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1.
Sci Total Environ ; 945: 174030, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38885698

RESUMO

Remediation strategies for metal(loid)-polluted soils vary among the wide range of approaches, including physical, chemical, and biological remediation, or combinations of these. In this study, we assessed the effectiveness of a set of soil remediation treatments based on the combined application of inorganic (marble sludge) and organic amendments (vermicompost, and dry olive residue [DOR] biotransformed by the saprobic fungi Coriolopsis rigida and Coprinellus radians) and inoculation with arbuscular mycorrhizal fungi (AMFs) (Rhizophagus irregularis and Rhizoglomus custos). The treatments were applied under greenhouse conditions to soil residually polluted by potentially toxic elements (PTEs) (Pb, As, Zn, Cu, Cd, and Sb), and wheat was grown in the amended soils to test the effectiveness of the treatments in reducing soil toxicity and improving soil conditions and plant performance. Therefore, we evaluated the influence of the treatments on the main soil properties and microbial activities, as well as on PTE availability and bioaccumulation in wheat plants. Overall, the results showed a positive influence of all treatments on the main soil properties. Treatments consisting of a combination of marble and organic amendments, especially biotransformed DOR amendments, showed the greatest effectiveness in improving the soil biological status, promoting plant growth and survival, and reducing PTE availability and plant uptake. Furthermore, AMF inoculation further enhanced the efficacy of DOR amendments by promoting the immobilization of PTEs in soil and stimulating the phytostabilization mechanisms induced by AMFs, thus playing an important bioprotective role in plants. Therefore, our results highlight that biotransformed DOR may represent an efficient product for use as a soil organic amendment when remediating metal(loid)-polluted soils, and that its application in combination with AMFs may represent a promising sustainable bioremediation strategy for recovering soil functions and reducing toxicity in polluted areas.


Assuntos
Biodegradação Ambiental , Micorrizas , Microbiologia do Solo , Poluentes do Solo , Poluentes do Solo/metabolismo , Micorrizas/fisiologia , Micorrizas/metabolismo , Solo/química , Metais Pesados/metabolismo , Triticum/metabolismo , Simbiose
2.
Rev Lat Am Enfermagem ; 32: e4140, 2024.
Artigo em Inglês, Espanhol, Português | MEDLINE | ID: mdl-38865553

RESUMO

OBJECTIVE: to describe and explore the relationship of loneliness, anxiety and depression with adoption of the caregiver role among individuals caring for people with chronic diseases in Colombia. METHODS: this was an exploratory and cross-sectional study involving 960 primary caregivers of individuals with chronic diseases. We applied the Caregiver Role Adoption Scale, the University of California at Los Angeles Loneliness Scale, and the Anxiety and Depression Scale. Principal component and multiple correspondence analyses were performed for clustering. RESULTS: among the participating caregivers, 40.8% reported experiencing depression, 59% reported anxiety, 54.6% reported moderate to severe loneliness, and 88.6% reported satisfactory adoption of the caregiver role. Caregivers who presented basic or insufficient role adoption levels tended to have higher scores for anxiety, depression and loneliness. CONCLUSION: adoption of the caregiver role is a mediator in the anxiety, depression and loneliness levels among caregivers. Strategies aimed at supporting caregivers should include training for the caregiver role to mitigate the negative impacts of anxiety, depression and loneliness. (1) More than half of the caregivers reported moderate or severe anxiety and loneliness. (2) Caregivers with low role adoption levels presented more anxiety, depression and loneliness. (3) Satisfactory adoption of the caregiver role reduces anxiety, depression and loneliness. (4) Role adoption should be intervened to reduce the impact on caregivers' mental health.


Assuntos
Ansiedade , Cuidadores , Depressão , Solidão , Humanos , Cuidadores/psicologia , Estudos Transversais , Masculino , Solidão/psicologia , Feminino , Depressão/epidemiologia , Depressão/psicologia , Pessoa de Meia-Idade , Doença Crônica/psicologia , Ansiedade/epidemiologia , Adulto , Idoso , Papel (figurativo) , Adulto Jovem
3.
Front Med (Lausanne) ; 11: 1338542, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38504911

