living modified organisms or agriculture subsidies), and could advise future research (e.g. for potential germplasm collecting). Although we focus on Mesoamerican CWR within Mexico, our methodology offers opportunities to effectively guide conservation and monitoring strategies to safeguard the evolutionary resilience of any taxa, including in regions of complex evolutionary histories and mosaic landscapes., (© 2022. The Author(s).)

The mouth opening is an important indication of the functionality of the temporomandibular joint (TMJ). Mouth opening is usually evaluated by asking the patient to open their mouth as wide as possible and measuring the distance between the edges of the frontal incisors with a ruler or caliper. With the advancement of technology, new techniques have been proposed to record mandibular movement. The aim of this work is to present a novel technique based on 3D electromagnetic articulography and data postprocessing to analyze the mouth opening considering distances, trajectories, and angles. A maxilla-mandible phantom was used to simulate the mouth opening movement and fixed position mouth opening. This was recorded using the AG501 3D EMA (Carstens Medizinelektronik GmbH, Bovenden, Germany). The collected data was processed using Matlab (Mathworks, Natick, MA, USA). Fix and mobile mouth opening of 1, 2, 3 and 4 cm were simulated. It was possible to evaluate the mandibular opening through the vertical distance, the Euclidean distance, the trajectory, and the opening angle. All these values were calculated and the results were consistent with expectations. The trajectory was the highest value obtained while the vertical distance was the lowest. The angle increased as the mouth opening increased. This new technique opens up new possibilities in future research since oral opening can be analyzed using multiple variables without the need to use different devices or depending on the researcher's experience. This will make it possible to establish which parameter presents significant differences between groups of patients or between patients who have undergone some treatment.

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.)

Mesiodens are the most common supernumerary teeth and are detected incidentally during routine radiographic examination, so late diagnosis complications are very common. The dentist must make a timely diagnosis and thus avoid clinical complications. Despite advances in knowledge of dental morphogenesis and differentiation, the etiology of mesiodens remains unclear. Therefore, several theories have been postulated to explain how and why they develop. It was described in the literature that heredity could play an important role in the appearance of supernumerary teeth, with a higher rate of appearance in relatives of those affected. This article reports three cases, a mother and two children, who present mesiodens, which shows that supernumerary teeth may involve a genetic factor. In addition, a literature review was carried out to assess the importance of the genetic factor as a possible cause of mesiodens. The relevance and implications of timely diagnosis in clinical practice to avoid manifestations of clinical complications are discussed. Therefore, the identification of the genetic risk factors responsible for the formation of supernumerary teeth is essential for developing a screening tool to determine an individual's genetic risk.

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.)

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.)

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.)

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.)

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.

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., (© 2021 SERAM. Published by 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.)

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.)

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.)