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1.
Heliyon ; 10(13): e33866, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39071556

RESUMEN

A study was conducted in fish processing facilities to investigate the microbial composition, microbial metabolic potential, and distribution of antibiotic resistance genes. Whole metagenomic sequencing was used to analyze microbial communities from different processing rooms, operators and fish products. Taxonomic analyses identified the genera Pseudomonas and Psychrobacter as the most prevalent bacteria. A Principal Component Analysis revealed a distinct separation between fish product and environmental samples, as well as differences between fish product samples from companies processing either Gadidae or Salmonidae fish. Some particular bacterial genera and species were associated with specific processing rooms and operators. Metabolic analysis of metagenome assembled genomes demonstrated variations in microbiota metabolic profiles of microbiota across rooms and fish products. The study also examined the presence of antibiotic-resistance genes in fish processing environments, contributing to the understanding of microbial dynamics, metabolic potential, and implications for fish spoilage.

2.
Biomedicines ; 12(7)2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-39061980

RESUMEN

Around 30-60% of patients with rheumatoid arthritis (RA) present treatment failure to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Chitinase-like proteins (CLPs) (YKL-40, YKL-39, SI-CLP) might play a role, as they are associated with the inflammatory process. This study aimed to evaluate CLP utility as a biomarker in the treatment failure of csDMARDs. A case-control study included 175 RA patients classified into two groups based on therapeutic response according to DAS28-ESR: responders (DAS28 < 3.2); non-responders (DAS28 ≥ 3.2). CLP serum levels were determined by ELISA. Multivariable logistic regression and receiver operating characteristic (ROC) curves were used to evaluate CLPs' utility as biomarkers of treatment failure. Non-responders presented higher levels of YKL-40, YKL-39, and SI-CLP compared with responders (all: p < 0.001). YKL-40 correlated positively with YKL-39 (rho = 0.39, p < 0.001) and SI-CLP (rho = 0.23, p = 0.011) and YKL-39 with SI-CLP (rho = 0.34, p < 0.001). The addition of CLPs to the regression models improves diagnostic accuracy (AUC 0.918) compared to models including only clinical classical variables (AUC 0.806) p < 0.001. Non-responders were positive for all CLPs in 35.86%. Conclusions: CLPs could be considered as a useful biomarker to assess treatment failure, due to their association with clinical variables and improvement to the performance of regression models.

4.
Int J Cardiol ; 413: 132340, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38992809

RESUMEN

BACKGROUND: The current incidence and outcomes of structural transcatheter procedures in heart transplant (HTx) recipients and left-ventricular assist devices (LVAD) carriers is unknown. AIMS: To provide insights on structural transcatheter procedures performed across HTx and LVAD patients in Spain. METHODS: Multicenter, ambispective, observational nationwide registry. RESULTS: Until May/2023, 36 percutaneous structural interventions were performed (78% for HTx and 22% for LVAD) widely varying among centers (0%-1.4% and 0%-25%, respectively). Percutaneous mitral transcatheter edge-to-edge (TEER) was the most common (n = 12, 33.3%), followed by trancatheter aortic valve replacement (n = 11, 30.5%), and tricuspid procedures (n = 9, 25%). Mitral TEER resulted in mild residual mitral regurgitation in all but one case, mean gradient was <5 mmHg in 75% of them at 1-year, with no mortality and 8.3% re-admission rate. Tricuspid TEER resulted in 100% none/mild residual regurgitation with a 1-year mortality and readmission rates of 22% and 28.5%, respectively. Finally, trancatheter aortic valve replacement procedures (n = 8 in LVADs due to aortic regurgitation and n = 3 in HTx), were successful in all cases with one prosthesis degeneration leading to severe aortic regurgitation at 1-year, 18.2% mortality rate and no re-admissions. Globally, major bleeding rates were 7.9% and 12.5%, thromboembolic events 3.7% and 12.5%, readmissions 37% and 25%, and mortality 22% and 25%, in HTx and LVADs respectively. No death was related to the implanted transcatheter device. CONCLUSIONS: Most centers with HTx/LVAD programs perform structural percutaneous procedures but with very inconsistent incidence. They were associated with good safety and efficacy, but larger studies are required to provide formal recommendations.

