Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 86
Filter
1.
Rev. biol. trop ; 71(1)dic. 2023.
Article in English | LILACS-Express | LILACS | ID: biblio-1449505

ABSTRACT

Introduction: Seed dispersal and seed predation have important impacts on plant diversity and community structure. Rodents participate in both of these types of interactions. Objectives: To evaluate the removal of the seeds of Crescentia alata, Randia capitata, and Zea mays by the squirrel Notocitellus adocetus to determine how it affects these plant species, by dispersing or preying on their seeds. Methods: We studied 14 individuals for C. alata, 24 for R. capitata, and for Z. mays 35 individuals. We observed foraging and used camera traps to determine the part of the fruit (seed and/or pulp) consumed by the squirrels and the amount of fruit or seed consumed. We also placed fine sand traps (FST) to measure the percentage of seed removal. We quantified the fruits produced by the plant species studied and the percentage of damage caused by N. adocetus throughout the plots. Results: Notocitellus adocetus feeds on the seeds and pulp of C. alata and Z. mays. The species with the highest removal rate and the highest percentage of damage was C. alata. Zea mays was the plant species that had the highest percentage of removal from FST, the largest number of fruits, and the lowest percentage of damage. On FST, R. capitata had the lowest seed remotion. Conclusions: Notocitellus adocetus is considered a seed predator; however, due to its behavior and the characteristics of the fruits of C. alata and R. capitata, this rodent could make the seeds available to secondary seed dispersers.


Introducción: La dispersión y depredación de semillas tienen efectos importantes en la diversidad de plantas y estructura de las comunidades. Los roedores participan en estos tipos de interacciones. Objetivos: Evaluar la remoción de semillas de Crescentia alata, Randia capitata y Zea mays por la ardilla Notocitellus adocetus, para determinar su efecto en estas especies de plantas, dispersando o depredando semillas. Métodos: Estudiamos 14 individuos de C. alata, 24 para R. capitata y 35 individuos para Z. mays. Observamos el forrajeo y usamos cámaras trampas para determinar la parte del fruto (semilla y/o pulpa) consumida y la intensidad de consumo por las ardillas. También colocamos trampas de arena fina (FST) para medir el porcentaje de remoción de semillas. Cuantificamos los frutos producidos por las especies estudiadas y el porcentaje de daño ocasionado por N. adocetus, mediante parcelas. Resultados: Notocitellus adocetus se alimenta de las semillas y pulpa de C. alata y Z. mays. La especie que tuvo mayor tasa de remoción y mayor porcentaje de daño fue C. alata. La especie con mayor porcentaje de remoción, mayor número de frutos y menor daño en las FST fue Z. mays. En las trampas de arena fina, R. capitata tuvo la menor remoción de semillas. Conclusiones: Notocitellus adocetus es considerada depredadora de semillas, no obstante, por su comportamiento y las características de los frutos de C. alata y R. capitata, este roedor podría dejar disponibles las semillas a dispersores secundarios de semillas.

2.
Cureus ; 15(8): e43628, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37719633

ABSTRACT

Tumor immunotherapy is an important clinical strategy for the treatment of various solid and hematological malignancies, and its use is on the rise. Immune checkpoint inhibitors (ICIs) are immunotherapies that boost anticancer immune responses by targeting receptors on the surface of T-lymphocytes. Two important ICIs are anti-programmed death ligand-1 (anti-PD-L1) monoclonal antibodies and anti-cytotoxic T-lymphocyte-associated antigen-4 (anti-CTLA-4) monoclonal antibodies. Tremelimumab (anti-CTLA-4) and durvalumab (anti-PD-L1) have been shown to be effective monotherapies. However, their combination has demonstrated effective and encouraging antitumor activity with manageable safety in patients with unresectable hepatocellular carcinoma. We present the case of an 80-year-old male with hepatocellular carcinoma who had undergone drug-eluting bead transarterial chemoembolization (DEB-TACE) on three occasions and had been started on a combination of ICIs, durvalumab, and tremelimumab. He subsequently developed various immune-related adverse effects in different organ systems, including hepatic and cardiovascular complications. Appropriate treatment was administered, but ultimately, he passed away. We aim to discuss the initial evaluation for suspected immune-related adverse events, specifically those related to myocarditis and its various manifestations, prognosis, and treatment.

