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1.
ACS Appl Polym Mater ; 6(15): 9088-9098, 2024 Aug 09.
Article in English | MEDLINE | ID: mdl-39144280

ABSTRACT

Mixed matrix membranes (MMMs) were formed by using seven polymeric matrices with a wide range of permeabilities. All of the polymeric matrices have been polyimides, namely: P84, Pi-DAPOH, Pi-DAROH, Matrimid, Pi-HABAc, PI-DAM, and PIM-1 in the order of increasing O2 permeability. A fixed (10%) concentration of a microporous organic polymer (TFAP-Trp), formed by the combination of trifluoroacetophenone and triptycene, was added as a porous filler. The material properties as well as their separation performances for multiple pure gases, specifically the permeabilities of He, N2, O2, CH4, and CO2, were measured. The correlation between the relative increase in permeability in MMMs and that of the matrix polymeric membrane has been quantitatively analyzed. This study proves that the increased permeability of MMMs is largely linked to the contribution of the high permeability of the filler. The addition of the TFAP-Trp porous filler proves to be especially beneficial for matrices with low to moderate permeabilities, significantly enhancing the matrix permeability overall. The fitted relationship is approximately linear in accordance with the existing models to predict permeability in dual-phase systems for low proportions of the dispersed phase. An extrapolation allows the evaluation of the permeability of the pure microporous organic polymer, which agrees with the previous values described by the group for different filler contents and in other polymeric matrices. In all cases, the selectivity remains approximately constant while the permeability increases. The addition of TFAP-Trp to all the polymeric matrices led to a moderate improvement of the MMM separation performances, mainly centered on their permeabilities.

2.
Foods ; 13(13)2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38998637

ABSTRACT

An increasing number of food companies are voluntarily adopting environmental policies and sustainability initiatives to tackle climate change. The aims of this study were to analyse the presence of environmental labels on table olive products, to explore consumer perceptions of these companies' environmental commitment and initiatives, and to evaluate the influence of these messages on purchasing decisions. For this purpose, a market study was conducted in different hypermarkets and supermarkets in Spain, and an online survey was submitted to consumers (n = 227). The results show that environmental claims and/or certifications related to sustainability do not appear on table olive products, despite most of the companies that produce and/or market table olives having adopted environmental and sustainability policies and commitments (34.3% have their environmental policy published on their website). More than 85% of consumers positively value these companies' sustainability commitments and consider environmental initiatives to be very important. As a sector of consumers pays close attention to environmental commitments, it would be interesting for table olive companies to identify their sustainability policies on their products' labelling to, thus, facilitate pro-environmental consumer purchase choices. These results could help the food industry develop the best strategies to publicise their social and environmental policies and commitments.

3.
Dev Cell ; 59(13): 1655-1667.e6, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38670102

ABSTRACT

Proteotoxic stress drives numerous degenerative diseases. Cells initially adapt to misfolded proteins by activating the unfolded protein response (UPR), including endoplasmic-reticulum-associated protein degradation (ERAD). However, persistent stress triggers apoptosis. Enhancing ERAD is a promising therapeutic approach for protein misfolding diseases. The ER-localized Zn2+ transporter ZIP7 is conserved from plants to humans and required for intestinal self-renewal, Notch signaling, cell motility, and survival. However, a unifying mechanism underlying these diverse phenotypes was unknown. In studying Drosophila border cell migration, we discovered that ZIP7-mediated Zn2+ transport enhances the obligatory deubiquitination of proteins by the Rpn11 Zn2+ metalloproteinase in the proteasome lid. In human cells, ZIP7 and Zn2+ are limiting for deubiquitination. In a Drosophila model of neurodegeneration caused by misfolded rhodopsin (Rh1), ZIP7 overexpression degrades misfolded Rh1 and rescues photoreceptor viability and fly vision. Thus, ZIP7-mediated Zn2+ transport is a previously unknown, rate-limiting step for ERAD in vivo with therapeutic potential in protein misfolding diseases.


