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1.
Meat Sci ; 216: 109558, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38850887

RESUMO

Pale, Soft, and Exudative (PSE)-like pork defects are associated with fiber destruction and pale discoloration and have become a severe economic burden for the European meat sector. However, robust detection of PSE-like pork and its diverse features is challenging and makes studies into defect causation difficult. Implementation of histological examination may improve our knowledge about less-known features linked to PSE-like defects. Here we evaluate if a new histological protocol can reveal how myopathy in ham may be associated with visual and traditional physicochemical anomalies of PSE-like pork. We first created a list of pathological features, quantified them, and integrated them into a myodegeneration scoring scheme (MYO) for semimembranosus muscle sections. We then explored potential associations between overall MYO scoring and individual histology features with visual PSE-like defect scoring (DES) and with individual meat quality variables [pHu, color: L*, a*, b* (CIELAB), bioimpedance, and near-infrared spectroscopy (NIR)]. As the primary finding of this study, we show a significant association between overall myopathy (MYO) scoring and PSE-like defect (DES) scores. We also found associations of specific myopathy features with DES scores, and of overall MYO scoring with specific quality variables. In all, our data suggest links between signs of acute myodegeneration and PSE-like defects. Our data, hence, supports the implementation of semi-quantitative histopathological approaches for diagnosing PSE-like pork features and may help identify the underlying mechanisms behind these defects.

2.
Aliment Pharmacol Ther ; 59(12): 1604-1615, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38690746

RESUMO

BACKGROUND: Suboptimal response to ursodeoxycholic acid occurs in 40% of primary biliary cholangitis (PBC) patients, affecting survival. Achieving a deep response (normalisation of alkaline phosphatase [ALP] and bilirubin ≤0.6 upper limit of normal) improves survival. Yet, the long-term effectiveness of second-line treatments remains uncertain. AIMS: To evaluate the long-term effectiveness of obeticholic acid (OCA) ± fibrates. Focusing on biochemical response (ALP ≤1.67 times the upper limit of normal, with a decrease of at least 15% from baseline and normal bilirubin levels), normalisation of ALP, deep response and biochemical remission (deep response plus aminotransferase normalisation). METHODS: We conducted a longitudinal, observational, multicentre study involving ursodeoxyccholic acid non-responsive PBC patients (Paris-II criteria) from Spain and Portugal who received OCA ± fibrates. RESULTS: Of 255 patients, median follow-up was 35.1 months (IQR: 20.2-53). The biochemical response in the whole cohort was 47.2%, 61.4% and 68.6% at 12, 24 and 36 months. GLOBE-PBC and 5-year UK-PBC scores improved (p < 0.001). Triple therapy (ursodeoxycholic acid plus OCA plus fibrates) had significantly higher response rates than dual therapy (p = 0.001), including ALP normalisation, deep response and biochemical remission (p < 0.001). In multivariate analysis, triple therapy remained independently associated with biochemical response (p = 0.024), alkaline phosphatase normalisation, deep response and biochemical remission (p < 0.001). Adverse effects occurred in 41.2% of cases, leading to 18.8% discontinuing OCA. Out of 55 patients with cirrhosis, 12 developed decompensation. All with baseline portal hypertension. CONCLUSION: Triple therapy was superior in achieving therapeutic goals in UDCA-nonresponsive PBC. Decompensation was linked to pre-existing portal hypertension.


Assuntos
Fosfatase Alcalina , Ácido Quenodesoxicólico , Colagogos e Coleréticos , Quimioterapia Combinada , Cirrose Hepática Biliar , Ácido Ursodesoxicólico , Humanos , Ácido Quenodesoxicólico/análogos & derivados , Ácido Quenodesoxicólico/uso terapêutico , Masculino , Feminino , Pessoa de Meia-Idade , Ácido Ursodesoxicólico/uso terapêutico , Estudos Longitudinais , Cirrose Hepática Biliar/tratamento farmacológico , Idoso , Resultado do Tratamento , Fosfatase Alcalina/sangue , Colagogos e Coleréticos/uso terapêutico , Ácidos Fíbricos/uso terapêutico , Espanha , Bilirrubina/sangue , Adulto
3.
Rev Clin Esp (Barc) ; 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38701969