3.
Biomed Pharmacother ; 162: 114614, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37068330

ABSTRACT

The continuing heavy toll of the COVID-19 pandemic necessitates development of therapeutic options. We adopted structure-based drug repurposing to screen FDA-approved drugs for inhibitory effects against main protease enzyme (Mpro) substrate-binding pocket of SARS-CoV-2 for non-covalent and covalent binding. Top candidates were screened against infectious SARS-CoV-2 in a cell-based viral replication assay. Promising candidates included atovaquone, mebendazole, ouabain, dronedarone, and entacapone, although atovaquone and mebendazole were the only two candidates with IC50s that fall within their therapeutic plasma concentration. Additionally, we performed Mpro assays on the top hits, which demonstrated inhibition of Mpro by dronedarone (IC50 18 µM), mebendazole (IC50 19 µM) and entacapone (IC50 9 µM). Atovaquone showed only modest Mpro inhibition, and thus we explored other potential mechanisms. Although atovaquone is Dihydroorotate dehydrogenase (DHODH) inhibitor, we did not observe inhibition of DHODH at the respective SARS-CoV-2 IC50. Metabolomic profiling of atovaquone treated cells showed dysregulation of purine metabolism pathway metabolite, where ecto-5'-nucleotidase (NT5E) was downregulated by atovaquone at concentrations equivalent to its antiviral IC50. Atovaquone and mebendazole are promising candidates with SARS-CoV-2 antiviral activity. While mebendazole does appear to target Mpro, atovaquone may inhibit SARS-CoV-2 viral replication by targeting host purine metabolism.


Subject(s)
Antiviral Agents , COVID-19 , Humans , Antiviral Agents/pharmacology , SARS-CoV-2 , Dihydroorotate Dehydrogenase , Drug Repositioning , Dronedarone/pharmacology , Pandemics , Atovaquone/pharmacology , Mebendazole/pharmacology , Purines/pharmacology , Molecular Docking Simulation , Protease Inhibitors/pharmacology , Molecular Dynamics Simulation
4.
Sensors (Basel) ; 23(6)2023 Mar 16.
Article in English | MEDLINE | ID: mdl-36991888

ABSTRACT

Due to the edaphoclimatic conditions in southeast Spain, which are expected to worsen due to climate change, more efficient ways of using water must be found to maintain sustainable agriculture. Due to the current high price of irrigation control systems in southern Europe, 60-80% of soilless crops are still irrigated, based on the experience of the grower or advisor. The hypothesis of this work is that the development of a low-cost, high-performance control system will allow small farmers to improve the efficiency of water use by obtaining better control of soilless crops. The objective of the present study was to design and develop a cost-effective control system for the optimization of soilless crop irrigation after evaluating the three most commonly used irrigation control systems to determine the most efficient. Based on the agronomic results comparing these methods, a prototype of a commercial smart gravimetric tray was developed. The device records the irrigation and drainage volumes and drainage pH and EC. It also offers the possibility of determining the temperature, EC, and humidity of the substrate. This new design is scalable thanks to the use of an implemented data acquisition system called SDB and the development of software in the Codesys programming environment based on function blocks and variable structures. The reduced wiring achieved by the Modbus-RTU communication protocols means the system is cost-effective even with multiple control zones. It is also compatible with any type of fertigation controller through external activation. Its design and features solve the problems in similar systems available on the market at an affordable cost. The idea is to allow farmers to increase their productivity without having to make a large outlay. The impact of this work will make it possible for small-scale farmers to have access to affordable, state-of-the-art technology for soilless irrigation management leading to a considerable improvement in productivity.

