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1.
Animals (Basel) ; 14(10)2024 May 07.
Article in English | MEDLINE | ID: mdl-38791616

ABSTRACT

Ethical considerations regarding our treatment of animals have gained strength, leading to legislation and a societal focus across various disciplines. This is a subject of study within curricula related to agri-food sciences. The aim was to determine the perceptions of agronomy university students concerning animal welfare in livestock production systems. A survey was conducted to encompass various aspects, from participants' sociodemographic attributes to their attitudes and behaviors regarding animal welfare and the consumption of animal products. Statistical analysis, performed using R software, delved into the associations between participants' characteristics and their perspectives on the ethical, bioethical, and legal dimensions of animal welfare. Associations between demographic factors and ethical viewpoints among students were identified. Gender differences emerged in animal treatment perceptions, while rural and urban environments impacted perspectives on various animals. Bioethical considerations revealed distinctive disparities based on gender and education in concerns regarding animal welfare, value perceptions, evaluations of animal behaviors, and opinions on animal research. It is crucial to distinguish between animal welfare and the ethical considerations arising from coexisting with sentient beings capable of experiencing suffering. Ethical theories provide a lens through which we perceive our obligations toward animals. The responsibility to ensure animal welfare is firmly rooted in recognizing that animals, like humans, experience pain and physical suffering. Consequently, actions causing unjustified suffering or mistreatment, particularly for entertainment purposes, are considered morally unacceptable.

2.
Nat Commun ; 15(1): 2112, 2024 Mar 08.
Article in English | MEDLINE | ID: mdl-38459071

ABSTRACT

Prion diseases are a group of rapidly progressing neurodegenerative disorders caused by the misfolding of the endogenous prion protein (PrPC) into a pathogenic form (PrPSc). This process, despite being the central event underlying these disorders, remains largely unknown at a molecular level, precluding the prediction of new potential outbreaks or interspecies transmission incidents. In this work, we present a method to generate bona fide recombinant prions de novo, allowing a comprehensive analysis of protein misfolding across a wide range of prion proteins from mammalian species. We study more than 380 different prion proteins from mammals and classify them according to their spontaneous misfolding propensity and their conformational variability. This study aims to address fundamental questions in the prion research field such as defining infectivity determinants, interspecies transmission barriers or the structural influence of specific amino acids and provide invaluable information for future diagnosis and therapy applications.


Subject(s)
Prion Diseases , Prions , Animals , Prions/metabolism , Prion Proteins/genetics , Prion Diseases/genetics , Prion Diseases/metabolism , Mammals/metabolism , Protein Folding
3.
Int J Mol Sci ; 25(4)2024 Feb 19.
Article in English | MEDLINE | ID: mdl-38397119

ABSTRACT

A novel and cost-effective heterogeneous catalyst for glycerol carbonate production through transesterification was developed by impregnating smectite clay with K2CO3. Comprehensive structural and chemical analyses, including X-ray diffraction Analysis (XRD), Scanning Electron Microscopy (SEM)-Electron Dispersion Spectroscopy (EDS), Fourier Transform Infrared Spectroscopy (FTIR), and Brunauer-Emmett-Teller (BET) surface area analysis measurements, were employed to characterize the catalysts. Among the various catalysts prepared, the one impregnated with 40 wt% K2CO3 on smectite and calcined at 550 °C exhibited the highest catalytic activity, primarily due to its superior basicity. To enhance the efficiency of the transesterification process, several reaction parameters were optimized, including the molar ratio between propylene carbonate and glycerol reactor loading of the catalyst and reaction temperature. The highest glycerol carbonate conversion rate, approximately 77.13% ± 1.2%, was achieved using the best catalyst under the following optimal conditions: 2 wt% reactor loading, 110 °C reaction temperature, 2:1 propylene carbonate to glycerol molar ratio, and 6h reaction duration. Furthermore, both the raw clay and the best calcined K2CO3-impregnated catalysts demonstrated remarkable stability, maintaining their high activity for up to four consecutive reaction cycles. Finally, a kinetic analysis was performed using kinetic data from several runs employing raw clay and the most active K2CO3-modified clay at different temperatures, observing that a simple reversible second-order potential kinetic model of the quasi-homogeneous type fits perfectly to such data in diverse temperature ranges.