RESUMO

INTRODUCTION: The global increase in sexual transmitted infections (STI) makes it necessary to seek public health strategies that facilitate rapid and minimally invasive diagnosis. The objective was to evaluate the concordance between vaginal and endocervical samples for STI diagnosis. MATERIALS AND METHODS: A retrospective cross-sectional study was carried out on vaginal and endocervical samples from women attended in our reference area with symptoms suggestive of vulvovaginitis or for STI screening during the study period. RESULTS: A total of 130 paired samples were analyzed; fifty-seven and 59 samples were positive for vaginal and endocervical specimens (Kappa index of 0.969 (Standard error = 0.022). The sensitivity of the vaginal samples was 96.5% (IC95%: 87.2-99.4), with a specificity of 100% (IC95%: 93.0-100). DISCUSSION: The introduction of STI screening in vaginal samples in our environment can facilitate rapid and effective diagnosis and allow early treatment of STI. Additionally, it facilitates sample collection and diagnosis in the community setting, essential for optimal screening.

4.
Rehabilitacion (Madr) ; 58(3): 100850, 2024 May 04.
Artigo em Espanhol | MEDLINE | ID: mdl-38705100

RESUMO

INTRODUCTION: The presence of different complications whilst follow-up amputee patients reaches 10-80%. The main objective of this research is to assess the impact of these in the return-to-work of lower-limb traumatic amputation cases. MATERIALS AND METHODS: A retrospective cohort research was carried out. Clinic-demographic variables information was recollected in order to assess its linkage to different medical-surgical complications and functional outcomes. Survival curves were created to evaluate the return-to-work of patients with and without complications. RESULTS: A total of 46 patients, on average aged 45.7 years old (91.3% men, 71.7% without comorbidities), were included on this research. The most frequent level of amputation was transtibial (65.2%). Residual limb pain, phantom pain, dermatological-infectious complications and painful neuroma were registered in 80.4%, 58.7%, 50% y 30.4% of the cases respectively. Half of the patients had returned to their workplace after 2years of post-surgical follow-up. The return-to-work rates were significantly lower in patients suffering from residual limb pain (p=0.0083) and from painful neuroma (p=0.0051). CONCLUSION: Complications are frequent during traumatic-amputee patients' follow-up and, some of them, may impact on the return-to-work rate.

5.
Pharmaceuticals (Basel) ; 17(5)2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38794218

RESUMO

Astrocytes play a pivotal role in maintaining brain homeostasis. Recent research has highlighted the significance of palmitic acid (PA) in triggering pro-inflammatory pathways contributing to neurotoxicity. Furthermore, Genomic-scale metabolic models and control theory have revealed that metabolic switches (MSs) are metabolic pathway regulators by potentially exacerbating neurotoxicity, thereby offering promising therapeutic targets. Herein, we characterized these enzymatic MSs in silico as potential therapeutic targets, employing protein-protein and drug-protein interaction networks alongside structural characterization techniques. Our findings indicate that five MSs (P00558, P04406, Q08426, P09110, and O76062) were functionally linked to nervous system drug targets and may be indirectly regulated by specific neurological drugs, some of which exhibit polypharmacological potential (e.g., Trifluperidol, Trifluoperazine, Disulfiram, and Haloperidol). Furthermore, four MSs (P00558, P04406, Q08426, and P09110) feature ligand-binding or allosteric cavities with druggable potential. Our results advocate for a focused exploration of P00558 (phosphoglycerate kinase 1), P04406 (glyceraldehyde-3-phosphate dehydrogenase), Q08426 (peroxisomal bifunctional enzyme, enoyl-CoA hydratase, and 3-hydroxyacyl CoA dehydrogenase), P09110 (peroxisomal 3-ketoacyl-CoA thiolase), and O76062 (Delta(14)-sterol reductase) as promising targets for the development or repurposing of pharmacological compounds, which could have the potential to modulate lipotoxic-altered metabolic pathways, offering new avenues for the treatment of related human diseases such as neurological diseases.