5.
Cell Chem Biol ; 30(2): 214-229.e18, 2023 02 16.
Article in English | MEDLINE | ID: mdl-36758549

ABSTRACT

Glioblastoma (GBM) is an aggressive adult brain cancer with few treatment options due in part to the challenges of identifying brain-penetrant drugs. Here, we investigated the mechanism of MM0299, a tetracyclic dicarboximide with anti-glioblastoma activity. MM0299 inhibits lanosterol synthase (LSS) and diverts sterol flux away from cholesterol into a "shunt" pathway that culminates in 24(S),25-epoxycholesterol (EPC). EPC synthesis following MM0299 treatment is both necessary and sufficient to block the growth of mouse and human glioma stem-like cells by depleting cellular cholesterol. MM0299 exhibits superior selectivity for LSS over other sterol biosynthetic enzymes. Critical for its application in the brain, we report an MM0299 derivative that is orally bioavailable, brain-penetrant, and induces the production of EPC in orthotopic GBM tumors but not normal mouse brain. These studies have implications for the development of an LSS inhibitor to treat GBM or other neurologic indications.


Subject(s)
Glioblastoma , Glioma , Adult , Humans , Lanosterol/pharmacology , Lanosterol/metabolism , Brain/metabolism , Glioma/drug therapy , Glioma/metabolism , Cholesterol , Glioblastoma/drug therapy
7.
Foods ; 13(1)2023 Dec 19.
Article in English | MEDLINE | ID: mdl-38201032

ABSTRACT

The utilization of eco-innovative products has witnessed a surge in adoption, driven by their inherent capacity to address pressing environmental concerns. To comprehensively fathom the underlying motivations propelling consumers to embrace these products, we conducted an in-depth investigation employing "The Not Company" (Chile) as a compelling case study. We conducted qualitative interviews with a cohort of 20 Chilean consumers, guided by the Theory of Planned Behavior theoretical framework. The research methodology harnessed the principles of thematic analysis, yielding insights that underscore the significance of key determinants in shaping consumers' choices towards eco-innovative products. Specifically, our findings highlighted that consumer choices in this domain are profoundly influenced by their attitudes, subjective norms, and perceived behavioral control. Moreover, within these overarching categories, we unearthed sub-themes illuminating the intricate influences guiding consumer choices. These sub-themes encompassed beliefs about food manufacturing and packaging, the persuasive impact of social media and advertising, and the indelible impressions left by prior encounters with eco-innovative products. This study highlights consumers' fundamental role in the broader eco-innovation landscape, particularly within the food industry context.

8.
PLoS One ; 17(12): e0278275, 2022.
Article in English | MEDLINE | ID: mdl-36454740

ABSTRACT

OBJECTIVE: To construct an individual socioeconomic status index (ISESI) with information available in the Population Information System of the Region of Valencia, Spain, and use it to analyse inequalities in a colorectal cancer screening programme (CRCSP). METHODS: Cross-sectional study of men and women aged between 50 and 75 at the time of the study (2020) that were selected from the target population of the Region of Valencia CRCSP. (study sample 1,150,684). First, a multiple correspondence analysis was performed to aggregate information from the Population Information System of the Region of Valencia into an ISESI. Second, data from the 2016 Region of Valencia Health Survey were used for validation, and finally the relationship between CRCSP participation and the ISESI was analysed by logistic regression models. RESULTS: The variables included in the index were nationality, employment status, disability, healthcare coverage, risk of vulnerability and family size. The most important categories for determining the highest socioeconomic status were being employed and not being at risk of social vulnerability, and being unemployed and at risk of social vulnerability for determining the lowest socioeconomic status. Index validation demonstrated internal and external coherence for measuring socioeconomic status. The relationship between CRCSP participation and the ISESI categorised by quartile (Q) showed that Q4 (the lowest socioeconomic status) was less likely to participate OR = 0.769 (0.757-0.782) than Q1 (the highest socioeconomic status), and the opposite was found for Q2 OR = 1.368 (1.347-1.390) and Q3 OR = 1.156 (1.137-1.175). CONCLUSIONS: An ISESI was constructed and validated using Population Information System data and made it possible to evaluate inequalities in colorectal cancer screening.