Subject(s)
Cation Transport Proteins , Drosophila Proteins , Endoplasmic Reticulum-Associated Degradation , Endoplasmic Reticulum , Zinc , Animals , Cation Transport Proteins/metabolism , Cation Transport Proteins/genetics , Zinc/metabolism , Drosophila Proteins/metabolism , Drosophila Proteins/genetics , Humans , Endoplasmic Reticulum/metabolism , Proteasome Endopeptidase Complex/metabolism , Proteolysis , Drosophila melanogaster/metabolism , Unfolded Protein Response , Ubiquitination , Cell Movement , Drosophila/metabolism
4.
Chemosphere ; 355: 141803, 2024 May.
Article in English | MEDLINE | ID: mdl-38554867

ABSTRACT

Swine farming produces large quantities of nutrient-rich wastewater, which often contains metals such as Cu and Zn, used as feed additives for pigs. These metals must be removed from the wastewater before discharge but their retention in the biomass can limit its subsequent utilization. Photobioreactors are a very promising alternative for swine wastewater treatment, as the consortium of microalgae and bacteria growing symbiotically in these reactors allows high nutrient and metal removal efficiency at moderate costs. This work studies the mechanisms of removal of Cu(II) and Zn(II) by the two types of microorganisms growing in these photobioreactors. A microalga commonly used in wastewater treatment (Scenedesmus almeriensis) and an activated sludge were kept in contact with synthetic wastewater containing 100 mg/L of Cu and Zn. After 72 h, Scenedesmus almeriensis removed 43% of Cu and 45% of Zn, while activated sludge removed 78% of Cu and 96% of Zn. Single and sequential extractions of the biomasses using different extracting reagents revealed that biosorption on protonable groups is the dominant removal mechanisms. Mild reagents solubilized 69% of Cu and 94% of Zn from the microalgae and 76% of Cu and 93% of Zn from the activated sludge. Low metal concentrations in the oxidizable and residual fractions evidenced minimal bioaccumulation inside the cells. FTIR and ESEM-EDX analysis confirmed biosorption by ion exchange and complexation as the main metal remediation mechanisms. The weak bonds of the biosorbed Cu and Zn ions are beneficial for the valorization of biomass and the obtaining of safe bioproducts.


Subject(s)
Metals, Heavy , Microalgae , Animals , Swine , Copper/analysis , Zinc/analysis , Wastewater , Sewage/chemistry , Metals , Bacteria , Nutrients/analysis , Biomass , Metals, Heavy/analysis
5.
Med. oral patol. oral cir. bucal (Internet) ; 29(2): e163-e171, Mar. 2024. ilus, tab
Article in English | IBECS | ID: ibc-231218

ABSTRACT

Background: The 8th edition of the American Joint Committee on Cancer (AJCC) classification has introduced two new parameters: depth of invasion (DOI) and extranodal extension (ENE). The aim of this systematic review was to determine whether this 8th edition referred to oral squamous cell carcinoma (OSCC) offers performance superior to that of the 7th edition in relation to overall survival (OS) and disease-specific survival (DSS). Material and Methods: The review was carried out following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines. The PubMed (MEDLINE), Scopus and Cochrane Library databases were searched covering the period up until April 7th, 2022.Results: Thirteen retrospective cohort studies were finally included. The introduction of DOI and ENE in the 8th edition of the AJCC classification resulted in improved prognostic performance of the classification. Conclusions: Patients with OSCC can be better classified in relation to OS and DSS, while maintaining the simplicity and ease of use of the classification. This allows more appropriate treatment protocols to be applied and affords a better estimation of the prognosis of each patient.(AU)


Subject(s)
Humans , Male , Female , Mouth Neoplasms , Squamous Cell Carcinoma of Head and Neck , Prognosis , Neoplasm Staging , Head and Neck Neoplasms , Retrospective Studies , United States , Oral Medicine , Pathology, Oral , Oral Health
6.
Med. oral patol. oral cir. bucal (Internet) ; 29(2): e172-e179, Mar. 2024. ilus, tab, graf
Article in English | IBECS | ID: ibc-231219