Subject(s)
Carbonates , Glycerol , Propane/analogs & derivatives , Silicates , Clay , Kinetics
4.
J Community Health ; 49(2): 324-329, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37940735

ABSTRACT

In the U.S., communities often rely on the criminal justice system to respond to, house, and treat individuals with mental health and substance use problems. This has resulted in a crisis response system that relies on police officers to respond to mental and behavioral health crisis due to a lack of options. Unfortunately, these encounters can be dangerous for individuals in need of help. Additionally, this has led to a disproportionate number of individuals with mental illness and substance use disorders being housed in prisons. Alternatives to our current crisis response system already exist in the form of community-based mobile crisis response teams that rely on mental health workers instead of law enforcement. This review examines such programs that have been enacted in multiple cities across the country. Analysis of these alternative crisis response models shows that community-based programs are more effective, efficient, and safer than the current standard that relies on law enforcement. This analysis highlights the need for the establishment of community-based crisis response teams as the national standard.


Subject(s)
Mental Disorders , Substance-Related Disorders , Humans , Crisis Intervention , Mental Disorders/therapy , Mental Disorders/psychology , Law Enforcement , Police , Substance-Related Disorders/therapy , Substance-Related Disorders/psychology , Mental Health
5.
Sci Adv ; 9(45): eadi5520, 2023 Nov 10.
Article in English | MEDLINE | ID: mdl-37939188

ABSTRACT

Arranging semiconducting nanocrystals into ordered superstructures is a promising platform to study fundamental light-matter interactions and develop programmable optical metamaterials. We investigated how the geometrical arrangement of CdS nanocrystals in hierarchical assemblies affects chiroptical properties. To create these structures, we controlled the evaporation of a colloidal CdS nanocrystal solution between two parallel plates. We combined in situ microscopy and computational modeling to establish a formation mechanism involving the shear-induced alignment of nanocrystal fibers and the subsequent mechanical relaxation of the stretched fibers to form Raman noodle-type band textures. The high linear anisotropy in these films shares many similarities with cholesteric liquid crystals. The films deposited on top and bottom surfaces exhibit opposite chirality. The mechanistic insights from this study are consequential to enable future advances in the design and fabrication of programmable optical metamaterials for further development of polarization-based optics toward applications in sensing, hyperspectral imaging, and quantum information technology.

6.
Environ Geochem Health ; 45(12): 9891-9901, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37882916

ABSTRACT

Exposure to heavy metals may cause the overproduction of reactive oxygen species, generating oxidative stress and consequently, various harms to human health. The soil surrounding the Ventanas Industrial Complex, in Puchuncaví and Quintero municipal districts on the central Chilean coast, contains heavy metal concentrations (As, Cu, Pb, Zn, among others) that far exceed the maximum permissible levels established by Italian soil standards (used as a reference). This study aimed to investigate the potential association between heavy metal exposure in humans and the levels of oxidative stress biomarkers in inhabitants of these locations. We took blood samples from 140 adults living in sites with high concentrations of heavy metals in the soil and compared them with blood samples from 140 adults living in areas with normal heavy metal concentrations. We assessed lipid peroxidation, damage to genetic material, and Total Antioxidant Capacity in these blood samples. Our results indicate an association between oxidative damage and heavy metal exposure, where the inhabitants living in exposed areas have a higher level of DNA damage compared with those living in control areas. Given that DNA damage is one of the main factors in carcinogenesis, these results are of interest, both for public health and for public policies aimed at limiting human exposure to environmental pollution.


Subject(s)
Metals, Heavy , Soil Pollutants , Adult , Humans , Chile , Environmental Monitoring/methods , Metals, Heavy/toxicity , Metals, Heavy/analysis , Oxidative Stress , Soil , Soil Pollutants/toxicity , Soil Pollutants/analysis , Risk Assessment , China
7.
Acta Neuropathol Commun ; 11(1): 145, 2023 09 07.
Article in English | MEDLINE | ID: mdl-37679832

ABSTRACT

Among transmissible spongiform encephalopathies or prion diseases affecting humans, sporadic forms such as sporadic Creutzfeldt-Jakob disease are the vast majority. Unlike genetic or acquired forms of the disease, these idiopathic forms occur seemingly due to a random event of spontaneous misfolding of the cellular PrP (PrPC) into the pathogenic isoform (PrPSc). Currently, the molecular mechanisms that trigger and drive this event, which occurs in approximately one individual per million each year, remain completely unknown. Modelling this phenomenon in experimental settings is highly challenging due to its sporadic and rare occurrence. Previous attempts to model spontaneous prion misfolding in vitro have not been fully successful, as the spontaneous formation of prions is infrequent and stochastic, hindering the systematic study of the phenomenon. In this study, we present the first method that consistently induces spontaneous misfolding of recombinant PrP into bona fide prions within hours, providing unprecedented possibilities to investigate the mechanisms underlying sporadic prionopathies. By fine-tuning the Protein Misfolding Shaking Amplification method, which was initially developed to propagate recombinant prions, we have created a methodology that consistently produces spontaneously misfolded recombinant prions in 100% of the cases. Furthermore, this method gives rise to distinct strains and reveals the critical influence of charged surfaces in this process.