Subject(s)
Colorectal Neoplasms , Early Detection of Cancer , Male , Female , Humans , Middle Aged , Aged , Cross-Sectional Studies , Social Class , Income , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/epidemiology
9.
Sensors (Basel) ; 22(20)2022 Oct 19.
Article in English | MEDLINE | ID: mdl-36298332

ABSTRACT

The increasing isolation of the elderly both in their own homes and in care homes has made the problem of caring for elderly people who live alone an urgent priority. This article presents a proposed design for a heterogeneous multirobot system consisting of (i) a small mobile robot to monitor the well-being of elderly people who live alone and suggest activities to keep them positive and active and (ii) a domestic mobile manipulating robot that helps to perform household tasks. The entire system is integrated in an automated home environment (AAL), which also includes a set of low-cost automation sensors, a medical monitoring bracelet and an Android application to propose emotional coaching activities to the person who lives alone. The heterogeneous system uses ROS, IoT technologies, such as Node-RED, and the Home Assistant Platform. Both platforms with the home automation system have been tested over a long period of time and integrated in a real test environment, with good results. The semantic segmentation of the navigation and planning environment in the mobile manipulator for navigation and movement in the manipulation area facilitated the tasks of the later planners. Results about the interactions of users with the applications are presented and the use of artificial intelligence to predict mood is discussed. The experiments support the conclusion that the assistance robot correctly proposes activities, such as calling a relative, exercising, etc., during the day, according to the user's detected emotional state, making this is an innovative proposal aimed at empowering the elderly so that they can be autonomous in their homes and have a good quality of life.


Subject(s)
Artificial Intelligence , Quality of Life , Humans , Aged , Home Environment , Reactive Oxygen Species , Monitoring, Physiologic
10.
Clin Neuropsychol ; 36(8): 2260-2277, 2022 11.
Article in English | MEDLINE | ID: mdl-34554056

ABSTRACT

Objective. Neuropsychological measures of processing speed have long been used as sensitive indices of cognitive functioning. Most of these commonly used tests are proprietary, and there is a need for brief, freely available tools that can be used in diverse clinical and research settings. The Southwestern Assessment of Processing Speed (SWAPS) is a 60-second digit-symbol transcription task developed as a brief alternative to commercially available coding tests. Demographically-corrected normative data are presented along with reliability and sensitivity/specificity values in older adults with and without cognitive impairment.Method. SWAPS data from 915 healthy aging individuals (NC) and 858 subjects with clinical diagnoses of mild cognitive impairment (MCI; n = 430) and Alzheimer's disease clinical syndrome (ADCS; n = 428) were obtained from the Texas Alzheimer's Research and Care Consortium (TARCC). TARCC participants represent ethnically and educationally diverse community-dwelling individuals age 50+.Results. SWAPS scores showed the expected associations with age, sex, and education, and the interaction between age and education were significant predictors of SWAPS scores. Test-retest reliability in NC was good, and the SWAPS distinguished impaired and non-impaired groups with adequate to excellent sensitivity and specificity for the primary analyses, with optimal cut-off points provided. Raw score- to uncorrected normalized T-scores and demographically-corrected SWAPS T-scores using regression-based norms are presented along with scoring programs for the calculation of each.Conclusions. The SWAPS is a brief, free, easily administered test with demographically-corrected regression-based norms and promising utility for detection of cognitive impairment and efficient assessment of processing speed.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Humans , Aged , Middle Aged , Neuropsychological Tests , Reproducibility of Results , Cognition , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/psychology , Alzheimer Disease/diagnosis , Alzheimer Disease/psychology
11.
Sensors (Basel) ; 21(20)2021 Oct 16.
Article in English | MEDLINE | ID: mdl-34696078