RESUMO

Introduction: Prevalence and mortality of the acute respiratory distress syndrome (ARDS) in intensive care units (ICU) are unacceptably high. There is scarce literature on post-operative sepsis-induced ARDS despite that sepsis and major surgery are conditions associated with ARDS. We aimed to examine the impact of post-operative sepsis-induced ARDS on 60-day mortality. Methods: We performed a secondary analysis of a prospective observational study in 454 patients who underwent major surgery admitted into a single ICU. Patients were stratified in two groups depending on whether they met criteria for ARDS. Primary outcome was 60-day mortality of post-operative sepsis-induced ARDS. Secondary outcome measures were potential risk factors for post-operative sepsis-induced ARDS, and for 60-day mortality. Results: Higher SOFA score (OR 1.1, 95% CI 1.0-1.3, p = 0.020) and higher lactate (OR 1.9, 95% CI 1.2-2.7, p = 0.004) at study inclusion were independently associated with ARDS. ARDS patients (n = 45) had higher ICU stay [14 (18) vs. 5 (11) days, p < 0.001] and longer need for mechanical ventilation [6 (14) vs. 1 (5) days, p < 0.001] than non-ARDS patients (n = 409). Sixty-day mortality was higher in ARDS patients (OR 2.7, 95% CI 1.1-6.3, p = 0.024). Chronic renal failure (OR 4.0, 95% CI 1.2-13.7, p = 0.026), elevated lactate dehydrogenase (OR 1.7, 95% CI 1.1-2.7, p = 0.015) and higher APACHE II score (OR 2.7, 95% CI 1.3-5.4, p = 0.006) were independently associated with 60-day mortality. Conclusion: Post-operative sepsis-induced ARDS is associated with higher 60-day mortality compared to non-ARDS post-operative septic patients. Post-operative septic patients with higher severity of illness have a greater risk of ARDS and worse outcomes. Further investigation is needed in post-operative sepsis-induced ARDS to prevent ARDS.

4.
Eur J Clin Invest ; 54(6): e14191, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38440843

RESUMO

BACKGROUND: Genetic diagnosis of inborn errors of immunity (IEI) is complex due to the large number of genes involved and their molecular features. Missense variants have been reported as the most common cause of IEI. However, the frequency of copy number variants (CNVs) may be underestimated since their detection requires specific quantitative techniques. At this point, the use of Next Generation Sequencing (NGS) is acquiring relevance. METHODS: In this article, we present our experience in the genetic diagnosis of IEI based on three diagnostic algorithms that allowed the detection of single nucleotide variants (SNVs) and CNVs. Following this approximation, 703 index cases were evaluated between 2014 and 2021. Sanger sequencing, MLPA, CGH array, breakpoint spanning PCR or a customized NGS-based multigene-targeted panel were performed. RESULTS: A genetic diagnosis was reached in 142 of the 703 index cases (20%), 19 of them presented deletions as causal variants. Deletions were also detected in 5 affected relatives and 16 healthy carriers during the family studies. Additionally, we compile, characterize and present all the CNVs detected by our diagnostic algorithms, representing the largest cohort of deletions related to IEI to date. Furthermore, three bioinformatic tools (LACONv, XHMM, VarSeq™) based on NGS data were evaluated. VarSeq™ was the most sensitive and specific bioinformatic tool; detecting 21/23 (91%) deletions located in captured regions. CONCLUSION: Based on our results, we propose a strategy to guide the molecular diagnosis that can be followed by expert and non-expert centres in the field of IEI.


Assuntos
Variações do Número de Cópias de DNA , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Variações do Número de Cópias de DNA/genética , Algoritmos , Masculino , Feminino , Polimorfismo de Nucleotídeo Único , Criança , Mutação de Sentido Incorreto/genética
5.
Surg Oncol ; 52: 102039, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38301449