Subject(s)
Creutzfeldt-Jakob Syndrome , Prions , Humans , Magnetic Resonance Imaging , Tremor
8.
Rev. Costarric. psicol ; 42(1): 65-80, ene.-jun. 2023. tab
Article in Spanish | LILACS, SaludCR | ID: biblio-1559028

ABSTRACT

Resumen Durante la pandemia por COVID-19 se dio una acelerada virtualización de los procesos de atención psicológica en Costa Rica, en paralelo a la expansión en la regulación de esta modalidad por parte del Colegio de Profesionales en Psicología de Costa Rica. El presente artículo tiene el objetivo de identificar valoraciones de personas del gremio de profesionales en psicología de Costa Rica sobre sus habilidades terapéuticas y técnicas para ejercer psicoterapia clínica individual mediante las Tecnologías de la Información y Comunicación (TIC) durante la Pandemia por COVID-19. Mediante la aplicación de un cuestionario autoadministrado en línea, se realizó un acercamiento al gremio, donde se consultó sobre las estrategias, herramientas y habilidades que puso en práctica para comenzar a utilizar las TIC en su ejercicio psicoterapéutico. Se obtuvieron experiencias muy importantes, aprendizajes sobre la marcha y, sobre todo, la ausencia de un consenso y claridad entre las personas profesionales en psicología sobre las buenas prácticas para el uso de esta modalidad. Como principal reflexión del proceso, se invita al gremio a ejercitar al máximo las habilidades de terapeuta, especialmente aquellas que quizá no resulten empleadas regularmente durante una consulta a distancia, como la observación y el examen clínico integral.


Abstract During the COVID-19 Pandemic, the virtualization of psychological care grew rapidly in Costa Rica, parallel to the expansion of regulation for this modality in the Colegio de Profesionales en Psicología de Costa Rica. The objective of this article is to identify the appraisals of Costa Rican psychology professionals regarding their abilities to practice individual clinical psychotherapy by means of Information and Communication Technologies (ICT) during the COVID-19 Pandemic. Through the completion of a self-administered online questionnaire, professionals were consulted about the strategies, tools and skills that they put into play during the use of ICTs in their psychotherapeutic practice, narrating deeply important experiences, presenting key learnings and above all, making visible the absence of a consensus and clarity regarding the best practices for use in this modality. The main recommendation emanating from this process is to promote to the maximum continuing-education on the topic of therapist skills, especially those that may not be used regularly during a remote consultation, such as observation and comprehensive clinical examination.


Subject(s)
Humans , Male , Female , Psychology , Psychotherapeutic Processes , Education, Distance , Videoconferencing/trends , Costa Rica , Virtual Reality , COVID-19
9.
Molecules ; 28(3)2023 Jan 30.
Article in English | MEDLINE | ID: mdl-36770980

ABSTRACT

With the advent of biodiesel as a substitute/additive for diesel, the production of glycerol has experienced an increase, as it is an unavoidable byproduct of the biodiesel process; therefore, novel products and processes based on this triol are being very actively researched. Glycerol carbonate emerges as an advanced humectant from glycerol and a monomer for diverse polycarbonates. Its production in high yields and amounts can be achieved through the solventless transcarbonation of glycerol with other organic carbonates driven by alkaline catalysts, standing out amongst the cyclic carbonates due to its reactivity. Here, we have studied the main operational variables that affect the transcarbonation reaction of glycerol and ethylene carbonate catalyzed by zinc stearate: catalyst concentration, reagent molar ratio, and temperature. Subsequently, an appropriate kinetic model was fitted to all data obtained at 80 °C and several catalyst concentrations as well as reagent molar ratios. Finally, the selected kinetic model was extended and validated by fitting it to data obtained at several temperatures, finding that the activation energy of this reaction with this catalyst is around 69.2 kJ·mol-1. The kinetic model suggests that the reaction is bimolecular and elemental and that the process is interfacial in essence, with the catalyst dispersed in a narrow space between polar (glycerol) and nonpolar (ethylene carbonate) phases.