ABSTRACT

The increasingly ageing population and the tendency to live alone have led science and engineering researchers to search for health care solutions. In the COVID 19 pandemic, the elderly have been seriously affected in addition to suffering from isolation and its associated and psychological consequences. This paper provides an overview of the RobWell (Robotic-based Well-Being Monitoring and Coaching System for the Elderly in their Daily Activities) system. It is a system focused on the field of artificial intelligence for mood prediction and coaching. This paper presents a general overview of the initially proposed system as well as the preliminary results related to the home automation subsystem, autonomous robot navigation and mood estimation through machine learning prior to the final system integration, which will be discussed in future works. The main goal is to improve their mental well-being during their daily household activities. The system is composed of ambient intelligence with intelligent sensors, actuators and a robotic platform that interacts with the user. A test smart home system was set up in which the sensors, actuators and robotic platform were integrated and tested. For artificial intelligence applied to mood prediction, we used machine learning to classify several physiological signals into different moods. In robotics, it was concluded that the ROS autonomous navigation stack and its autodocking algorithm were not reliable enough for this task, while the robot's autonomy was sufficient. Semantic navigation, artificial intelligence and computer vision alternatives are being sought.


Subject(s)
COVID-19 , Mentoring , Robotics , Aged , Artificial Intelligence , Humans , SARS-CoV-2
12.
J Cosmet Dermatol ; 20(10): 3155-3164, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34460984

ABSTRACT

BACKGROUND: The portfolio of hyaluronic acid (HA) fillers and the techniques of administration have evolved in recent years. The latest innovation in the Vycross® range was the introduction of VYC-25L (Juvéderm Volux® ; Allergan plc), a first-in-class filler effective for chin and facial lower third remodeling. The aim here was to provide clinicians who are starting to use VYC-25L with key advice, and to standardize procedures so that optimal and predictable outcomes can be obtained. METHODS: A multidisciplinary group of experts in esthetic medicine from Spain and Portugal reviewed the properties, treatment paradigms, administration techniques, and potential complications of VYC-25L, on the basis of which they drafted consensus recommendations for its clinical use. RESULTS: The consensus panel provided specific recommendations focusing on the patient profile, dose, administration techniques, and the complications of VYC-25L and their management. The panel identified five different profiles of patients who may benefit from VYC-25L, and they drafted recommendations aimed to facilitate the treatment of these patients, namely, microgenia (women/men), masculinization (men), rejuvenation (women/men), facial laxity (women/men), and submental convexity (women/men). In terms of their safety, no specific recommendations were made beyond those established for other HA fillers. CONCLUSIONS: The evolution of esthetic medicine makes it necessary to update the clinical recommendations that guide patient assessment and treatment with the new HA fillers developed. The current consensus document addresses relevant issues related to the use of VYC-25L on different types of patient, in an attempt to standardize procedures and help specialists obtain predictable results.


Subject(s)
Cosmetic Techniques , Dermal Fillers , Skin Aging , Consensus , Dermal Fillers/adverse effects , Female , Humans , Hyaluronic Acid , Male , Treatment Outcome
13.
Cognit Comput ; : 1-12, 2021 Jun 03.
Article in English | MEDLINE | ID: mdl-34104256

ABSTRACT

To understand and approach the spread of the SARS-CoV-2 epidemic, machine learning offers fundamental tools. This study presents the use of machine learning techniques for projecting COVID-19 infections and deaths in Mexico. The research has three main objectives: first, to identify which function adjusts the best to the infected population growth in Mexico; second, to determine the feature importance of climate and mobility; third, to compare the results of a traditional time series statistical model with a modern approach in machine learning. The motivation for this work is to support health care providers in their preparation and planning. The methods compared are linear, polynomial, and generalized logistic regression models to describe the growth of COVID-19 incidents in Mexico. Additionally, machine learning and time series techniques are used to identify feature importance and perform forecasting for daily cases and fatalities. The study uses the publicly available data sets from the John Hopkins University of Medicine in conjunction with the mobility rates obtained from Google's Mobility Reports and climate variables acquired from the Weather Online API. The results suggest that the logistic growth model fits best the pandemic's behavior, that there is enough correlation of climate and mobility variables with the disease numbers, and that the Long short-term memory network can be exploited for predicting daily cases. Given this, we propose a model to predict daily cases and fatalities for SARS-CoV-2 using time series data, mobility, and weather variables.