ABSTRACT

Background: Immediate loading of dental implants is considered an excellent option to reestablish function and aesthetics in a short period of time, thereby reducing the psychological impact of edentulism. The aim of this study was to describe the incidence of complications in immediately loaded implant-supported single or partial maxillary provisional rehabilitations; to assess changes in patient quality of life (QoL); to evaluate patient overall satisfaction; and to determine whether the occurrence of complications affects these outcomes. Material and Methods: Patients requiring partial rehabilitation with implants in the maxilla were included in a prospective cohort study. In all cases, implant-based restoration with an immediate loading protocol was indicated. A provisional restoration was placed within 72 hours after implant placement. Patient QoL was measured at the first appointment and just before placing the final restoration, using two validated questionnaires. All mechanical and biological complications occurring up until placement of the final restoration were documented. A descriptive and bivariate analysis of the data was performed. Results: Thirty-five patients with 40 prostheses supported by 60 implants were analyzed. Three implant failures were observed, yielding a 95% survival rate. Five provisional prosthesis fractures and two prosthetic screw loosenings were recorded in four patients. A significant reduction in OHIP-14 score was observed. Likewise, significant differences were found in the results of the QoLFAST-10, with a mean difference in score of 7.3 between the initial and final evaluation. Conclusions: Patients receiving immediately loaded implant-supported single or partial maxillary provisional rehabilitations seem to have a low risk of developing early mechanical (13.3%) or biological complications (5%)...(AU)


Subject(s)
Humans , Male , Female , Quality of Life , Dental Implants , Dental Implantation, Endosseous/methods , Esthetics, Dental , Maxilla/surgery , Immediate Dental Implant Loading , Cohort Studies , Prospective Studies , Oral Medicine , Oral Health , Pathology, Oral , Patient Satisfaction , Mouth Rehabilitation
7.
Sci Total Environ ; 922: 171215, 2024 Apr 20.
Article in English | MEDLINE | ID: mdl-38428611

ABSTRACT

Exposure to heat poses a pressing challenge in cities, with uneven health and environmental impacts across the urban fabric. To assess disparities in heat vulnerability and its environmental justice implications, we model supply-demand mismatches for the ecosystem service (ES) urban temperature regulation. We integrated remote sensing, health, and socio-demographic data with Artificial Intelligence for Environment and Sustainability (ARIES) and geographical information system tools. We computed composite indicators at the census tract level for urban cooling supply, and vulnerability to heat as a measure of demand. We do so in the context of the mid-size city of Vitoria-Gasteiz, Basque Country (Europe). We mapped relative mismatches after identifying and analysed their relationship with socio-demographic and health factors. Our findings show disparities in heat vulnerability, with increased exposure observed among socio-economically disadvantaged communities, the elderly, and people with health issues. Areas associated with higher income levels show lower ES mismatches, indicating higher temperature regulation supply and reduced heat vulnerability. The results point at the need for nature-based heat mitigation interventions that especially focus on the more socio-economically disadvantaged communities.


Subject(s)
Ecosystem , Hot Temperature , Humans , Aged , Artificial Intelligence , Cities , Cold Temperature
8.
Biomimetics (Basel) ; 9(1)2024 Jan 22.
Article in English | MEDLINE | ID: mdl-38275459

ABSTRACT

(1) Background: The aim was to perform a literature review on customized subperiosteal implants (CSIs) and provide clinical guidelines based on the results of an expert consensus meeting held in 2023. (2) Methods: A literature search was performed in Pubmed (MEDLINE) in July 2023, including case series and cohort studies with a minimum follow-up of 6 months that analyzed totally or partially edentulous patients treated with CSIs. Previously, an expert consensus meeting had been held in May 2023 to establish the most relevant clinical guidelines. (3) Results: Six papers (four case series and two retrospective cohort studies) were finally included in the review. Biological and mechanical complication rates ranged from 5.7% to 43.8% and from 6.3% to 20%, respectively. Thorough digital planning to ensure the passive fit of the CSI is mandatory to avoid implant failure. (4) Conclusions: CSIs are a promising treatment option for rehabilitating edentulous patients with atrophic jaws; they seem to have an excellent short-term survival rate, a low incidence of major complications, and less morbidity in comparison with complex bone grafting procedures. As the available data on the use of CSIs are very scarce, it is not possible to establish clinical recommendations based on scientific evidence.