10.
mBio ; 14(1): e0313622, 2023 02 28.
Article in English | MEDLINE | ID: mdl-36625656

ABSTRACT

Coronaviruses (CoVs) of genera α, ß, γ, and δ encode proteins that have a PDZ-binding motif (PBM) consisting of the last four residues of the envelope (E) protein (PBM core). PBMs may bind over 400 cellular proteins containing PDZ domains (an acronym formed by the combination of the first letter of the names of the three first proteins where this domain was identified), making them relevant for the control of cell function. Three highly pathogenic human CoVs have been identified to date: severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2. The PBMs of the three CoVs were virulence factors. SARS-CoV mutants in which the E protein PBM core was replaced by the E protein PBM core from virulent or attenuated CoVs were constructed. These mutants showed a gradient of virulence, depending on whether the alternative PBM core introduced was derived from a virulent or an attenuated CoV. Gene expression patterns in the lungs of mice infected with SARS-CoVs encoding each of the different PBMs were analyzed by RNA sequencing of infected lung tissues. E protein PBM of SARS-CoV and SARS-CoV-2 dysregulated gene expression related to ion transport and cell homeostasis. Decreased expression of cystic fibrosis transmembrane conductance regulator (CFTR) mRNA, essential for alveolar edema resolution, was shown. Reduced CFTR mRNA levels were associated with edema accumulation in the alveoli of mice infected with SARS-CoV and SARS-CoV-2. Compounds that increased CFTR expression and activity, significantly reduced SARS-CoV-2 growth in cultured cells and protected against mouse infection, suggesting that E protein virulence is mediated by a decreased CFTR expression. IMPORTANCE Three highly pathogenic human CoVs have been identified: SARS-CoV, MERS-CoV, and SARS-CoV-2. The E protein PBMs of these three CoVs were virulence factors. Gene expression patterns associated with the different PBM motifs in the lungs of infected mice were analyzed by deep sequencing. E protein PBM motif of SARS-CoV and SARS-CoV-2 dysregulated the expression of genes related to ion transport and cell homeostasis. A decrease in the mRNA expression of the cystic fibrosis transmembrane conductance regulator (CFTR), which is essential for edema resolution, was observed. The reduction of CFTR mRNA levels was associated with edema accumulation in the lungs of mice infected with SARS-CoV-2. Compounds that increased the expression and activity of CFTR drastically reduced the production of SARS-CoV-2 and protected against its infection in a mice model. These results allowed the identification of cellular targets for the selection of antivirals.


Subject(s)
COVID-19 , Middle East Respiratory Syndrome Coronavirus , Severe acute respiratory syndrome-related coronavirus , Animals , Mice , Humans , SARS-CoV-2/genetics , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Severe acute respiratory syndrome-related coronavirus/genetics , Virulence Factors/genetics , Virulence Factors/metabolism , Middle East Respiratory Syndrome Coronavirus/genetics , Lung/metabolism , RNA, Messenger
11.
Molecules ; 27(21)2022 Oct 28.
Article in English | MEDLINE | ID: mdl-36364146

ABSTRACT

Schinus molle is a plant traditionally used in Mexico to treat gastric disorders. However, no scientific evidence has been reported on its gastroprotective effect. The aim of the current contribution was to conduct a bioassay-guided study on S. molle to evaluate its gastroprotective activity in a model of Wistar rats given ethanol orally to induce gastric lesions. The hexane and dichloromethane extracts from the tested plant showed over 99% gastroprotection at a dose of 100 mg/kg. From the hexane extract, two of the three fractions (F1 and F2) afforded over 99% gastroprotection. The F1 fraction was subjected to column chromatography, which revealed a white solid. Based on the ESI-MS analysis, the two main compounds in this solid were identified. The predominant compound was probably a triterpene. This mixture of compounds furnished about 67% gastroprotection at a dose of 100 mg/kg. Pretreatment with L-NAME, indomethacin, and NEM was carried out to explore the possible involvement of nitric oxide, prostaglandins, and/or sulfhydryl groups, respectively, in the gastroprotective activity of the white solid. We found evidence for the participation of all three factors. No antisecretory activity was detected (tested by pylorus ligation). In conclusion, evidence is herein provided for the first time of the gastroprotective effect of S. molle.


Subject(s)
Anacardiaceae , Anti-Ulcer Agents , Stomach Ulcer , Rats , Animals , Prostaglandins/pharmacology , Nitric Oxide/pharmacology , Stomach Ulcer/chemically induced , Stomach Ulcer/drug therapy , Stomach Ulcer/pathology , Anti-Ulcer Agents/chemistry , Hexanes/pharmacology , Rats, Wistar , Sulfhydryl Compounds/pharmacology , Plant Extracts/chemistry , Gastric Mucosa
12.
Curr Res Immunol ; 3: 151-158, 2022.
Article in English | MEDLINE | ID: mdl-35966177