5.
Sci Rep ; 14(1): 15500, 2024 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-38969684

RESUMEN

The incidence of Pseudomonas aeruginosa infections in healthcare environments, particularly in low-and middle-income countries, is on the rise. The purpose of this study was to provide comprehensive genomic insights into thirteen P. aeruginosa isolates obtained from Egyptian healthcare settings. Phenotypic analysis of the antimicrobial resistance profile and biofilm formation were performed using minimum inhibitory concentration and microtiter plate assay, respectively. Whole genome sequencing was employed to identify sequence typing, resistome, virulome, and mobile genetic elements. Our findings indicate that 92.3% of the isolates were classified as extensively drug-resistant, with 53.85% of these demonstrating strong biofilm production capabilities. The predominant clone observed in the study was ST773, followed by ST235, both of which were associated with the O11 serotype. Core genome multi-locus sequence typing comparison of these clones with global isolates suggested their potential global expansion and adaptation. A significant portion of the isolates harbored Col plasmids and various MGEs, all of which were linked to antimicrobial resistance genes. Single nucleotide polymorphisms in different genes were associated with the development of antimicrobial resistance in these isolates. In conclusion, this pilot study underscores the prevalence of extensively drug-resistant P. aeruginosa isolates and emphasizes the role of horizontal gene transfer facilitated by a diverse array of mobile genetic elements within various clones. Furthermore, specific insertion sequences and mutations were found to be associated with antibiotic resistance.


Asunto(s)
Antibacterianos , Pruebas de Sensibilidad Microbiana , Pseudomonas aeruginosa , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/aislamiento & purificación , Egipto/epidemiología , Humanos , Antibacterianos/farmacología , Infecciones por Pseudomonas/microbiología , Infecciones por Pseudomonas/epidemiología , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Secuenciación Completa del Genoma/métodos , Genómica/métodos , Genoma Bacteriano , Evolución Molecular , Farmacorresistencia Bacteriana/genética , Tipificación de Secuencias Multilocus , Polimorfismo de Nucleótido Simple , Farmacorresistencia Bacteriana Múltiple/genética , Filogenia
6.
Microb Biotechnol ; 17(7): e14530, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39017204

RESUMEN

Antimicrobial resistance (AMR) represents a significant global health problem which challenges Sustainable Development Goal 3 of the United Nations, with growing concerns about the possibility of AMR transmission through the food chain. The indiscriminate use of antimicrobials for the treatment of food production animals and for agricultural crop improvement, in addition to the direct discharge of livestock farm residues to sewage and the use of animal manure in agriculture, are among the factors that can facilitate the selection and transmission of AMR throughout the food chain. The study of food microbiomes has been boosted by the advent of next-generation sequencing techniques, which have enabled gaining in-depth understanding of the diversity of antimicrobial resistance genes present in food and associated environments (the so-called resistome). The aim of this review is to provide an accurate and comprehensive overview of the knowledge currently available on the resistome of the most frequently consumed foods worldwide, from a One Health perspective. To this end, the different metagenomic studies which have been conducted to characterize the resistome of foods are compiled and critically discussed.


Asunto(s)
Salud Única , Animales , Humanos , Farmacorresistencia Bacteriana/genética , Cadena Alimentaria , Antibacterianos/farmacología , Metagenómica , Microbiología de Alimentos , Bacterias/genética , Bacterias/efectos de los fármacos , Bacterias/clasificación , Bacterias/aislamiento & purificación
8.
PeerJ Comput Sci ; 10: e1992, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38855234

RESUMEN

Mental health issues are a global concern, with a particular focus on the rise of depression. Depression affects millions of people worldwide and is a leading cause of suicide, particularly among young people. Recent surveys indicate an increase in cases of depression during the COVID-19 pandemic, which affected approximately 5.4% of the population in Spain in 2020. Social media platforms such as X (formerly Twitter) have become important hubs for health information as more people turn to these platforms to share their struggles and seek emotional support. Researchers have discovered a link between emotions and mental illnesses such as depression. This correlation provides a valuable opportunity for automated analysis of social media data to detect changes in mental health status that might otherwise go unnoticed, thus preventing more serious health consequences. Therefore, this research explores the field of emotion analysis in Spanish towards mental disorders. There are two contributions in this area. On the one hand, the compilation, translation, evaluation and correction of a novel dataset composed of a mixture of other existing datasets in the bibliography. This dataset compares a total of 16 emotions, with an emphasis on negative emotions. On the other hand, the in-depth evaluation of this novel dataset with several state-of-the-art transformers based on encoder-only and encoder-decoder architectures. The analysis compromises monolingual, multilingual and distilled models as well as feature integration techniques. The best results are obtained with the encoder-only MarIA model, with a macro-average F1 score of 60.4771%.