14.
Implement Sci ; 16(1): 50, 2021 May 07.
Article in English | MEDLINE | ID: mdl-33962635

ABSTRACT

BACKGROUND: COVID-19 has presented challenges to healthcare systems and healthcare professionals internationally. After one year of the pandemic, the initial evidence on health system responses begins to consolidate, and there is a need to identify and synthesise experiences of responding to COVID-19 among healthcare professionals and other health system stakeholders. This systematic review of primary qualitative studies depicts the experiences and perceptions of organisations and actors at multiple levels of health systems internationally in responding to COVID-19. METHODS: Six main databases of biomedical information, public health and health administration research were searched over the period October 1, 2019, to October 21, 2020. Information extracted from included studies was analysed thematically. RESULTS: Thirty-four studies were eligible for data extraction. Nine of those studies, of lower methodological quality, were removed from the thematic analysis of study results. Considering the professional level experiences, predominant themes of the studies consisted of the new roles and responsibilities of healthcare workers, burnout and distress, recognition of ´unseen´ healthcare workers, and positive changes and emergent solutions amid the crisis. Organisational level findings of the studies included provision of psychological support, COVID-19 as "catalyst" for change, and exercise of more "open" leadership by managers and health authorities. Continuous training, regulation of working conditions, providing supportive resources, coordinating a diversity of actors, and reviewing and updating regulations were roles identified  at the local health system level. CONCLUSIONS: The experiences of frontline healthcare workers have been the focus of attention of the majority of primary qualitative studies as of October 2020. However, organisational and wider system level studies indicate that some responses to COVID-19 have been characterised by increased emphasis on coordination activities by local health system actors, making service adaptations at pace, and reliance on expanded roles of front-line workers. The need for theory-informed qualitative studies was identified at the organisational level. TRIAL REGISTRATION: CRD42020202875.


Subject(s)
COVID-19 , Communicable Disease Control , Health Facility Administrators/psychology , Health Knowledge, Attitudes, Practice , Health Personnel/psychology , Internationality , Attitude of Health Personnel , Humans , Leadership , SARS-CoV-2
15.
Cell ; 184(10): 2715-2732.e23, 2021 05 13.
Article in English | MEDLINE | ID: mdl-33852912

ABSTRACT

Traumatic brain injury (TBI) is the largest non-genetic, non-aging related risk factor for Alzheimer's disease (AD). We report here that TBI induces tau acetylation (ac-tau) at sites acetylated also in human AD brain. This is mediated by S-nitrosylated-GAPDH, which simultaneously inactivates Sirtuin1 deacetylase and activates p300/CBP acetyltransferase, increasing neuronal ac-tau. Subsequent tau mislocalization causes neurodegeneration and neurobehavioral impairment, and ac-tau accumulates in the blood. Blocking GAPDH S-nitrosylation, inhibiting p300/CBP, or stimulating Sirtuin1 all protect mice from neurodegeneration, neurobehavioral impairment, and blood and brain accumulation of ac-tau after TBI. Ac-tau is thus a therapeutic target and potential blood biomarker of TBI that may represent pathologic convergence between TBI and AD. Increased ac-tau in human AD brain is further augmented in AD patients with history of TBI, and patients receiving the p300/CBP inhibitors salsalate or diflunisal exhibit decreased incidence of AD and clinically diagnosed TBI.


Subject(s)
Alzheimer Disease/etiology , Alzheimer Disease/prevention & control , Brain Injuries, Traumatic/complications , Neuroprotection , tau Proteins/metabolism , Acetylation , Alzheimer Disease/metabolism , Animals , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Biomarkers/blood , Biomarkers/metabolism , Brain Injuries, Traumatic/metabolism , Cell Line , Diflunisal/therapeutic use , Female , Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) , Humans , Male , Mice , Mice, Inbred C57BL , Neurons/metabolism , Salicylates/therapeutic use , Sirtuin 1/metabolism , p300-CBP Transcription Factors/antagonists & inhibitors , p300-CBP Transcription Factors/metabolism , tau Proteins/blood
16.
Scientometrics ; 126(3): 2269-2310, 2021.
Article in English | MEDLINE | ID: mdl-33424051