6.
Int J Pharm ; 658: 124222, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38735632

RESUMO

Dry eye disease (DED) is a chronic multifactorial disorder of the ocular surface caused by tear film dysfunction and constitutes one of the most common ocular conditions worldwide. However, its treatment remains unsatisfactory. While artificial tears are commonly used to moisturize the ocular surface, they do not address the underlying causes of DED. Apigenin (APG) is a natural product with anti-inflammatory properties, but its low solubility and bioavailability limit its efficacy. Therefore, a novel formulation of APG loaded into biodegradable and biocompatible nanoparticles (APG-NLC) was developed to overcome the restricted APG stability, improve its therapeutic efficacy, and prolong its retention time on the ocular surface by extending its release. APG-NLC optimization, characterization, biopharmaceutical properties and therapeutic efficacy were evaluated. The optimized APG-NLC exhibited an average particle size below 200 nm, a positive surface charge, and an encapsulation efficiency over 99 %. APG-NLC exhibited sustained release of APG, and stability studies demonstrated that the formulation retained its integrity for over 25 months. In vitro and in vivo ocular tolerance studies indicated that APG-NLC did not cause any irritation, rendering them suitable for ocular topical administration. Furthermore, APG-NLC showed non-toxicity in an epithelial corneal cell line and exhibited fast cell internalization. Therapeutic benefits were demonstrated using an in vivo model of DED, where APG-NLC effectively reversed DED by reducing ocular surface cellular damage and increasing tear volume. Anti-inflammatory assays in vivo also showcased its potential to treat and prevent ocular inflammation, particularly relevant in DED patients. Hence, APG-NLC represent a promising system for the treatment and prevention of DED and its associated inflammation.


Assuntos
Apigenina , Portadores de Fármacos , Síndromes do Olho Seco , Lipídeos , Nanopartículas , Animais , Apigenina/administração & dosagem , Apigenina/química , Apigenina/farmacologia , Apigenina/farmacocinética , Portadores de Fármacos/química , Síndromes do Olho Seco/tratamento farmacológico , Humanos , Coelhos , Lipídeos/química , Lipídeos/administração & dosagem , Linhagem Celular , Nanopartículas/química , Administração Oftálmica , Liberação Controlada de Fármacos , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/farmacocinética , Tamanho da Partícula , Nanoestruturas/administração & dosagem , Nanoestruturas/química , Masculino
7.
Curr Urol Rep ; 25(6): 117-124, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38763948

RESUMO

PURPOSE OF REVIEW: Renal cell carcinoma presents a unique proclivity for vascular involvement giving rise to a peculiar form of locally advanced disease so-called tumor thrombus. To date, the only curative strategy for these cases remains surgery, which should aim to remove every vestige of macroscopic disease. Most of the preexisting literature advocates opening the vena cava to allow tumor thrombus removal and subsequent venous suture closure. However, inferior vena cava circumferential resection (cavectomy) without caval replacement is possible in the majority of cases since progressive occlusion facilitates the development of a collateral venous network aimed at maintaining cardiac preload. RECENT FINDINGS: Radical nephrectomy with tumor thrombectomy remains a surgical challenge not exempt of operative complications even in experienced hands. In opposition to what traditional cavotomy and thrombus withdrawal can offer, circumferential cavectomy without caval replacement would provide comparable or even better oncologic control, decrease the likelihood of operative bleeding, and prevent the development of perioperative pulmonary embolism. This review focuses on the rationale of circumferential IVC resection without caval replacement and the important technical aspects of this approach in cases of renal cell carcinoma with vascular involvement. We also include an initial report on the surgical outcomes of a contemporary series of patients managed under this approach at our center.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Células Neoplásicas Circulantes , Nefrectomia , Veia Cava Inferior , Humanos , Carcinoma de Células Renais/cirurgia , Neoplasias Renais/cirurgia , Veia Cava Inferior/cirurgia , Nefrectomia/métodos , Trombectomia/métodos
8.
Nat Plants ; 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38806655

RESUMO

The endosperm is a reproductive tissue supporting embryo development. In most flowering plants, the initial divisions of endosperm nuclei are not succeeded by cellularization; this process occurs only after a specific number of mitotic cycles have taken place. The timing of cellularization significantly influences seed viability and size. Previous research implicated auxin as a key factor in initiating nuclear divisions and determining the timing of cellularization. Here we uncover the involvement of a family of clustered auxin response factors (cARFs) as dosage-sensitive regulators of endosperm cellularization. cARFs, maternally expressed and paternally silenced, are shown to induce cellularization, thereby restricting seed growth. Our findings align with the predictions of the parental conflict theory, suggesting that cARFs represent major molecular targets in this conflict. We further demonstrate a recurring amplification of cARFs in the Brassicaceae, suggesting an evolutionary response to parental conflict by reinforcing maternal control over endosperm cellularization. Our study highlights that antagonistic parental control on endosperm cellularization converges on auxin biosynthesis and signalling.