RESUMO

BACKGROUND AND OBJECTIVES: Recurrent isolated pancreatic metastasis from Renal Cell Carcinoma (RCC) after pancreatic resection is rare. The purpose of our study is to describe a series of cases of relapse of pancreatic metastasis from renal cancer in the pancreatic remnant and its surgical treatment with a repeated pancreatic resection, and to analyse the results of both overall and disease-free survival. METHODS: Multicenter retrospective study of patients undergoing pancreatic resection for RCC pancreatic metastases, from January 2010 to May 2020. Patients were grouped into two groups depending on whether they received a single pancreatic resection (SPS) or iterative pancreatic resection. Data on short and long-term outcome after pancreatic resection were collected. RESULTS: The study included 131 pancreatic resections performed in 116 patients. Thus, iterative pancreatic surgery (IPS) was performed in 15 patients. The mean length of time between the first pancreatic surgery and the second was 48.9 months (95 % CI: 22.2-56.9). There were no differences in the rate of postoperative complications. The DFS rates at 1, 3 and 5 years were 86 %, 78 % and 78 % vs 75 %, 50 % and 37 % in the IPS and SPS group respectively (p = 0.179). OS rates at 1, 3, 5 and 7 years were 100 %, 100 %, 100 % and 75 % in the IPS group vs 95 %, 85 %, 80 % and 68 % in the SPS group (p = 0.895). CONCLUSION: Repeated pancreatic resection in case of relapse of pancreatic metastasis of RCC in the pancreatic remnant is justified, since it achieves OS results similar to those obtained after the first resection.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Neoplasias Pancreáticas , Humanos , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Renais/patologia , Estudos Retrospectivos , Pancreatectomia/métodos , Neoplasias Pancreáticas/patologia , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Recidiva
6.
J Environ Manage ; 352: 120042, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38198843

RESUMO

An increasing number of countries and regions consider the bioeconomy transition a strategic policy priority. When approached through the lens of a circular economy perspective, investments in bioeconomy have the potential to enhance resource utilisation efficiency, preserve biodiversity and ecosystems, and foster sustainable development with low emissions. At the same time, if requirements and contextual factors of bioeconomy strategies are not formally analysed, bioeconomic investments might lead to unintended negative consequences. This paper proposes a decision support procedure to design, assess, prioritise, and monitor bioeconomy investments and policies. The flexibility and scalability of our decision support procedure is tested in Colombia to foster a regional and local transition to bioeconomy initiatives that consider the local capital assets and the stakeholders' views. The heterogeneous character of the Colombian environment, economy, society and culture represents an ideal condition to test the strength of the decision support procedure to promote bioeconomy in low and middle-income countries. Our empirical results highlight the benefit of adopting a formal assessment framework that includes strategic national indicators, regional features and stakeholders' views. In terms of the Colombian regional bioeconomy ambitions, we highlight the need for expanding knowledge hubs and participatory stakeholder networks and buttressing appropriate financial mechanisms.


Assuntos
Desenvolvimento Econômico , Ecossistema , Colômbia , Desenvolvimento Sustentável , Políticas
7.
Cir Esp (Engl Ed) ; 102(3): 158-173, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38242231

RESUMO

Faecal incontinence (FI) is a major health problem, both for individuals and for health systems. It is obvious that, for all these reasons, there is widespread concern for healing it or, at least, reducing as far as possible its numerous undesirable effects, in addition to the high costs it entails. There are different criteria for the diagnostic tests to be carried out and the same applies to the most appropriate treatment, among the numerous options that have proliferated in recent years, not always based on rigorous scientific evidence. For this reason, the Spanish Association of Coloproctology (AECP) proposed to draw up a consensus to serve as a guide for all health professionals interested in the problem, aware, however, that the therapeutic decision must be taken on an individual basis: patient characteristics/experience of the care team. For its development it was adopted the Nominal Group Technique methodology. The Levels of Evidence and Grades of Recommendation were established according to the criteria of the Oxford Centre for Evidence-Based Medicine. In addition, expert recommendations were added briefly to each of the items analysed.


Assuntos
Terapia por Estimulação Elétrica , Incontinência Fecal , Humanos , Terapia por Estimulação Elétrica/métodos , Incontinência Fecal/diagnóstico , Incontinência Fecal/terapia , Canal Anal , Medicina Baseada em Evidências
8.
Rev. latinoam. enferm. (Online) ; 32: e4140, 2024. tab, graf
Artigo em Inglês | LILACS-Express | LILACS, BDENF - Enfermagem | ID: biblio-1560142