9.
J Clin Med ; 13(2)2024 Jan 22.
Article in English | MEDLINE | ID: mdl-38276138

ABSTRACT

BACKGROUND: Coronary CT angiography (CCTA) may detect coronary artery disease (CAD) in transcatheter aortic valve implantation (TAVI) patients and may obviate invasive coronary angiography (ICA) in selected patients. We assessed the diagnostic accuracy of CCTA for detecting CAD in TAVI patients based on published data. METHODS: Meta-analysis and meta-regression were performed based on a comprehensive electronic search, including relevant studies assessing the diagnostic accuracy of CCTA in the setting of TAVI patients compared to ICA. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), were calculated on a patient and per segment level. RESULTS: Overall, 27 studies (total of 7458 patients) were included. On the patient level, the CCTA's pooled sensitivity and NPV were 95% (95% CI: 93-97%) and 97% (95% CI: 95-98%), respectively, while the specificity and PPV were at 73% (95% CI: 62-82%) and 64% (95% CI: 57-71%), respectively. On the segmental coronary vessel level, the sensitivity and NPV were 90% (95% CI: 79-96%) and 98% (95% CI: 97-99%). CONCLUSIONS: This meta-analysis highlights CCTA's potential as a first-line diagnostic tool although its limited PPV and specificity may pose challenges when interpreting heavily calcified arteries. This study underscores the need for further research and protocol standardization in this area.

10.
Eur J Dent Educ ; 28(1): 267-274, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37649221

ABSTRACT

INTRODUCTION: An evaluation was made of the psychometric properties of a Spanish version of the Consultation and Relational Empathy Measure (CARE) to assess relational empathy in undergraduate dental students. In addition, the influence of demographic, socio-economic and consultation-related factors upon the degree of perceived empathy and overall satisfaction was studied. MATERIALS AND METHODS: A cross-sectional study was carried out in patients seen in the Oral Surgery Unit by fourth year dental students. Dentists, specialized translators and psychologists developed the translation of the questionnaire. After a pilot test, a convenience sample of patients was included. Construct validity was tested by factor analysis using principal component analysis with varimax rotation and Kaiser standardization, and internal consistency was assessed by Cronbach's α. RESULTS: Two pilot tests were carried out with a panel of experts until the final version of the questionnaire was established. In the validation stage, 191 patients participated (92 men and 99 women), with a mean age of 52.5 ± 17 years. The mean score of the CARE measure was 47.2 ± 4.4, and 57.6% of the patients (n = 110) reported the maximum score on the questionnaire. The final version showed a 1-factor solution explaining 68.6% of the total variance, with excellent final internal consistency (α = 93.4%). CONCLUSION: The Spanish version of the CARE measure affords high reliability and validity in assessing relational empathy in dental students. Perceived empathy is related to overall satisfaction. Patient demographics and the number of visits do not influence perceived empathy.


Subject(s)
Empathy , Students, Dental , Male , Humans , Female , Adult , Middle Aged , Aged , Cross-Sectional Studies , Reproducibility of Results , Education, Dental , Psychometrics , Surveys and Questionnaires , Referral and Consultation
11.
Proc Natl Acad Sci U S A ; 120(52): e2310221120, 2023 Dec 26.
Article in English | MEDLINE | ID: mdl-38109551