9.
Acta Ortop Mex ; 38(2): 119-122, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38782479

RESUMO

INTRODUCTION: metacarpophalangeal dislocations of the thumb are not very frequent injuries, it is necessary to know the anatomy of the region to know possible causes of interposition that prevent a closed reduction of this pathology. CASE PRESENTATION: we present the case of a 75-year-old woman with a post-traumatic metacarpophalangeal dislocation of the thumb that required open reduction and surgical repair. In this procedure, we performed reduction of the dislocation, mobilization of the interposed structures, repair of the capsule and reinsertion of the ulnar collateral ligament. The early mobilization protocol helped to obtain very good results. CONCLUSION: it is imperative to consider possible associated injuries during the acute phase to achieve optimal short, medium, and long-term outcomes for our patients. A comprehensive and proactive approach to diagnosis and treatment is vital in effectively addressing this pathology and minimizing its potential sequelae.


INTRODUCCIÓN: las luxaciones metacarpofalángicas del pulgar no son lesiones muy frecuentes, es necesario conocer la anatomía de la región para conocer posibles causas de interposición que impidan una reducción cerrada de esta patología. PRESENTACIÓN DEL CASO: presentamos el caso de una mujer de 75 años con luxación metacarpofalángica postraumática del pulgar que requirió reducción abierta y reparación quirúrgica. En este procedimiento realizamos reducción de la luxación, movilización de las estructuras interpuestas, reparación de la cápsula y reinserción del ligamento colateral cubital. El protocolo de movilización temprana ayudó a obtener muy buenos resultados. CONCLUSIÓN: es imperativo considerar posibles lesiones asociadas durante la fase aguda para lograr resultados óptimos a corto, mediano y largo plazo para nuestros pacientes. Un enfoque integral y proactivo del diagnóstico y tratamiento es vital para abordar eficazmente esta patología y minimizar sus posibles secuelas.


Assuntos
Ligamento Colateral Ulnar , Luxações Articulares , Articulação Metacarpofalângica , Polegar , Humanos , Articulação Metacarpofalângica/lesões , Articulação Metacarpofalângica/cirurgia , Feminino , Luxações Articulares/cirurgia , Idoso , Polegar/lesões , Polegar/cirurgia , Ligamento Colateral Ulnar/lesões , Ligamento Colateral Ulnar/cirurgia
10.
Int J Biol Macromol ; 272(Pt 2): 132705, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38810850

RESUMO

Trypanosoma cruzi is the causative agent of Chagas disease, as well as a trypanosomatid parasite with a complex biological cycle that requires precise mechanisms for regulating gene expression. In Trypanosomatidae, gene regulation occurs mainly at the mRNA level through the recognition of cis elements by RNA-binding proteins (RBPs). Alba family members are ubiquitous DNA/RNA-binding proteins with representatives in trypanosomatid parasites functionally related to gene expression regulation. Although T. cruzi possesses two groups of Alba proteins (Alba1/2 and Alba30/40), their functional role remains poorly understood. Thus, herein, a characterization of T. cruzi Alba (TcAlba) proteins was undertaken. Physicochemical, structural, and phylogenetic analysis of TcAlba showed features compatible with RBPs, such as hydrophilicity, RBP domains/motifs, and evolutionary conservation of the Alba-domain, mainly regarding other trypanosomatid Alba. However, in silico RNA interaction analysis of T. cruzi Alba proteins showed that TcAlba30/40 proteins, but not TcAlba1/2, would directly interact with the assayed RNA molecules, suggesting that these two groups of TcAlba proteins have different targets. Given the marked differences existing between both T. cruzi Alba groups (TcAlba1/2 and TcAlba30/40), regarding sequence divergence, RNA binding potential, and life-cycle expression patterns, we suggest that they would be involved in different biological processes.

11.
Cir Pediatr ; 37(2): 50-54, 2024 Apr 01.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-38623796

RESUMO

INTRODUCTION: The course in Primary Care in Pediatric Trauma (ATIP in Spanish) has been taught in Spain since 1997, and there are currently 9 accredited training centers. Care of polytraumatized pediatric patients often takes place in an environment conducive to errors resulting from forgetfulness, which is why checklists - mnemonic tools widely used in industry and medicine - are particularly useful to avoid such errors. Although several checklists exist for pediatric trauma care, none have been developed within the setting of our course. MATERIALS AND METHODS: The criteria for being selected as an expert in Primary Care in Pediatric Trauma were agreed upon with the scientific polytrauma committee of the Spanish Pediatric Surgery Society. The items that make up the checklist were obtained from a review of the literature and consultation with selected experts, using the Delphi Technique. RESULTS: 10 experts representing the 9 groups or training centers in Primary Care in Pediatric Trauma were selected, and a 28-item checklist was drawn up in accordance with their design recommendations. CONCLUSIONS: With the consensus of all the groups, a checklist for the treatment of polytraumatized pediatric patients was drawn up using the Delphi Technique, an essential requirement for the dissemination of this checklist, which should be adapted and validated for use in each healthcare center.