RESUMO

Objective: to describe and explore the relationship of loneliness, anxiety and depression with adoption of the caregiver role among individuals caring for people with chronic diseases in Colombia. Methods: this was an exploratory and cross-sectional study involving 960 primary caregivers of individuals with chronic diseases. We applied the Caregiver Role Adoption Scale, the University of California at Los Angeles Loneliness Scale, and the Anxiety and Depression Scale. Principal component and multiple correspondence analyses were performed for clustering. Results: among the participating caregivers, 40.8% reported experiencing depression, 59% reported anxiety, 54.6% reported moderate to severe loneliness, and 88.6% reported satisfactory adoption of the caregiver role. Caregivers who presented basic or insufficient role adoption levels tended to have higher scores for anxiety, depression and loneliness. Conclusion: adoption of the caregiver role is a mediator in the anxiety, depression and loneliness levels among caregivers. Strategies aimed at supporting caregivers should include training for the caregiver role to mitigate the negative impacts of anxiety, depression and loneliness.


Objetivo: describir y explorar la relación de la soledad, la ansiedad y la depresión con la adopción del rol de cuidador entre personas que se ocupan de cuidar pacientes con enfermedades crónicas en Colombia. Métodos: se trató de un estudio exploratorio y transversal con la participación de 960 cuidadores principales de personas con enfermedades crónicas. Aplicamos la Escala de Adopción del Rol de Cuidador, la Escala de Soledad de la Universidad de California de Los Ángeles y la Escala de Ansiedad y Depresión. Se realizaron análisis de componentes principales y de correspondencia múltiple para el clustering . Resultados: el 40,8% de los cuidadores que participaron en el estudio informó padecer depresión, el 59% informó ansiedad, el 54,6% indicó soledad de moderada a grave y el 88,6% presentó adopción satisfactoria del rol de cuidador. Los cuidadores que presentaron los niveles básico o insuficiente en términos de adopción del rol tendieron a obtener puntuaciones de ansiedad, depresión y soledad más elevadas. Conclusión: adoptar el rol de cuidador es un mediador de los niveles de ansiedad, depresión y soledad entre los cuidadores. Las estrategias dirigidas a apoyar a los cuidadores deberían incluir preparación para dicho rol a fin de mitigar los efectos negativos de la ansiedad, la depresión y la soledad.


Objetivo: descrever e explorar a relação entre a solidão, a ansiedade e a depressão com a adoção do papel de cuidador entre os indivíduos que cuidam de pessoas com doenças crônicas na Colômbia. Método: trata-se de um estudo exploratório e transversal que envolveu 960 cuidadores primários de indivíduos com doenças crônicas. Foi aplicada a Escala de Adoção do Papel de Cuidador, a Escala de Solidão da Universidade da Califórnia em Los Angeles e a Escala de Ansiedade e Depressão. Foram realizadas análises de componentes principais e de correspondência múltipla para o agrupamento. Resultados: entre os cuidadores participantes, 40,8% relataram ter depressão, 59% relataram ansiedade, 54,6% relataram solidão moderada a grave e 88,6% relataram uma adoção satisfatória do papel de cuidador. Os cuidadores que apresentaram níveis básicos ou insuficientes de adoção do papel tenderam a ter pontuações mais elevadas de ansiedade, depressão e solidão. Conclusão: a adoção do papel de cuidador é um mediador nos níveis de ansiedade, depressão e solidão entre os cuidadores. As estratégias destinadas a apoiar os cuidadores devem incluir o treinamento para o papel de cuidador, a fim de atenuar os impactos negativos da ansiedade, da depressão e da solidão.

9.
Toxics ; 11(10)2023 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-37888704

RESUMO

This study evaluated the effectiveness of six Technosols designed for the remediation of polluted soils (PS) by metal(loid)s at physicochemical, biological, and ecotoxicological levels and at a microcosm scale. Technosols T1-T6 were prepared by combining PS with a mix of organic and inorganic wastes from mining, urban, and agro-industrial activities. After two months of surface application of Technosols on polluted soils, we analysed the soil properties, metal(loid) concentration in total, soluble and bioavailable fractions, soil enzymatic activities, and the growth responses of Trifolium campestre and Lactuca sativa in both the Technosols and the underlying polluted soils. All Technosols improved the unfavourable conditions of polluted soils by neutralising acidity, increasing the OC, reducing the mobility of most metal(loid)s, and stimulating both the soil enzymatic activities and growths of T. campestre and L. sativa. The origin of organic waste used in the Technosols strongly conditioned the changes induced in the polluted soils; in this sense, the Technosols composed of pruning and gardening vermicompost (T3 and T6) showed greater reductions in toxicity and plant growth than the other Technosols composed with different organic wastes. Thus, these Technosols constitute a potential solution for the remediation of persistent polluted soils that should be applied in large-scale and long-term interventions to reinforce their feasibility as a cost-effective ecotechnology.