ABSTRACT

The 21kD GTPase Rac is an evolutionarily ancient regulator of cell shape and behavior. Rac2 is predominantly expressed in hematopoietic cells where it is essential for survival and motility. The hyperactivating mutation Rac2E62K also causes human immunodeficiency, although the mechanism remains unexplained. Here, we report that in Drosophila, hyperactivating Rac stimulates ovarian cells to cannibalize neighboring cells, destroying the tissue. We then show that hyperactive Rac2E62K stimulates human HL60-derived macrophage-like cells to engulf and kill living T cell leukemia cells. Primary mouse Rac2+/E62K bone-marrow-derived macrophages also cannibalize primary Rac2+/E62K T cells due to a combination of macrophage hyperactivity and T cell hypersensitivity to engulfment. Additionally, Rac2+/E62K macrophages non-autonomously stimulate wild-type macrophages to engulf T cells. Rac2E62K also enhances engulfment of target cancer cells by chimeric antigen receptor-expressing macrophages (CAR-M) in a CAR-dependent manner. We propose that Rac-mediated cell cannibalism may contribute to Rac2+/E62K human immunodeficiency and enhance CAR-M cancer immunotherapy.


Subject(s)
Immunologic Deficiency Syndromes , Neoplasms , Receptors, Chimeric Antigen , Animals , Mice , Humans , rac GTP-Binding Proteins/genetics , rac GTP-Binding Proteins/metabolism , rac1 GTP-Binding Protein/metabolism , Cannibalism , Macrophages/metabolism , Immunologic Deficiency Syndromes/genetics , Cell Death
12.
Ecol Lett ; 26(12): 2098-2109, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37847674

ABSTRACT

We tested the idea that functional trade-offs that underlie species tolerance to drought-driven shifts in community composition via their effects on demographic processes and subsequently on shifts in species' abundance. Using data from 298 tree species from tropical dry forests during the extreme ENSO-2015, we scaled-up the effects of trait trade-offs from individuals to communities. Conservative wood and leaf traits favoured slow tree growth, increased tree survival and positively impacted species abundance and dominance at the community-level. Safe hydraulic traits, on the other hand, were related to demography but did not affect species abundance and communities. The persistent effects of the conservative-acquisitive trade-off across organizational levels is promising for generalization and predictability of tree communities. However, the safety-efficient trade-off showed more intricate effects on performance. Our results demonstrated the complex pathways in which traits scale up to communities, highlighting the importance of considering a wide range of traits and performance processes.


Subject(s)
Droughts , Tropical Climate , Humans , Forests , Trees/physiology , Wood , Plant Leaves
13.
J Cell Biol ; 222(11)2023 11 06.
Article in English | MEDLINE | ID: mdl-37747450

ABSTRACT

Src family kinases (SFKs) are evolutionarily conserved proteins acting downstream of receptors and regulating cellular processes including proliferation, adhesion, and migration. Elevated SFK expression and activity correlate with progression of a variety of cancers. Here, using the Drosophila melanogaster border cells as a model, we report that localized activation of a Src kinase promotes an unusual behavior: engulfment of one cell by another. By modulating Src expression and activity in the border cell cluster, we found that increased Src kinase activity, either by mutation or loss of a negative regulator, is sufficient to drive one cell to engulf another living cell. We elucidate a molecular mechanism that requires integrins, the kinases SHARK and FAK, and Rho family GTPases, but not the engulfment receptor Draper. We propose that cell cannibalism is a result of aberrant phagocytosis, where cells with dysregulated Src activity fail to differentiate between living and dead or self versus non-self, thus driving this malignant behavior.


Subject(s)
Cytophagocytosis , Drosophila melanogaster , src-Family Kinases , Animals , Drosophila melanogaster/genetics , src-Family Kinases/genetics
14.
J Mycol Med ; 33(3): 101412, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37451067