9.
Behav Sci (Basel) ; 14(6)2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38920763

RESUMEN

Associations and families demand the need to raise awareness of the implications in the cognitive and behavioral development of children with Fetal Alcohol Spectrum Disorder (FASD) that affect their learning and school participation. This study aims to generate a profile of executive and behavioral functioning in children and adolescents diagnosed with FASD. A probabilistic sampling by clusters (associations for individuals with FASD) is applied. The sample is composed of 66 families from three associations. The BRIEF-2 and SENA tests were administered to assess executive and behavioral functioning domains. Data analysis found that the executive and behavioral functioning profile of individuals with FASD varies with age, with greater impairment in middle and late adolescence. Likewise, the domain of executive functioning most affected in any of the developmental stages is working memory. Finally, cognitive impairment in the executive functioning domains has a direct impact on the social and adaptive functioning of people with FASD.

10.
Antibiotics (Basel) ; 13(6)2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38927204

RESUMEN

Rifampicin is one of the mainstays in treating staphylococcal prosthetic joint infection (PJI). However, discontinuation due to intolerance, drug interactions, and adverse events is common. Two-stage revision surgery remains the gold standard, with the number of revision arthroplasties steadily increasing. This study aims to evaluate the effectiveness and safety of a novel two-stage revision protocol for staphylococcal prosthetic joint infection (PJI) utilizing bone cement spacers loaded with multiple high doses of antibiotics. Additionally, it seeks to analyze outcomes in patients ineligible for rifampicin treatment. A retrospective review of 43 cases of staphylococcal hip and knee prosthetic joint infections (PJIs) from 2012 to 2020 was conducted. In all instances, a commercial cement containing 1 g of gentamicin and 1 g of clindamycin, augmented with 4 g of vancomycin and 2 g of ceftazidime, was employed to cast a spacer manually after thorough surgical debridement. We report an eradication rate of 82%, with no significant differences observed (p = 0.673) between patients treated with (84%, n = 19) and without rifampicin (79%, n = 24). There were no disparities in positive culture rates (7%), spacer replacement (18%), or survival analysis (p = 0.514) after an average follow-up of 68 months (range 10-147) in the absence of systemic toxicity and surgical complications superimposable to those previously reported. In conclusion, two-stage revision with local high doses of ceftazidime, vancomycin, gentamicin, and clindamycin demonstrates high effectiveness in treating staphylococcal PJIs. Notably, systemic rifampicin does not influence the outcomes. This protocol, with multiple high doses of antibiotics loaded into the bone cement spacer, is presented as a viable and safe alternative for patients unsuitable for rifampicin treatment.

11.
Cureus ; 16(5): e60378, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38883025

RESUMEN

Hemorrhagic cholecystitis is an uncommon presentation of acute cholecystitis. Due to its etiology and unspecific clinical data, it is an entity that represents a diagnostic challenge. We present a case of a 70-year-old male with diabetes type 2, hypertension, and chronic kidney disease with hemodialysis, who attended the emergency department with sudden-onset abdominal pain in the epigastrium. The patient presented no additional symptoms, a normal electrocardiogram, but due to the characteristics of the pain and elevated troponin I, emergency medicine specialists considered an acute coronary syndrome and initiated antiplatelet and anticoagulant therapy. Due to persistent abdominal pain, a decrease in hemoglobin, and the onset of arterial hypotension, a computed tomography (CT) scan was performed, which revealed perforation of the gallbladder, apparent hemorrhagic cholecystitis, and hemoperitoneum. The patient underwent emergent surgery, where CT findings were confirmed. In our case, the suspicion of hemorrhagic cholecystitis arose until the clinical case was advanced, after receiving anticoagulant and antiplatelet therapy, and it was confirmed during surgery and with histopathology. This concludes that hemorrhagic cholecystitis is a rare disease and difficult to diagnose. Therefore, studies should focus on clinical presentation and risk factors (e.g., trauma, malignancy, renal failure, cirrhosis, and anticoagulation therapy) to promote early diagnosis and avoid complications.