ABSTRACT

Coronaviruses (CoVs) have the largest genome among RNA viruses and store large amounts of information without genome integration as they replicate in the cell cytoplasm. The replication of the virus is a continuous process, whereas the transcription of the subgenomic mRNAs is a discontinuous one, involving a template switch, which resembles a high frequency recombination mechanism that may favor virus genome variability. The origin of the three deadly human CoVs SARS-CoV, MERS-CoV and SARS-CoV-2 are zoonotic events. SARS-CoV-2 has incorporated in its spike protein a furine proteolytic site that facilitates the activation of the virus in any tissue, making this CoV strain highly polytropic and pathogenic. Using MERS-CoV as a model, a propagation-deficient RNA replicon was generated by removing E protein gene (essential for viral morphogenesis and involved in virulence), and accessory genes 3, 4a, 4b and 5 (responsible for antagonism of the innate immune response) to attenuate the virus: MERS-CoV-Δ[3,4a,4b,5,E]. This RNA replicon is strongly attenuated and elicits sterilizing protection after a single immunization in transgenic mice with the receptor for MERS-CoV, making it a promising vaccine candidate for this virus and an interesting platform for vector-based vaccine development. A strategy could be developed for the design of RNA replicon vaccines for other human pathogenic coronaviruses.

13.
Environ Sci Pollut Res Int ; 29(32): 48250-48259, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35188613

ABSTRACT

Gene expression can be modified in people who are chronically exposed to high concentrations of heavy metals. The soil surrounding the Ventanas Industrial Complex, located on the coastal zone of Puchuncaví and Quintero townships (Chile), contain heavy metal concentrations (As, Cu, Pb, Zn, among others) that far exceed international standards. The aim of this study was to determine the potential association of the heavy metals in soils, especially arsenic, with the status of methylation of four tumor suppressor genes in permanent residents in those townships. To study the methylation status in genes p53, p16, APC, and RASSF1A, we took blood samples from adults living in areas near the industrial complex for at least 5 years and compared it to blood samples from adults living in areas with normal heavy metal concentrations of soils. Results indicated that inhabitants of an area with high levels of heavy metals in soil have a significantly higher proportion of methylation in the promoter region of the p53 tumor suppressor gene compared with control areas (p-value: 0.0035). This is the first study to consider associations between heavy metal exposure in humans and aberrant DNA methylation in Chile. Our results suggest more research to support consistent decision-making on processes of environmental remediation or prevention of exposure.


Subject(s)
Arsenic , Metals, Heavy , Soil Pollutants , Adult , Arsenic/analysis , Blood Cells/chemistry , Chile , China , Cross-Sectional Studies , Environmental Monitoring/methods , Genes, p53 , Humans , Metals, Heavy/analysis , Methylation , Soil , Soil Pollutants/analysis , Tumor Suppressor Protein p53/genetics
14.
J Plast Reconstr Aesthet Surg ; 75(3): 1048-1056, 2022 03.
Article in English | MEDLINE | ID: mdl-34848129

ABSTRACT

Hand burns are common injuries that can result in long-term impairment of hand function. Enzymatic debridement (ED) prevents damage to the viable dermis due to the procedure's selectivity and has become an option for obtaining an accurate depth assessment and enabling wound re-epithelialization with less skin graft use. We conducted a prospective study from July 2015 to July 2018, which enrolled patients with deep partial-thickness hand burns and treated them with ED using bromelain. After a specified period, we assessed the patients' hand function, using the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire and the Michigan Hand Outcomes Questionnaire (MHOQ) to assess their disabilities and activities of daily life, respectively. We assessed the hand joint range of motion using a goniometer and assessed scar quality with the Vancouver Scar Scale (VSS). We analyzed 72 patients with 90 burned hands at 3 months and, at the final assessment, 69 patients with 86 burned hands. Fire was the most common cause of the burns. Bromelain allowed for early debridement (73.6% during the first 24 h). At the 3-month evaluation, the mean DASH and MHOQ scores were 2.35 and 97.9%, respectively, with a high inverse correlation between the 2 types of scores (Spearman's rho, -0.78; p < .001). The mean wrist flexion and extension were 85.7 and 80°, respectively, the mean metacarpophalangeal flexion was 88.3°, the proximal interphalangeal (PIP) flexion was 112.9°, and the thumb opposition was 77°. The mean VSS score was 2.87. At the final evaluation, with a minimum follow-up of 391 days, the mean DASH and MHOQ scores were 0.18 and 99.71%, respectively. ED with bromelain in deep partial-thickness hand burns resulted in normal values at 3 months and at over 1 year of follow-up, with complete restoration of function and quality of life and good scar results.