10.
Trop Anim Health Prod ; 55(5): 308, 2023 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-37731011

RESUMO

Two experiments were conducted to evaluate the effect of intramuscular administration of minerals during a TAI program on the reproductive responses of lactating Angus cows. All cows (n=353) were subjected to a 9-day TAI program based on CIDR insertion plus injections of estradiol, cloprostenol, and eCG, and then TAI 48 h later. In experiment 1, two groups were randomly created, one control with a placebo injection (CON, n=109), and the second received 10 mL of Fosfosan® (MIN, n=172) on day 0 of the synchronization. Conception rate (66.9 vs. 55%) and estrus percentage (55.8 vs. 44%) were higher (P≤0.05) in MIN than in CON cows. Given these results, a second experiment was conducted randomly assigning the cows to two treatments (n=36 each): a single injection of 10 mL of Fosfosan® (MIN-O) on day 0 or two injections of 10 mL of Fosfosan® (MIN-T) on synchronization days 0 and 7. Four cows of each treatment were randomly selected to be scanned with transrectal ultrasound before and during the synchronization protocol to assess ovarian structures and cyclicity, and at day 39 post-TAI for pregnancy diagnosis. Also, blood samples were obtained for the determination of serum minerals and progesterone (P4) concentrations. The number of mineral injections did not affect conception rate (P≥0.1229) conception rate, serum mineral and P4 concentrations, number, and size of emerging follicles, or follicle size according to 1 to 4 classifications. The MIN-T promoted (P<0.05) earlier follicular wave emergence than MIN-O. However, MIN-O cows had a dominant follicle of 15.12 mm, which is more significant (P<0.05) than that in MIN-T cows (13.5 mm). In conclusion, providing a single mineral injection of Fosfosan® at the start of a TAI program is an excellent reproductive strategy in lactating Angus cows to improve the dominant follicle growth, estrus response, and conception rate.


Assuntos
Lactação , Ovário , Animais , Bovinos , Feminino , Gravidez , Suplementos Nutricionais , Inseminação Artificial/veterinária , Ovário/diagnóstico por imagem , Reprodução
11.
Hum Brain Mapp ; 44(16): 5294-5308, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37498048

RESUMO

The human brain is a complex network comprised of functionally and anatomically interconnected brain regions. A growing number of studies have suggested that empirical estimates of brain networks may be useful for discovery of biomarkers of disease and cognitive state. A prerequisite for realizing this aim, however, is that brain networks also serve as reliable markers of an individual. Here, using Human Connectome Project data, we build upon recent studies examining brain-based fingerprints of individual subjects and cognitive states based on cognitively demanding tasks that assess, for example, working memory, theory of mind, and motor function. Our approach achieves accuracy of up to 99% for both identification of the subject of an fMRI scan, and for classification of the cognitive state of a previously unseen subject in a scan. More broadly, we explore the accuracy and reliability of five different machine learning techniques on subject fingerprinting and cognitive state decoding objectives, using functional connectivity data from fMRI scans of a high number of subjects (865) across a number of cognitive states (8). These results represent an advance on existing techniques for functional connectivity-based brain fingerprinting and state decoding. Additionally, 16 different functional connectome (FC) matrix construction pipelines are compared in order to characterize the effects of different aspects of the production of FCs on the accuracy of subject and task classification, and to identify possible confounds.


Assuntos
Conectoma , Humanos , Conectoma/métodos , Reprodutibilidade dos Testes , Rede Nervosa/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Aprendizado de Máquina , Cognição
12.
Sci Rep ; 13(1): 12120, 2023 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-37495757