12.
J Subst Use Addict Treat ; 164: 209440, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38880303

RESUMEN

INTRODUCTION: Substance use disorders (SUD) are associated with HIV acquisition and care disruptions. Most research focuses on clinical samples; however, we used a nationally representative, community-based sample to estimate SUD treatment need and utilization by HIV status. METHODS: We included participants from the 2015-2019 National Survey on Drug Use and Health aged 18 and older who met past-year DSM-IV SUD criteria (n = 22,166). Participants self-reported whether a healthcare professional ever told them they had HIV or AIDS [i.e., people with HIV (PWH), non-PWH, HIV status unknown]. Outcomes included past-year: 1) any SUD treatment use; 2) any specialty SUD treatment use; and 3) perceived SUD treatment need. Survey weighted multivariable logistic regression models estimated the likelihood of each outcome by HIV status, adjusting for age, sex, race/ethnicity, education, survey year, health insurance status, and household income. RESULTS: Overall, 0.5 % were PWH and 0.8 % had an HIV unknown status. Any past-year SUD treatment utilization was low across all groups (10.3 % non-PWH, 24.2 % PWH, and 17.3 % HIV status unknown respondents). Specialty SUD treatment utilization was reported by 7.2 % of non-PWH, 17.8 % PWH, and 10.9 % HIV status unknown respondents. Perceived treatment need was reported by 4.9 % of non-PWH, 12.4 % of PWH, and 3.7 % of HIV status unknown respondents. In adjusted models, PWH were more likely than non-PWH to report any past-year SUD treatment utilization (aOR = 2.06; 95 % CI = 1.08-3.94) or past-year specialty SUD treatment utilization (aOR = 2.07; 95 % CI = 1.07-4.01). Among those with a drug use disorder other than cannabis, respondents with HIV-unknown status were less likely than HIV-negative individuals to report past-year perceived treatment need (aOR = 0.39; 95 % CI = 0.20-0.77). CONCLUSIONS: Despite high SUD treatment need among PWH, more than three quarters of PWH with SUD reported no past-year treatment. Compared to non-PWH, PWH had higher treatment utilization and higher specialty treatment utilization, but SUD treatment was low across all groups. As SUD is associated with adverse HIV outcomes, our findings highlight the need for the integration of SUD treatment with HIV testing and care. Increasing access to SUD treatment could help reduce negative SUD-related outcomes along the HIV care continuum.

13.
J Int Soc Prev Community Dent ; 14(2): 89-97, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38827351

RESUMEN

Aim: Cone beam computed tomography has become an attractive method for implant planning. However, in most cases, not all the information is taken advantage of and often the radiographic evaluation of bone quality is based on subjective assessment by the individual clinician. Therefore, the aim of this study was to examine classifications of bone tissue characteristics and methods for assessing them in dental implant planning and placement studies. Materials and Methods: Three databases (Pubmed, Scopus, Web of Science) were searched using specific index terms: "Bone quality, bone quantity, bone density, cone-beam CT and cone-beam computed tomography". Three reviewers selected titles and analyzed abstracts according to inclusion and exclusion criteria. Some descriptions of bone tissue characteristics (bone quality, density, and quantity) used before or during dental implant placement were selected and categorized. Results: The search yielded 442 titles. A total of 32 articles were selected and read in full text. Seventeen articles were considered relevant. Different classification systems were found to evaluate bone tissue characteristics as well as different examination protocols. Thirteen publications included in this review reported on bone quality and quantity using the Lekholm and Zarb classification. However, only four studies implemented and/or proposed modifications of the Lekholm and Zarb system. Four other publications described bone quality according to different classification systems such as Misch, University of California Los Angeles (UCLA), or Trisi and Rao. The assessment methods were often briefly described (or not described at all in one publication). Of the articles analyzed, five presented observer performance, whereas three presented diagnostic accuracy of the assessment method. Conclusion: Currently, there are different classification systems applied to dental implant planning and placement, particularly regarding whether bone quality or quantity affects treatment outcomes. However, most authors have not validated the diagnostic accuracy and reproducibility of the classification used. Therefore, it is necessary to develop a classification system consistent with characteristics of bone tissue, taking into consideration an adequate description of bone tissue assessment methods, their diagnostic accuracy, and observer performance.