ABSTRACT

Research universities have a strong devotion and advocacy for research in their core academic mission. This is why they are widely recognized for their excellence in research which make them take the most renowned positions in the different worldwide university leagues. In order to examine the uniqueness of this group of universities we analyze the scientific production of a sample of them in a 5 year period of time. On the one hand, we analyze their preferences in research measured with the relative percentage of publications in the different subject areas, and on the other hand, we calculate the similarity between them in research preferences. In order to select a set of research universities, we studied the leading university rankings of Shanghai, QS, Leiden, and Times Higher Education (THE). Although the four rankings own well established and developed methodologies and hold great prestige, we choose to use THE because data were readily available for doing the study we had in mind. Having done that, we selected the twenty academic institutions ranked with the highest score in the last edition of THE World University Rankings 2020 and to contrast their impact, we also, we compared them with the twenty institutions with the lowest score in this ranking. At the same time, we extracted publication data from Scopus database for each university and we applied bibliometrics indicators from Elsevier's SciVal. We applied the statistical techniques cosine similarity and agglomerative hierarchical clustering analysis to examine and compare affinities in research preferences among them. Moreover, a cluster analysis through VOSviewer was done to classify the total scientific production in the four major fields (health sciences, physical sciences, life sciences and social sciences). As expected, the results showed that top universities have strong research profiles, becoming the leaders in the world in those areas and cosine similarity pointed out that some are more affine among them than others. The results provide clues for enhancing existing collaboration, defining and re-directing lines of research, and seeking for new partnerships to face the current pandemic to find was to tackle down the covid-19 outbreak.

17.
J Med Chem ; 64(2): 1139-1169, 2021 01 28.
Article in English | MEDLINE | ID: mdl-33444025

ABSTRACT

The essential eukaryotic chaperone Hsp90 regulates the form and function of diverse client proteins, many of which govern thermotolerance, virulence, and drug resistance in fungal species. However, use of Hsp90 inhibitors as antifungal therapeutics has been precluded by human host toxicities and suppression of immune responses. We recently described resorcylate aminopyrazoles (RAPs) as the first class of Hsp90 inhibitors capable of discriminating between fungal (Cryptococcus neoformans, Candida albicans) and human isoforms of Hsp90 in biochemical assays. Here, we report an iterative structure-property optimization toward RAPs capable of inhibiting C. neoformans growth in culture. In addition, we report the first X-ray crystal structures of C. neoformans Hsp90 nucleotide binding domain (NBD), as the apoprotein and in complexes with the non-species-selective Hsp90 inhibitor NVP-AUY922 and three RAPs revealing unique ligand-induced conformational rearrangements, which reaffirm the hypothesis that intrinsic differences in protein flexibility can confer selective inhibition of fungal versus human Hsp90 isoforms.


Subject(s)
Antifungal Agents/pharmacology , Cryptococcus neoformans/drug effects , Fungi/drug effects , HSP90 Heat-Shock Proteins/antagonists & inhibitors , Pyrazoles/pharmacology , Animals , Antifungal Agents/chemistry , Cell Line , Cell Survival/drug effects , Crystallography, X-Ray , Humans , Mice , Microbial Sensitivity Tests , Microsomes, Liver/metabolism , Protein Binding , Pyrazoles/chemistry , Species Specificity , Structure-Activity Relationship
18.
Micromachines (Basel) ; 13(1)2021 Dec 31.
Article in English | MEDLINE | ID: mdl-35056237

ABSTRACT

In recent years, additive manufacturing has gained importance in a wide range of research applications such as medicine, biotechnology, engineering, etc. It has become one of the most innovative and high-performance manufacturing technologies of the moment. This review aims to show and discuss the characteristics of different existing additive manufacturing technologies for the construction of micromixers, which are devices used to mix two or more fluids at microscale. The present manuscript discusses all the choices to be made throughout the printing life cycle of a micromixer in order to achieve a high-quality microdevice. Resolution, precision, materials, and price, amongst other relevant characteristics, are discussed and reviewed in detail for each printing technology. Key information, suggestions, and future prospects are provided for manufacturing of micromixing machines based on the results from this review.