INTRODUCCION: El curso de Asistencia Inicial al Trauma Pediátrico se imparte en España desde 1997, existiendo en la actualidad 9 centros formadores acreditados. La asistencia al paciente pediátrico politraumatizado se produce muchas veces en un ambiente proclive al error por olvido, por lo que las listas de verificación, como herramientas mnemotécnicas de amplia difusión en la industria y en medicina, serían especialmente útiles para evitarlos. Aunque existen varias listas de verificación para la asistencia al traumatismo pediátrico, ninguna se ha desarrollado en el entorno de nuestro curso. MATERIAL Y METODOS: Se acordaron los criterios para ser seleccionado como experto en Asistencia Inicial al Trauma Pediátrico con la comisión científica de politrauma de la Sociedad Española de Cirugía Pediátrica. Los ítems para formar la lista de verificación se obtuvieron a partir de una revisión bibliográfica y de la consulta a los expertos seleccionados, empleando un método Delphi. RESULTADOS: Se seleccionaron 10 expertos que representan los 9 grupos o centros formadores en Asistencia Inicial al Trauma Pediátrico y se elaboró una lista de verificación con 28 ítems, siguiendo sus recomendaciones de diseño. CONCLUSIONES: Se diseñó una lista de verificación para el manejo del paciente pediátrico politraumatizado, con el consenso de todos los grupos empleando un método Delphi, requisito fundamental para facilitar la difusión de esta lista. Sería preciso adaptar y validar dicha lista para su uso en cada centro asistencial.


Assuntos
Lista de Checagem , Traumatismo Múltiplo , Humanos , Criança , Técnica Delphi , Consenso , Atenção Primária à Saúde
12.
Front Plant Sci ; 15: 1331269, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38576790

RESUMO

MADS-domain transcription factors play pivotal roles in numerous developmental processes in Arabidopsis thaliana. While their involvement in flowering transition and floral development has been extensively examined, their functions in root development remain relatively unexplored. Here, we explored the function and genetic interaction of three MADS-box genes (XAL2, SOC1 and AGL24) in primary root development. By analyzing loss-of-function and overexpression lines, we found that SOC1 and AGL24, both critical components in flowering transition, redundantly act as repressors of primary root growth as the loss of function of either SOC1 or AGL24 partially recovers the primary root growth, meristem cell number, cell production rate, and the length of fully elongated cells of the short-root mutant xal2-2. Furthermore, we observed that the simultaneous overexpression of AGL24 and SOC1 leads to short-root phenotypes, affecting meristem cell number and fully elongated cell size, whereas SOC1 overexpression is sufficient to affect columella stem cell differentiation. Additionally, qPCR analyses revealed that these genes exhibit distinct modes of transcriptional regulation in roots compared to what has been previously reported for aerial tissues. We identified 100 differentially expressed genes in xal2-2 roots by RNA-seq. Moreover, our findings revealed that the expression of certain genes involved in cell differentiation, as well as stress responses, which are either upregulated or downregulated in the xal2-2 mutant, reverted to WT levels in the absence of SOC1 or AGL24.

13.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-38642735

RESUMO

Osteoporosis, and the consequences derived from it, such as fragility fractures, constitute a growing public health problem. Suffering from a fracture of this nature is the main risk factor for suffering a new fracture. It is documented that vertebral compression fractures lead to significant morbidity and mortality, in the short and long term, as well as other complications, such as sagittal imbalance and hyperkyphosis of the segment. However, we have not found documentation that analyzes the medium and long-term consequences of these injuries, assessing the type of treatment used, and the economic impact they represent. The purpose of this review is to analyze the main recent literature on the subject and make a breakdown of the consequences of these fractures in various spheres, such as economic, quality of life, sagittal balance and radiographic parameters, pain or mortality; as well as a brief analysis of epidemiology and natural history. CONCLUSION: Osteoporotic fractures constitute an emerging problem, both in the medical and economic fields. The consequences and sequelae on the patient are multiple and although surgical options offer good long-term results, it is necessary to properly select the patient, through multidisciplinary teams, to try to minimize potential complications.