RESUMO

Acid mine drainage (AMD) poses serious consequences for human health and ecosystems. Novel strategies for its treatment involve the use of wastes. This paper evaluates the remediation potential of wastes from urban, mining and agro-industrial activities to address acidity and high concentrations of potentially toxic elements (PTE) in AMD. Samples of these waste products were spiked with an artificially prepared AMD, then pH, electrical conductivity (EC), and PTE concentrations in the leachates were measured. The artificial AMD obtained through oxidation of Aznalcóllar's tailing showed an ultra-acid character (pH - 2.89 ± 0.03) and extreme high electrical conductivity (EC - 3.76 ± 0.14 dS m-1). Moreover, most PTE were above maximum regulatory levels in natural and irrigation waters. Wastes studied had a very high acid neutralising capacity, as well as a strong capacity to immobilise PTE. Inorganic wastes, together with vermicompost from pruning, reduced most PTE concentrations by over 95%, while organic wastes retained between 50 and 95%. Thus, a wide range of urban, mining, and agro-industrial wastes have a high potential to be used in the treatment of AMD. This study provides valuable input for the development of new eco-technologies based on the combination of wastes (eg. Technosols, permeable reactive barriers) to remediate degraded environments.


Assuntos
Ecossistema , Poluentes Químicos da Água , Humanos , Mineração , Poluentes Químicos da Água/análise , Monitoramento Ambiental
14.
Am J Cardiol ; 200: 204-211, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37354778

RESUMO

There is limited data on new-generation stent outcomes in patients with previous coronary artery bypass graft (CABG) and the associated risk of gender and race/ethnicity is unclear. We investigated 1-year outcomes after platinum chromium everolimus-eluting stent implantation in a diverse population of men, women, and minorities with previous CABG pooled from the PLATINUM Diversity (NCT02240810) and PROMUS Element Plus (NCT01589978) registries. Our primary outcome was major adverse cardiac events (MACE), a composite of all-cause death, myocardial infarction (MI), and target vessel revascularization (TVR) at 1-year post percutaneous coronary intervention (PCI). Secondary end points included all-cause death, MI, TVR, target vessel failure, and stent thrombosis. A total of 4,175 patients were included in the analysis, including 1,858 women (44.5%), 1,057 minorities (25.3%), and 662 (15.9%) with previous CABG. Patients with previous CABG were older, included more men and White patients, and had more co-morbidities compared with patients without previous CABG. At 1 year, patients with previous CABG had a higher risk of MACE (12.6% vs 7.5%, hazard ratio 1.70, 95% confidence interval 1.32 to 2.19, p <0.001) and end points, including death/MI, TVR, and target vessel failure. After multivariate adjustment, no differences were observed in MACE (adjusted hazard ratio 1.11, 95% confidence interval 0.82 to 1.49, p = 0.506) or any secondary end points. No interaction was observed between previous CABG and gender or minority status. In conclusion, in a contemporary PCI population, patients with previous CABG remain at high risk for PCI because of their elevated risk profile. Previous CABG status was however not independently associated with worse outcomes after adjustment, nor was any interaction observed with gender or race/ethnicity.


Assuntos
Doença da Artéria Coronariana , Stents Farmacológicos , Infarto do Miocárdio , Intervenção Coronária Percutânea , Feminino , Humanos , Masculino , Ponte de Artéria Coronária/efeitos adversos , Doença da Artéria Coronariana/complicações , Stents Farmacológicos/efeitos adversos , Infarto do Miocárdio/epidemiologia , Intervenção Coronária Percutânea/efeitos adversos , Platina , Sistema de Registros , Fatores de Risco , Resultado do Tratamento , Estudos Clínicos como Assunto
15.
Hepatology ; 78(5): 1337-1351, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37021797

RESUMO

BACKGROUND AND AIMS: Paucity of intrahepatic bile ducts (BDs) is caused by various etiologies and often leads to cholestatic liver disease. For example, in patients with Alagille syndrome (ALGS), which is a genetic disease primarily caused by mutations in jagged 1 ( JAG1) , BD paucity often results in severe cholestasis and liver damage. However, no mechanism-based therapy exists to restore the biliary system in ALGS or other diseases associated with BD paucity. Based on previous genetic observations, we investigated whether postnatal knockdown of the glycosyltransferase gene protein O -glucosyltransferase 1 ( Poglut1) can improve the ALGS liver phenotypes in several mouse models generated by removing one copy of Jag1 in the germline with or without reducing the gene dosage of sex-determining region Y-box 9 in the liver. APPROACH AND RESULTS: Using an ASO established in this study, we show that reducing Poglut1 levels in postnatal livers of ALGS mouse models with moderate to profound biliary abnormalities can significantly improve BD development and biliary tree formation. Importantly, ASO injections prevent liver damage in these models without adverse effects. Furthermore, ASO-mediated Poglut1 knockdown improves biliary tree formation in a different mouse model with no Jag1 mutations. Cell-based signaling assays indicate that reducing POGLUT1 levels or mutating POGLUT1 modification sites on JAG1 increases JAG1 protein level and JAG1-mediated signaling, suggesting a likely mechanism for the observed in vivo rescue. CONCLUSIONS: Our preclinical studies establish ASO-mediated POGLUT1 knockdown as a potential therapeutic strategy for ALGS liver disease and possibly other diseases associated with BD paucity.