14.
AIDS Behav ; 28(8): 2650-2654, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38833065

RESUMEN

Inequities in eHealth research enrollment persist among Black and Latinx sexual minoritized men (SMM) partly due to socio-ecological barriers. Less is known about how personality traits are associated with their study enrollment. We examined the role of personality traits among 1,285 U.S. Black and Latinx SMM living with HIV recruited from sexual networking websites/apps for an eHealth intervention. Lower neuroticism and higher openness were associated with greater odds of study enrollment among Latinx SMM. Given these exploratory findings, future research should examine this phenomenon, along with well-established socio-ecological factors such as medical mistrust to better understand eHealth study enrollment gaps among Black and Latinx SMM.


Asunto(s)
Negro o Afroamericano , Infecciones por VIH , Hispánicos o Latinos , Personalidad , Telemedicina , Humanos , Masculino , Infecciones por VIH/psicología , Infecciones por VIH/etnología , Infecciones por VIH/epidemiología , Adulto , Negro o Afroamericano/psicología , Negro o Afroamericano/estadística & datos numéricos , Hispánicos o Latinos/psicología , Hispánicos o Latinos/estadística & datos numéricos , Persona de Mediana Edad , Estados Unidos/epidemiología , Minorías Sexuales y de Género/psicología , Minorías Sexuales y de Género/estadística & datos numéricos , Conducta Sexual/psicología , Adulto Joven , Homosexualidad Masculina/psicología , Homosexualidad Masculina/estadística & datos numéricos , Homosexualidad Masculina/etnología
16.
Int Angiol ; 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38864688

RESUMEN

INTRODUCTION: The pathogenesis of deep vein thrombosis (DVT) has been explained by an interplay between a changed blood composition, vein wall alteration, and blood flow abnormalities. A comprehensive investigation of these components of DVT pathogenesis has substantially promoted our understanding of thrombogenesis in the venous system. Meanwhile, the process of DVT initiation remains obscure. This systematic review aims to collect, analyze, and synthesize the published evidence to propose hypoxia as a possible trigger of DVT. EVIDENCE ACQUISITION: An exhaustive literature search was conducted across multiple electronic databased including PubMed, EMBASE, Scopus, and Web of Science to identify studies pertinent to the research hypothesis. The search was aimed at exploring the connection between hypoxia, reoxygenation, and the initiation of deep vein thrombosis (DVT). The following key words were used: "deep vein thrombosis," "venous thrombosis," "venous thromboembolism," "hypoxia," "reoxygenation," "venous valve," and "venous endothelium." Reviews, case reports, editorials, and letters were excluded. EVIDENCE SYNTHESIS: Based on the systematic search outcome, 156 original papers relevant to the issue were selected for detailed review. These studies encompassed a range of experimental and observational clinical research, focusing on various aspects of DVT, including the anatomical, physiological, and cellular bases of the disease. A number of studies suggested limitations in the traditional understanding of Virchow's triad as an acceptable explanation for DVT initiation. Emerging evidence points to more complex interactions and additional factors that may be critical in the early stages of thrombogenesis. The role of venous valves has been recognized but remains underappreciated, with several studies indicating that these sites may act as primary loci for thrombus formation. A collection of studies describes the effects of hypoxia on venous endothelial cells at the cellular and molecular levels. Hypoxia influences several pathways that regulate endothelial cell permeability, inflammatory response, and procoagulation activity, underpinning the endothelial dysfunction noted in DVT. CONCLUSIONS: Hypoxia of the venous valve may serve as an independent hypothesis to outline the DVT triggering process. Further research projects in this field may discover new molecular pathways responsible for the disease and suggest new therapeutic targets.

17.
Gigascience ; 132024 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-38940768

RESUMEN

BACKGROUND: Colletotrichum fungi infect a wide diversity of monocot and dicot hosts, causing diseases on almost all economically important plants worldwide. Colletotrichum is also a suitable model for studying gene family evolution on a fine scale to uncover events in the genome associated with biological changes. RESULTS: Here we present the genome sequences of 30 Colletotrichum species covering the diversity within the genus. Evolutionary analyses revealed that the Colletotrichum ancestor diverged in the late Cretaceous in parallel with the diversification of flowering plants. We provide evidence of independent host jumps from dicots to monocots during the evolution of Colletotrichum, coinciding with a progressive shrinking of the plant cell wall degradative arsenal and expansions in lineage-specific gene families. Comparative transcriptomics of 4 species adapted to different hosts revealed similarity in gene content but high diversity in the modulation of their transcription profiles on different plant substrates. Combining genomics and transcriptomics, we identified a set of core genes such as specific transcription factors, putatively involved in plant cell wall degradation. CONCLUSIONS: These results indicate that the ancestral Colletotrichum were associated with dicot plants and certain branches progressively adapted to different monocot hosts, reshaping the gene content and its regulation.