14.
J Clin Oncol ; : JCO2301983, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38657187

RESUMO

PURPOSE: The anti-NECTIN4 antibody-drug conjugate enfortumab vedotin (EV) is approved for patients with metastatic urothelial cancer (mUC). However, durable benefit is only achieved in a small, yet uncharacterized patient subset. NECTIN4 is located on chromosome 1q23.3, and 1q23.3 gains represent frequent copy number variations (CNVs) in urothelial cancer. Here, we aimed to evaluate NECTIN4 amplifications as a genomic biomarker to predict EV response in patients with mUC. MATERIALS AND METHODS: We established a NECTIN4-specific fluorescence in situ hybridization (FISH) assay to assess the predictive value of NECTIN4 CNVs in a multicenter EV-treated mUC patient cohort (mUC-EV, n = 108). CNVs were correlated with membranous NECTIN4 protein expression, EV treatment responses, and outcomes. We also assessed the prognostic value of NECTIN4 CNVs measured in metastatic biopsies of non-EV-treated mUC (mUC-non-EV, n = 103). Furthermore, we queried The Cancer Genome Atlas (TCGA) data sets (10,712 patients across 32 cancer types) for NECTIN4 CNVs. RESULTS: NECTIN4 amplifications are frequent genomic events in muscle-invasive bladder cancer (TCGA bladder cancer data set: approximately 17%) and mUC (approximately 26% in our mUC cohorts). In mUC-EV, NECTIN4 amplification represents a stable genomic alteration during metastatic progression and associates with enhanced membranous NECTIN4 protein expression. Ninety-six percent (27 of 28) of patients with NECTIN4 amplifications demonstrated objective responses to EV compared with 32% (24 of 74) in the nonamplified subgroup (P < .001). In multivariable Cox analysis adjusted for age, sex, and Bellmunt risk factors, NECTIN4 amplifications led to a 92% risk reduction for death (hazard ratio, 0.08 [95% CI, 0.02 to 0.34]; P < .001). In the mUC-non-EV, NECTIN4 amplifications were not associated with outcomes. TCGA Pan-Cancer analysis demonstrated that NECTIN4 amplifications occur frequently in other cancers, for example, in 5%-10% of breast and lung cancers. CONCLUSION: NECTIN4 amplifications are genomic predictors of EV responses and long-term survival in patients with mUC.

15.
Cell Genom ; 4(4): 100528, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38552621

RESUMO

Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) enzymes mutate specific DNA sequences and hairpin-loop structures, challenging the distinction between passenger and driver hotspot mutations. Here, we characterized 115 whole genomes of metastatic urothelial carcinoma (mUC) to identify APOBEC mutagenic hotspot drivers. APOBEC-associated mutations were detected in 92% of mUCs and were equally distributed across the genome, while APOBEC hotspot mutations (ApoHMs) were enriched in open chromatin. Hairpin loops were frequent targets of didymi (twins in Greek), two hotspot mutations characterized by the APOBEC SBS2 signature, in conjunction with an uncharacterized mutational context (Ap[C>T]). Next, we developed a statistical framework that identified ApoHMs as drivers in coding and non-coding genomic regions of mUCs. Our results and statistical framework were validated in independent cohorts of 23 non-metastatic UCs and 3,744 samples of 17 metastatic cancers, identifying cancer-type-specific drivers. Our study highlights the role of APOBEC in cancer development and may contribute to developing novel targeted therapy options for APOBEC-driven cancers.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Carcinoma de Células de Transição/genética , Neoplasias da Bexiga Urinária/genética , Mutagênese/genética , Mutação/genética , Mapeamento Cromossômico
16.
Artigo em Inglês | MEDLINE | ID: mdl-38509439