Subject(s)
Burns , Hand Injuries , Burns/surgery , Debridement/methods , Hand Injuries/surgery , Humans , Prospective Studies , Quality of Life , Skin Transplantation
15.
Proc Natl Acad Sci U S A ; 118(43)2021 10 26.
Article in English | MEDLINE | ID: mdl-34686605

ABSTRACT

Self-amplifying RNA replicons are promising platforms for vaccine generation. Their defects in one or more essential functions for viral replication, particle assembly, or dissemination make them highly safe as vaccines. We previously showed that the deletion of the envelope (E) gene from the Middle East respiratory syndrome coronavirus (MERS-CoV) produces a replication-competent propagation-defective RNA replicon (MERS-CoV-ΔE). Evaluation of this replicon in mice expressing human dipeptidyl peptidase 4, the virus receptor, showed that the single deletion of the E gene generated an attenuated mutant. The combined deletion of the E gene with accessory open reading frames (ORFs) 3, 4a, 4b, and 5 resulted in a highly attenuated propagation-defective RNA replicon (MERS-CoV-Δ[3,4a,4b,5,E]). This RNA replicon induced sterilizing immunity in mice after challenge with a lethal dose of a virulent MERS-CoV, as no histopathological damage or infectious virus was detected in the lungs of challenged mice. The four mutants lacking the E gene were genetically stable, did not recombine with the E gene provided in trans during their passage in cell culture, and showed a propagation-defective phenotype in vivo. In addition, immunization with MERS-CoV-Δ[3,4a,4b,5,E] induced significant levels of neutralizing antibodies, indicating that MERS-CoV RNA replicons are highly safe and promising vaccine candidates.


Subject(s)
Coronavirus Infections/prevention & control , Middle East Respiratory Syndrome Coronavirus/genetics , Middle East Respiratory Syndrome Coronavirus/immunology , RNA, Viral/administration & dosage , Replicon , Viral Vaccines/administration & dosage , Animals , Antibodies, Neutralizing/biosynthesis , Antibodies, Viral/biosynthesis , Coronavirus Infections/genetics , Coronavirus Infections/immunology , Coronavirus Infections/virology , Defective Viruses/genetics , Defective Viruses/immunology , Female , Gene Deletion , Genes, env , Humans , Mice , Mice, Inbred C57BL , Mice, Transgenic , Middle East Respiratory Syndrome Coronavirus/pathogenicity , RNA, Viral/genetics , RNA, Viral/immunology , Vaccines, DNA , Vaccines, Virus-Like Particle/administration & dosage , Vaccines, Virus-Like Particle/genetics , Vaccines, Virus-Like Particle/immunology , Viral Vaccines/genetics , Viral Vaccines/immunology , Virulence/genetics , Virulence/immunology
16.
Front Bioeng Biotechnol ; 8: 589182, 2020.
Article in English | MEDLINE | ID: mdl-33195153

ABSTRACT

Transmissible spongiform encephalopathies (TSEs) are a group of invariably fatal neurodegenerative disorders. The causal agent is an aberrantly folded isoform (PrPSc or prion) of the endogenous prion protein (PrPC) which is neurotoxic and amyloidogenic and induces misfolding of its physiological counterpart. The intrinsic physical characteristics of these infectious proteinaceous pathogens makes them highly resistant to the vast majority of physicochemical decontamination procedures used typically for standard disinfection. This means prions are highly persistent in contaminated tissues, the environment (surfaces) and, of great concern, on medical and surgical instruments. Traditionally, decontamination procedures for prions are tested on natural isolates coming from the brain of infected individuals with an associated high heterogeneity resulting in highly variable results. Using our novel ability to produce highly infectious recombinant prions in vitro we adapted the system to enable recovery of infectious prions from contaminated materials. This method is easy to perform and, importantly, results in highly reproducible propagation in vitro. It exploits the adherence of infectious prion protein to beads of different materials allowing accurate and repeatable assessment of the efficacy of disinfectants of differing physicochemical natures to eliminate infectious prions. This method is technically easy, requires only a small shaker and a standard biochemical technique and could be performed in any laboratory.