ABSTRACT

Onychomycosis is the most prevalent nail ailment in adults, accounting for 50% of all nail infections. Dermatophyte fungi are the primary cause, but non-dermatophyte molds (NDM) and yeasts can also cause onychomycosis. It remains important to precisely determine the fungal cause of onychomycosis since the response to current treatments may vary between fungal classes. Real-time polymerase chain reaction (qPCR) has become a widespread tool for detecting fungal organisms for diagnosis due to its sensitivity and ability to detect down to the species level. This retrospective study aims to evaluate the qPCR Onycho+ test for dermatophyte detection using remnants of toenails from a cohort of patients from Puerto Rico.  Two hundred forty-two toenail samples submitted for histological examination via Periodic acid Schiff (PAS) staining for suspected onychomycosis were analyzed by the Onycho+ test and Sanger sequencing of the internal transcribed spacer (ITS-2). Compared to the gold standard Sanger sequencing method, the Onycho+ test reported an agreement of 91.39%, a sensitivity of 100% and a specificity of 84.5% in detecting dermatophytes, superior to the histology method which had a 69.53% agreement, 85.1% sensitivity and 57.1% specificity. The distribution of fungal organisms detected in this cohort shows a dermatophyte majority but a higher-than-expected proportion of NDMs. Nails negative for the Onycho+ test and positive for histology were mostly NDMs. This study demonstrates that the clinical performance of the Onycho+ test is superior to histology in detecting dermatophytes and that a combination of Onycho+ and histology can result in a higher clinical accuracy.


Subject(s)
Arthrodermataceae , Onychomycosis , Adult , Humans , Onychomycosis/diagnosis , Onychomycosis/epidemiology , Onychomycosis/microbiology , Retrospective Studies , Puerto Rico/epidemiology , Nails/microbiology , Yeasts , Arthrodermataceae/genetics
15.
Rev. Fund. Educ. Méd. (Ed. impr.) ; 26(supl.1): S1-S89, Juli. 2023. tab, graf
Article in Spanish | IBECS | ID: ibc-226597

ABSTRACT

Introducción: Se trata de analizar el impacto de una secuencia formativa en la autopercepción del alumnado sobre las habilidades comunicativas. Secundariamente, se pretende conocer el grado de satisfacción del alumnado en relación con las actividades propuestas. Mètodos: Es un estudio cuasi experimental realizado sobre cuatro de los subgrupos de prácticas de la asignatura obligatoria de cuarto curso Cirugía Bucal Clínica e Implantología. Dos de los subgrupos recibieron una secuencia formativa específica para la mejora de sus habilidades comunicativas (n = 40) y los otros dos actuaron como controles (n = 47). Al inicio y al final del estudio, los participantes respondieron el cuestionario validado SE-12 de autopercepción sobre comunicación odontólogo-paciente. La estrategia evaluativa fue continua y formativa. Se analizaron y compararon las puntuaciones de los distintos indicadores e instrumentos de evaluación empleados.Resultados: A excepción de un alumno del grupo de control, todos los estudiantes participaron de forma activa en el proyecto. En ambos grupos se observó una mejora estadísticamente significativa en la percepción de las habilidades comunicativas (p < 0,001). No obstante, los alumnos asignados al grupo experimental percibieron una mejora significativamente mayor (diferencia de medias = 0,96 puntos; intervalo de confianza al 95% = 0,66-1,27; p < 0,001). Los alumnos valoraron la secuencia con un 8,56 (desviación estándar = 1,14).Conclusiones: La implementación de la secuencia formativa produjo una mejora en la percepción que tienen los estudiantes sobre sus habilidades comunicativas. Es necesaria la inclusión de programas longitudinales de formación en comunicación en los planes de estudio para acreditar la consecución de las competencias comunicativas.(AU)


Introduction: To analyze the impact of a training-learning sequence on students' self-perception of communication skills. Secondarily, to know the degree of student satisfaction in relation to the proposed activities.Methods: A quasi-experimental study was carried out on four of the clinical practice subgroups of Clinical Oral Surgery and Implantology (fourth year of study). Two of the subgroups received a specific training-learning sequence to improve their communication skills (n = 40) and the other two served as controls (n = 47). At the beginning and end of the study, the participants answered the validated SE-12 self-perception questionnaire on dentist-patient communication. The evaluation strategy was continuous and formative. The scores of the different indicators and evaluation instruments used were analyzed and compared.Results: Except for one student in the control group, all students participated actively in the project. In both groups, a statistically significant improvement was observed in the perception of communication skills (p < 0.001). However, the students assigned to the experimental group perceived a significantly greater improvement (difference in means = 0.96 points; 95% confidence interval = 0.66-1.27; p < 0.001). The students valued the training-learning sequence with an 8.56 (standard deviation = 1.14).Conclusions: The implementation of the training-learning sequence produced an improvement in the perception that students have about their communication skills. It is necessary to include longitudinal training programs in communication in the curricula to prove the achievement of communication skills competences.(AU)