Asunto(s)
Colletotrichum , Evolución Molecular , Genoma Fúngico , Transcriptoma , Colletotrichum/genética , Colletotrichum/patogenicidad , Filogenia , Adaptación Fisiológica/genética , Perfilación de la Expresión Génica/métodos , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/genética
18.
Neuromuscul Disord ; 41: 8-19, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38865917

RESUMEN

We investigated the comorbidities, associated factors, and the relationship between anthropometric measures and respiratory function and functional abilities in adults with Duchenne muscular dystrophy (DMD). This was a single-centre cross-sectional study in genetically diagnosed adults with DMD (>16 years old). Univariate and multivariate analyses identified factors associated with dysphagia, constipation, Body Mass Index (BMI), and weight. Regression analysis explored associations between BMI, weight, and respiratory/motor abilities. We included 112 individuals (23.4 ± 5.2 years old), glucocorticoid-treated 66.1 %. The comorbidities frequency was 61.6 % scoliosis (61.0 % of them had spinal surgery), 36.6 % dysphagia, 36.6 % constipation, and 27.8 % urinary conditions. The use of glucocorticoids delayed the time to spinal surgery. The univariate analysis revealed associations between dysphagia and constipation with age, lack of glucocorticoid treatment, and lower respiratory and motor function. In the multivariate analysis, impaired cough ability remained as the factor consistently linked to both conditions. Constipation associated with lower BMI and weight. BMI and weight positively correlated with respiratory parameters, but they did not associate with functional abilities. Glucocorticoids reduce the frequency of comorbidities in adults with DMD. The ability to cough can help identifying dysphagia and constipation. Lower BMI and weight in individuals with DMD with compromised respiratory function may suggest a higher calories requirement.


Asunto(s)
Índice de Masa Corporal , Comorbilidad , Estreñimiento , Trastornos de Deglución , Glucocorticoides , Distrofia Muscular de Duchenne , Humanos , Distrofia Muscular de Duchenne/complicaciones , Distrofia Muscular de Duchenne/tratamiento farmacológico , Distrofia Muscular de Duchenne/fisiopatología , Distrofia Muscular de Duchenne/epidemiología , Masculino , Estudios Transversales , Adulto , Adulto Joven , Glucocorticoides/uso terapéutico , Adolescente , Trastornos de Deglución/epidemiología , Trastornos de Deglución/etiología , Trastornos de Deglución/fisiopatología , Estreñimiento/epidemiología , Femenino , Antropometría , Peso Corporal
19.
J Med Chem ; 67(11): 9150-9164, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38753759

RESUMEN

The synthesis and pharmacological activity of a new series of thieno[2,3-d]pyrimidin-4(3H)-one derivatives as sigma-1 receptor (σ1R) ligands are reported. A hit from a high-throughput screening program was evolved into a highly potent and selective σ1R agonist (14qR) that contains a free NH group as positive ionizable moiety, not fulfilling the usual pharmacophoric features of the σ1R. The compound shows good physicochemical and ADMET characteristics, displays an agonist profile in the binding immunoglobulin protein/σ1R association assay, induces neuron viability in an in vitro model of ß-amyloid peptide intoxication, and presents positive results against recognition memory impairment induced by hippocampal injection of Aß peptide in rats after oral treatment, altogether making 14qR (WLB-87848) an interesting candidate for neuroprotection.


Asunto(s)
Fármacos Neuroprotectores , Receptores sigma , Receptor Sigma-1 , Animales , Receptores sigma/agonistas , Receptores sigma/metabolismo , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/síntesis química , Fármacos Neuroprotectores/química , Ratas , Humanos , Masculino , Relación Estructura-Actividad , Péptidos beta-Amiloides/metabolismo , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Pirimidinas/farmacología , Pirimidinas/síntesis química , Pirimidinas/química , Trastornos de la Memoria/tratamiento farmacológico , Supervivencia Celular/efectos de los fármacos , Pirimidinonas/farmacología , Pirimidinonas/síntesis química , Pirimidinonas/química , Ratas Wistar , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo
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