Assuntos
Síndrome de Alagille , Glicosiltransferases , Fígado , Oligonucleotídeos Antissenso , Animais , Camundongos , Síndrome de Alagille/genética , Síndrome de Alagille/metabolismo , Síndrome de Alagille/patologia , Ductos Biliares Intra-Hepáticos/metabolismo , Ductos Biliares Intra-Hepáticos/patologia , Proteínas de Ligação ao Cálcio/genética , Colestase/genética , Colestase/metabolismo , Inativação Gênica , Glucosiltransferases/genética , Glucosiltransferases/metabolismo , Glicosiltransferases/genética , Glicosiltransferases/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/genética , Proteína Jagged-1/genética , Proteína Jagged-1/metabolismo , Fígado/metabolismo , Fígado/patologia , Proteínas de Membrana/genética , Oligonucleotídeos Antissenso/genética , Oligonucleotídeos Antissenso/metabolismo , Fenótipo , Proteínas Serrate-Jagged/genética , Proteínas Serrate-Jagged/metabolismo
16.
Plants (Basel) ; 12(8)2023 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-37111831

RESUMO

In recent decades, the quality of agricultural soils has been seriously affected by the excessive application of pesticides, with herbicides being one of the most abundant. Continuous use of herbicides alters the soil microbial community and beneficial interactions between plants and bacteria such as legume-rhizobia spp. symbiosis, causing a decrease in the biological nitrogen fixation, which is essential for soil fertility. Therefore, the aim of this work was to study the effect of two commonly used herbicides (pendimethalin and clethodim) on the legume-rhizobia spp. symbiosis to improve the effectiveness of this process. Phaseolus vulgaris plants grown in pots with a mixture of soil:perlite (3:1 v/v), showed a 44% inhibition of nitrogen fixation rate with pendimethalin. However, clethodim, specifically used against monocots, did not induce significant differences. Additionally, we analyzed the effect of herbicides on root exudate composition, detecting alterations that might be interfering with the symbiosis establishment. In order to assess the effect of the herbicides at the early nodulation steps, nodulation kinetics in Medicago sativa plants inoculated with Sinorhizobium meliloti were performed. Clethodim caused a 30% reduction in nodulation while pendimethalin totally inhibited nodulation, producing a reduction in bacterial growth and motility as well. In conclusion, pendimethalin and clethodim application reduced the capacity of Phaseolus vulgaris and Medicago sativa to fix nitrogen by inhibiting root growth and modifying root exudate composition as well as bacterial fitness. Thus, a reduction in the use of these herbicides in these crops should be addressed to favor a state of natural fertilization of the soil through greater efficiency of leguminous crops.

17.
Toxics ; 11(4)2023 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-37112525

RESUMO

The present work evaluated the influence of eight different soil remediation techniques, based on the use of residual materials (gypsum, marble, vermicompost) on the reduction in metal(loid)s toxicity (Cu, Zn, As, Pb and Cd) in a polluted natural area. Selected remediation treatments were applied in a field exposed to real conditions and they were evaluated one year after the application. More specifically, five ecotoxicological tests were carried out using different organisms on either the solid or the aqueous (leachate) fraction of the amended soils. Likewise, the main soil properties and the total, water-soluble and bioavailable metal fractions were determined to evaluate their influence on soil toxicity. According to the toxicity bioassays performed, the response of organisms to the treatments differed depending on whether the solid or the aqueous fraction was used. Our results highlighted that the use of a single bioassay may not be sufficient as an indicator of toxicity pathways to select soil remediation methods, so that the joint determination of metal availability and ecotoxicological response will be determinant for the correct establishment of any remediation technique carried out under natural conditions. Our results indicated that, of the different treatments used, the best technique for the remediation of metal(loid)s toxicity was the addition of marble sludge with vermicompost.