17.
Cir. plást. ibero-latinoam ; 46(supl.1): S75-S84, abr. 2020. tab, ilus, graf
Article in Spanish | IBECS | ID: ibc-193496

ABSTRACT

INTRODUCCIÓN Y OBJETIVO: El desbridamiento enzimático ha demostrado ser eficaz y rápido en su aplicación sobre quemaduras, a la vez que conservador con el tejido sano. Su uso sobre quemaduras inferiores al 15% ha mostrado reducir la cantidad de injertos, el sangrado y las escarotomías quirúrgicas. El objetivo de este estudio es comparar 2 grupos de pacientes grandes quemados, uno tratado mediante desbridamiento enzimático frente a otro tratado mediante tratamiento estándar, y su impacto en la estancia hospitalaria, necesidades de escarotomías, tiempo hasta desbridamiento, uso de hemoderivados y cantidad de cirugías durante el ingreso. MATERIAL Y MÉTODO: Estudio de cohortes retrospectivas con 197 pacientes (SCQ 20-50%), mayores de 18 años, tratados entre 2012 y 2017, con 2 grupos: 32 pacientes tratados con Nexobrid® para el desbridamiento enzimático, y 165 pacientes en el grupo control con desbridamiento tangencial convencional. Ambos homogéneos para SCQ, edad, sexo, mecanismo de lesión y comorbilidades. RESULTADOS: La edad media fue de 48.4 ± 19.4 años, con una SCQ media de 29.5 ± 9.4%. Observamos disminución del tiempo hasta el inicio del desbridamiento de la quemadura (5.1 ± 4.9 días en el grupo control frente a 0.8±0.9 en el grupo de desbridamiento enzimático, p < 0.05). El grupo de Nexobrid® presentó una reducción de la cantidad de tiempos quirúrgicos durante su ingreso, siendo de 1.9±2.0 frente a 2.6±2.1 en el grupo control. El uso de hemoderivados se redujo en un 95% durante el desbridamiento. La necesidad de escarotomías se redujo un 60%. Finalmente, el grupo de Nexobrid® tuvo un 36% menos de estancia en la Unidad de Quemados Críticos, con diferencias estadísticamente significativas. CONCLUSIONES: La aplicación precoz del desbridamiento enzimático en grandes quemados (20-50% SCQ), permite la escarectomía completa del paciente reduciendo la necesidad de hemoderivados, el número de tiempos quirúrgicos, las escarotomías y la estancia en la unidad de cuidados intensivos


BACKGROUND AND OBJECTIVE: Use of enzymatic debridement has demonstrated be fast and efficient after its application over burn wounds, being more delicate over healthy tissue. Its use in burns under 15% TBSA has shown less grafting procedures, bleeding and surgical escharotomies. The aim of this study was compare 2 groups of major burns; one treated by enzymatic debridement and other treated by standard of care. Length of stay, escharotomies, time until debridement, use of blood packs and number of surgeries during hospitalization were evaluated. METHODS: A retrospective cohort study was designed with 197 patients (TBSA 20-50%), older than 18 years old, treated between 2012 and 2017, and divided in 2 groups: 32 patients were debrided using Nexobrid®, and 165 patients were included in the control group. Both groups were homogeneous for TBSA, age, gender, mechanism and comorbidities index. RESULTS: Mean age was 48.4±19.4 years, with a 29.5±9.4% of TBSA. A reduction of the number of days until the burns debridement were found, with 5.1±4.9 in the control group and 0.8±0.9 days in the enzymatic debridement group (p < 0.05). The number of surgeries during the hospitalization were less in the Nexobrid® group, with a reduction of 2.6±2.1 surgeries to 1.9±2.0. The number of blood packs was a 95% lower in the enzymatic debridement, and a 60% less escharotomies were observed. Finally, a shorter length of stay in the intensive care unit were found in the Nexobrid® group, with 36% less days, this difference were statistically significant. CONCLUSIONS: Early application of enzymatic debridement in major burns (20-50% TBSA) allows a complete removal of eschar reducing the blood packs use, number of surgeries, escharotomies and length of stay in the intensive care unit


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Burns/surgery , Debridement/methods , Skin Ulcer/therapy , Cohort Studies , Bromelains/therapeutic use , Peptide Hydrolases/therapeutic use , Retrospective Studies , Length of Stay , Cicatrix/surgery
18.
Biomolecules ; 10(3)2020 03 19.
Article in English | MEDLINE | ID: mdl-32204429

ABSTRACT

Transmissible spongiform encephalopathies or prion diseases are rapidly progressive neurodegenerative diseases, the clinical manifestation of which can resemble other promptly evolving neurological maladies. Therefore, the unequivocal ante-mortem diagnosis is highly challenging and was only possible by histopathological and immunohistochemical analysis of the brain at necropsy. Although surrogate biomarkers of neurological damage have become invaluable to complement clinical data and provide more accurate diagnostics at early stages, other neurodegenerative diseases show similar alterations hindering the differential diagnosis. To solve that, the detection of the pathognomonic biomarker of disease, PrPSc, the aberrantly folded isoform of the prion protein, could be used. However, the amounts in easily accessible tissues or body fluids at pre-clinical or early clinical stages are extremely low for the standard detection methods. The solution comes from the recent development of in vitro prion propagation techniques, such as Protein Misfolding Cyclic Amplification (PMCA) and Real Time-Quaking Induced Conversion (RT-QuIC), which have been already applied to detect minute amounts of PrPSc in different matrixes and make early diagnosis of prion diseases feasible in a near future. Herein, the most relevant tissues and body fluids in which PrPSc has been detected in animals and humans are being reviewed, especially those in which cell-free prion propagation systems have been used with diagnostic purposes.