19.
J Med Chem ; 63(17): 9773-9786, 2020 09 10.
Article in English | MEDLINE | ID: mdl-32787093

ABSTRACT

A series of N-acyl benzothiazoles shows selective and potent cytotoxicity against cancer cell lines expressing cytochrome P450 4F11. A prodrug form is metabolized by cancer cells into an active inhibitor of stearoyl-CoA desaturase (SCD). Substantial variation on the acyl portion of the inhibitors allowed the identification of (R)-27, which balanced potency, solubility, and lipophilicity to allow proof-of-concept studies in mice. The prodrugs were activated inside the tumor, where they can arrest tumor growth. Together, these observations offer promise that a tumor-activated prodrug strategy might exploit the essentiality of SCD for tumor growth, while avoiding toxicity associated with systemic SCD inhibition.


Subject(s)
Benzothiazoles/pharmacology , Enzyme Inhibitors/pharmacology , Stearoyl-CoA Desaturase/antagonists & inhibitors , Animals , Benzothiazoles/pharmacokinetics , Cell Line, Tumor , Cytochrome P450 Family 4/metabolism , Female , Humans , Mice , Prodrugs/metabolism , Tissue Distribution
20.
Crit Care ; 24(1): 490, 2020 08 07.
Article in English | MEDLINE | ID: mdl-32768001

ABSTRACT

BACKGROUND: With recent advances in technology, patients with acute respiratory distress syndrome (ARDS) and severe acute exacerbations of chronic obstructive pulmonary disease (ae-COPD) could benefit from extracorporeal CO2 removal (ECCO2R). However, current evidence in these indications is limited. A European ECCO2R Expert Round Table Meeting was convened to further explore the potential for this treatment approach. METHODS: A modified Delphi-based method was used to collate European experts' views to better understand how ECCO2R therapy is applied, identify how patients are selected and how treatment decisions are made, as well as to identify any points of consensus. RESULTS: Fourteen participants were selected based on known clinical expertise in critical care and in providing respiratory support with ECCO2R or extracorporeal membrane oxygenation. ARDS was considered the primary indication for ECCO2R therapy (n = 7), while 3 participants considered ae-COPD the primary indication. The group agreed that the primary treatment goal of ECCO2R therapy in patients with ARDS was to apply ultra-protective lung ventilation via managing CO2 levels. Driving pressure (≥ 14 cmH2O) followed by plateau pressure (Pplat; ≥ 25 cmH2O) was considered the most important criteria for ECCO2R initiation. Key treatment targets for patients with ARDS undergoing ECCO2R included pH (> 7.30), respiratory rate (< 25 or < 20 breaths/min), driving pressure (< 14 cmH2O) and Pplat (< 25 cmH2O). In ae-COPD, there was consensus that, in patients at risk of non-invasive ventilation (NIV) failure, no decrease in PaCO2 and no decrease in respiratory rate were key criteria for initiating ECCO2R therapy. Key treatment targets in ae-COPD were patient comfort, pH (> 7.30-7.35), respiratory rate (< 20-25 breaths/min), decrease of PaCO2 (by 10-20%), weaning from NIV, decrease in HCO3- and maintaining haemodynamic stability. Consensus was reached on weaning protocols for both indications. Anticoagulation with intravenous unfractionated heparin was the strategy preferred by the group. CONCLUSIONS: Insights from this group of experienced physicians suggest that ECCO2R therapy may be an effective supportive treatment for adults with ARDS or ae-COPD. Further evidence from randomised clinical trials and/or high-quality prospective studies is needed to better guide decision making.


Subject(s)
Carbon Dioxide/blood , Extracorporeal Circulation/methods , Intensive Care Units , Pulmonary Disease, Chronic Obstructive/therapy , Respiratory Distress Syndrome/therapy , Consensus , Delphi Technique , Europe , Humans
SELECTION OF CITATIONS
SEARCH DETAIL