18.
Int J Gynecol Pathol ; 42(2): 147-150, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35551153

RESUMO

COL1A1-PDGFB gene fusion uterine sarcoma is a recently described entity which shows some overlapping features with dermatofibrosarcoma protuberans. To date, only 4 cases have been reported in the literature. Due to its rarity, succinct clinicopathologic characteristics are yet to be established. We report a fifth case initially mistaken as a uterine fibroid which histologically proved to be a CD34 + high-grade spindle cell proliferation which on fluorescence in situ hybridization analysis displayed COL1A1-PDGFB gene rearrangement. With this case description we hope to raise awareness and aid in the characterization of this emerging entity.


Assuntos
Dermatofibrossarcoma , Neoplasias Cutâneas , Neoplasias de Tecidos Moles , Humanos , Dermatofibrossarcoma/genética , Hibridização in Situ Fluorescente , Proteínas de Fusão Oncogênica/genética , Proteínas Proto-Oncogênicas c-sis/genética , Neoplasias Cutâneas/patologia
19.
G3 (Bethesda) ; 13(3)2023 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-36504387

RESUMO

The controversial theory of adaptive amplification states gene amplification mutations are induced by selective environments where they are enriched due to the stress caused by growth restriction on unadapted cells. We tested this theory with three independent assays using an Acinetobacter baylyi model system that exclusively selects for cat gene amplification mutants. Our results demonstrate all cat gene amplification mutant colonies arise through a multistep process. While the late steps occur during selection exposure, these mutants derive from low-level amplification mutant cells that form before growth-inhibiting selection is imposed. During selection, these partial mutants undergo multiple secondary steps generating higher amplification over several days to multiple weeks to eventually form visible high-copy amplification colonies. Based on these findings, amplification in this Acinetobacter system can be explained by a natural selection process that does not require a stress response. These findings have fundamental implications to understanding the role of growth-limiting selective environments on cancer development. We suggest duplication mutations encompassing growth factor genes may serve as new genomic biomarkers to facilitate early cancer detection and treatment, before high-copy amplification is attained.


Assuntos
Acinetobacter , Neoplasias , Humanos , Amplificação de Genes , Mutação , Acinetobacter/genética , Neoplasias/genética
20.
Artigo em Inglês | MEDLINE | ID: mdl-38469035

RESUMO

Background: How diabetes mellitus (DM), race/ethnicity, and sex impact ischemic events following coronary artery stent procedures is unknown. Methods: Using the PLATINUM Diversity and PROMUS Element Plus Post-Approval Pooled Study (N = 4184), we examined the impact of race/ethnicity, sex, and DM on coronary stent outcomes. Primary outcome was 1-year major adverse cardiac events (MACE) (MACE composite: death, myocardial infarction [MI], and target vessel revascularization). Results: The study sample included 1437 diabetic patients (501 White men, 470 White women, 246 minority men, 220 minority women) and 2641 patients without medically treated DM (561 minority, 1090 women). Mean age (years) ranged from 61 in minority men to 65 in White women. Diabetic patients had a higher prevalence of atherosclerotic risk factors and comorbidities. Diabetic minority women (DMW; 70% Black, 27% Hispanic) had similar atherosclerotic risk factors to other diabetics, but experienced higher 1-year MACE (14.4% vs 7.5%, P <.01) and MI (4.3% vs 1.6%, P <.01) rates compared with patients without medically treated DM. No other diabetic cohort (White men, White women, minority men) showed an increased risk of MACE vs patients without medically treated DM. The incremental risk of MACE in DMW was associated with insulin use and persisted after risk adjustment (adjusted odds ratio 1.6 vs patients without medically treated DM; 95% CI, 1.0-2.5). Independent predictors of 1-year MACE included insulin use, hyperlipidemia, renal disease, and prior MI. Conclusions: DMW face the highest risk of ischemic events following coronary stenting, driven, in part, by insulin use. Aggressive secondary prevention and strict glycemic control are imperative in this cohort, and further research is warranted to elucidate the biologic mechanisms underpinning these observations. Clinical Trial Registration: NCT02240810 (http://clinicaltrials.gov/).

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