Subject(s)
PrPSc Proteins/metabolism , Prion Diseases/diagnosis , Cell-Free System/chemistry , Cell-Free System/metabolism , Humans , PrPSc Proteins/chemistry , Prion Diseases/metabolism
19.
Environ Pollut ; 258: 113488, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31859123

ABSTRACT

The townships of Puchuncaví and Quintero, on the coast of central Chile, have soils contaminated by atmospheric deposition of sulfur dioxide and trace elements from the nearby Ventanas Industrial Complex. The purpose of this study was to evaluate potential human health and ecological risks, by determining the spatial distribution of soil total concentrations arsenic (As), copper (Cu), lead (Pb), and zinc (Zn) in these townships. Total concentrations of these elements were determined in 245 topsoil samples, used to generate continuous distribution maps. The background concentrations of Cu, As, Pb, and Zn in the studied soils were 100, 16, 35, and 122 mg kg-1, respectively. The concentrations of Cu, As, and Pb were positively correlated with each other, suggesting that their source is the Ventanas copper smelter. On the other hand, correlations for Zn were weaker than for other trace elements, suggesting low impact of the Ventanas copper smelter on spatial distribution of Zn. Indeed, only 6% of the study area exhibited Zn concentrations above the background level. In contrast, 77, 32 and 35% of the study area presented Cu, As, and Pb concentrations, respectively, above the background level. The carcinogenic risk due to exposure to As was above the threshold value of 10-04 in the population of young children (1-5 years old) on 27% of the study area. These risk values are classified as unacceptable, which require specific intervention by the Chilean government. Based on the estimated concentrations of exchangeable Cu, 10, 15, and 75% of the study area exhibited high, medium, and low phytotoxicity risk, respectively.


Subject(s)
Air Pollutants/analysis , Arsenic/analysis , Copper/analysis , Environmental Exposure/analysis , Lead/analysis , Risk Assessment/methods , Soil Pollutants/analysis , Soil/chemistry , Zinc/analysis , Arsenic/toxicity , Child , Child, Preschool , Chile , Copper/toxicity , Environmental Exposure/adverse effects , Environmental Monitoring/methods , Humans , Industry , Infant , Lead/toxicity , Metals, Heavy , Spatial Analysis , Zinc/toxicity
20.
PLoS Pathog ; 15(10): e1008117, 2019 10.
Article in English | MEDLINE | ID: mdl-31644574

ABSTRACT

The resolution of the three-dimensional structure of infectious prions at the atomic level is pivotal to understand the pathobiology of Transmissible Spongiform Encephalopathies (TSE), but has been long hindered due to certain particularities of these proteinaceous pathogens. Difficulties related to their purification from brain homogenates of disease-affected animals were resolved almost a decade ago by the development of in vitro recombinant prion propagation systems giving rise to highly infectious recombinant prions. However, lack of knowledge about the molecular mechanisms of the misfolding event and the complexity of systems such as the Protein Misfolding Cyclic Amplification (PMCA), have limited generating the large amounts of homogeneous recombinant prion preparations required for high-resolution techniques such as solid state Nuclear Magnetic Resonance (ssNMR) imaging. Herein, we present a novel recombinant prion propagation system based on PMCA that substitutes sonication with shaking thereby allowing the production of unprecedented amounts of multi-labeled, infectious recombinant prions. The use of specific cofactors, such as dextran sulfate, limit the structural heterogeneity of the in vitro propagated prions and makes possible, for the first time, the generation of infectious and likely homogeneous samples in sufficient quantities for studies with high-resolution structural techniques as demonstrated by the preliminary ssNMR spectrum presented here. Overall, we consider that this new method named Protein Misfolding Shaking Amplification (PMSA), opens new avenues to finally elucidate the three-dimensional structure of infectious prions.


Subject(s)
Nuclear Magnetic Resonance, Biomolecular/methods , Prion Proteins/metabolism , Prions/metabolism , Animals , Arvicolinae , Central Nervous System/pathology , Dextran Sulfate/pharmacology , Disease Models, Animal , Mice, Transgenic , Prion Diseases/pathology , Protein Structure, Tertiary , Proteostasis Deficiencies/pathology
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