Subject(s)
Humans , Male , Female , Health Communication , Students, Dental , Dentists , Physician-Patient Relations , Communication , Education, Medical , Self Concept , Case-Control Studies , Learning , Simulation Exercise
16.
bioRxiv ; 2023 May 22.
Article in English | MEDLINE | ID: mdl-37292980

ABSTRACT

Proteotoxic stress drives numerous degenerative diseases. In response to misfolded proteins, cells adapt by activating the unfolded protein response (UPR), including endoplasmic reticulum-associated protein degradation (ERAD). However persistent stress triggers apoptosis. Enhancing ERAD is a promising therapeutic approach for protein misfolding diseases. From plants to humans, loss of the Zn2+ transporter ZIP7 causes ER stress, however the mechanism is unknown. Here we show that ZIP7 enhances ERAD and that cytosolic Zn2+ is limiting for deubiquitination of client proteins by the Rpn11 Zn2+ metalloproteinase as they enter the proteasome in Drosophila and human cells. ZIP7 overexpression rescues defective vision caused by misfolded rhodopsin in Drosophila. Thus ZIP7 overexpression may prevent diseases caused by proteotoxic stress, and existing ZIP inhibitors may be effective against proteasome-dependent cancers.

17.
Acta Pharm Sin B ; 13(1): 82-99, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36815042

ABSTRACT

Opioids are the most effective painkillers, but their benefit-risk balance often hinder their therapeutic use. WLB-73502 is a dual, bispecific compound that binds sigma-1 (S1R) and mu-opioid (MOR) receptors. WLB-73502 is an antagonist at the S1R. It behaved as a partial MOR agonist at the G-protein pathway and produced no/unsignificant ß-arrestin-2 recruitment, thus demonstrating low intrinsic efficacy on MOR at both signalling pathways. Despite its partial MOR agonism, WLB-73502 exerted full antinociceptive efficacy, with potency superior to morphine and similar to oxycodone against nociceptive, inflammatory and osteoarthritis pain, and superior to both morphine and oxycodone against neuropathic pain. WLB-73502 crosses the blood-brain barrier and binds brain S1R and MOR to an extent consistent with its antinociceptive effect. Contrary to morphine and oxycodone, tolerance to its antinociceptive effect did not develop after repeated 4-week administration. Also, contrary to opioid comparators, WLB-73502 did not inhibit gastrointestinal transit or respiratory function in rats at doses inducing full efficacy, and it was devoid of proemetic effect (retching and vomiting) in ferrets at potentially effective doses. WLB-73502 benefits from its bivalent S1R antagonist and partial MOR agonist nature to provide an improved antinociceptive and safety profile respect to strong opioid therapy.

18.
PLoS One ; 18(2): e0281348, 2023.
Article in English | MEDLINE | ID: mdl-36827966

ABSTRACT

This article describes the adaptation of a non-spatial model of pastureland dynamics, including vegetation life cycle, livestock management and nitrogen cycle, for use in a spatially explicit and modular modelling platform (k.LAB) dedicated to make data and models more interoperable. The aim is to showcase to the social-ecological modelling community the delivery of an existing, monolithic model, into a more modular, transparent and accessible approach to potential end users, regional managers, farmers and other stakeholders. This also allows better usability and adaptability of the model beyond its originally intended geographical scope (the Cantabrian Region in the North of Spain). The original code base (written in R in 1,491 lines of code divided into 13 files) combines several algorithms drawn from the literature in an opaque fashion due to lack of modularity, non-semantic variable naming and implicit assumptions. The spatiotemporal rewrite is structured around a set of 10 namespaces called PaL (Pasture and Livestock), which includes 198 interoperable and independent models. The end user chooses the spatial and temporal context of the analysis through an intuitive web-based user interface called k.Explorer. Each model can be called individually or in conjunction with the others, by querying any PaL-related concepts in a search bar. A scientific dataflow and a provenance diagram are produced in conjunction with the model results for full transparency. We argue that this work demonstrates key steps needed to create more Findable, Accessible, Interoperable and Reusable (FAIR) models beyond the selected example. This is particularly essential in environments as complex as agricultural systems, where multidisciplinary knowledge needs to be integrated across diverse spatial and temporal scales in order to understand complex and changing problems.


Subject(s)
Algorithms , Livestock , Animals , Spain , Models, Theoretical
19.
Polymers (Basel) ; 15(3)2023 Jan 21.
Article in English | MEDLINE | ID: mdl-36771859

ABSTRACT

Eliminating warpage in injection molded polymeric parts is one of the most important problems in the injection molding industry today. This situation is critical in geometries that are particularly susceptible to warping due to their geometric features, and this occurs with topologies of great length and slenderness with high changes in thickness. These features are, in these special geometries, impossible to manufacture with traditional technologies to meet the dimensional and sustainable requirements of the industry. This paper presents an innovative green conformal cooling system that is specifically designed for parts with slender geometric shapes that are highly susceptible to warping. Additionally, the work presented by the authors investigates the importance of using highly conductive inserts made of steel alloys in combination with the use of additively manufactured conformal channels for reducing influential parameters, such as warpage, cooling time, and residual stresses in the complex manufacturing of long and slender parts. The results of this real industrial case study indicated that the use of conformal cooling layouts decreased the cycle time by 175.1 s-66% below the current cooling time; the temperature gradient by 78.5%-specifically, 18.16 °C; the residual stress by 39.78 MPa-or 81.88%; and the warpage by 6.9 mm-or 90.5%. In this way, it was possible to achieve a final warping in the complex geometry studied of 0.72 mm, which was under the maximum value required at the industrial level of 1 mm. The resulting values obtained by the researchers present a turning point from which the manufacturing and sustainability in the injection molding of said plastic geometries is possible, and they take into account that the geometric manufacturing features analyzed will present a great demand in the coming years in the auto parts manufacturing industry.

20.
Eur Heart J ; 44(34): 3250-3260, 2023 09 07.
Article in English | MEDLINE | ID: mdl-36747318

ABSTRACT

AIMS: To provide population-based data on the prevalence and clinical significance of immune deficiency syndromes (IDS) associated with congenital heart disease (CHD). METHODS AND RESULTS: Utilizing administrative German Health System data the prevalence of increased susceptibility to infection (ISI) or confirmed IDS was assessed in CHD patients and compared with an age-matched non-congenital control group. Furthermore, the prognostic significance of IDS was assessed using all-cause mortality and freedom from emergency hospital admission. A total of 54 449 CHD patients were included. Of these 14 998 (27.5%) had ISI and 3034 (5.6%) had a documented IDS (compared with 2.9% of the age-matched general population). During an observation period of 394 289 patient-years, 3824 CHD patients died, and 31 017 patients experienced a combined event of all-cause mortality or emergency admission. On multivariable Cox proportional-hazard analysis, the presence of ISI [hazard ratio (HR): 2.14, P < 0.001] or documented IDS (HR: 1.77, P = 0.035) emerged as independent predictors of all-cause mortality. In addition, ISI and confirmed IDS were associated with a significantly higher risk of emergency hospital admission (P = 0.01 for both on competing risk analysis) during follow-up. CONCLUSION: Limited immune competence is common in CHD patients and associated with an increased risk of morbidity and mortality. This highlights the need for structured IDS screening and collaboration with immunology specialists as immunodeficiency may be amenable to specific therapy. Furthermore, studies are required to assess whether IDS patients might benefit from intensified antibiotic shielding or tailored prophylaxis.


Subject(s)
Heart Defects, Congenital , Hospitalization , Humans , Risk Factors , Heart Defects, Congenital/complications , Heart Defects, Congenital/epidemiology , Risk Assessment , Proportional Hazards Models
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