RESUMO

INTRODUCTION: Bats are a diverse group of mammals that have unique features allowing them to act as reservoir hosts for several zoonotic pathogens such as Leptospira. Leptospires have been classified into pathogenic, intermediate, and saprophytic groups and more recently into clades P1, P2, S1, and S2, being all the most important pathogenic species related to leptospirosis included within the P1/pathogenic clade. Leptospira has been detected from bats in several regions worldwide; however, the diversity of leptospires harboured by bats is still unknown. AIM: The aim of the present study was to determine the genetic diversity of Leptospira spp. harboured by bats worldwide. METHODS: A systematic review was conducted on four databases to retrieve studies in which Leptospira was detected from bats. All studies were screened to retrieve all available Leptospira spp. 16S rRNA sequences from the GenBank database and data regarding their origin. Sequences obtained were compared with each other and reference sequences of Leptospira species and analysed through phylogenetic analysis. RESULTS: A total of 418 Leptospira spp. 16S rRNA sequences isolated from 55 bat species from 14 countries were retrieved from 15 selected manuscripts. From these, 417 sequences clustered within the P1/pathogenic group, and only one sequence clustered within the P2/intermediate group. Six major clades of P1/pathogenic Leptospira spp. were identified, three of them composed exclusively of sequences obtained from bats. CONCLUSION: We identified that bats harbour a great genetic diversity of Leptospira spp. that form part of the P1/pathogenic clade, some of which are closely related to leptospirosis-associated species. This finding contributes to the knowledge of the diversity of leptospires hosted by bats worldwide and reinforces the role of bats as reservoirs of P1/pathogenic Leptospira spp.

17.
J Environ Manage ; 356: 120638, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38518496

RESUMO

Microorganisms drive the degradation of organic matter thanks to their enzymatic versatility. However, the structure of lignocellulose poses a great challenge for the microbiota inhabiting a compost pile. Our purpose was to increase the biodegradability of vegetable waste in the early stages of the composting process by applying a microbial consortium with lignocelllulolytic capacity. For this, a previous screening was performed among the culturable microbiota from different composting processes to find inoculants with ligninocellulolytic activity. Selected strains were applied as a pure culture and as a microbial consortium. The starting material was composed of tomato plant and pruning remains mixed in a ratio (50:50 v/v), whose humidity was adjusted to around 65%. To determine the ability of both treatments to activate the biodegradation of the mixtures, moisture, organic matter, ash, C/N ratio, 4-day cumulative respirometric index (AT4) and degradation rates of cellulose, hemicellulose and lignin were evaluated. Subsequently, a real composting process was developed in which the performance of the microbial consortium was compared with the composting process without inoculum (control). According to our tests, three microbial strains (Bacillus safensis, Bacillus licheniformis and Fusarium oxysporum) were selected. The results showed that the application of the bacteria strains at low doses (104 CFU g-1 on the complete residual material of the pile) resulted in higher rates of lignocelullose degradation after 10 days of treatment compared to that observed after application of the fungus in pure culture or untreated controls. The implementation of the strategy described in this work resulted in obtaining compost with better agronomic quality than the uninoculated controls. Therefore, the application of this consortium could be considered as an interesting tool for bioactivation of lignocellulosic waste prior to the composting process.


Assuntos
Compostagem , Lignina , Lignina/metabolismo , Celulose , Bactérias/metabolismo , Solo
18.
Public Health ; 230: 12-20, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38479163

RESUMO

OBJECTIVE: This article aims to estimate the differences in environmental impact (greenhouse gas [GHG] emissions, land use, energy used, acidification and potential eutrophication) after one year of promoting a Mediterranean diet (MD). METHODS: Baseline and 1-year follow-up data from 5800 participants in the PREDIMED-Plus study were used. Each participant's food intake was estimated using validated semi-quantitative food frequency questionnaires, and the adherence to MD using the Dietary Score. The influence of diet on environmental impact was assessed through the EAT-Lancet Commission tables. The influence of diet on environmental impact was assessed through the EAT-Lancet Commission tables. The association between MD adherence and its environmental impact was calculated using adjusted multivariate linear regression models. RESULTS: After one year of intervention, the kcal/day consumed was significantly reduced (-125,1 kcal/day), adherence to a MD pattern was improved (+0,9) and the environmental impact due to the diet was significantly reduced (GHG: -361 g/CO2-eq; Acidification:-11,5 g SO2-eq; Eutrophication:-4,7 g PO4-eq; Energy use:-842,7 kJ; and Land use:-2,2 m2). Higher adherence to MD (high vs. low) was significantly associated with lower environmental impact both at baseline and one year follow-up. Meat products had the greatest environmental impact in all the factors analysed, both at baseline and at one-year follow-up, in spite of the reduction observed in their consumption. CONCLUSIONS: A program promoting a MD, after one year of intervention, significantly reduced the environmental impact in all the factors analysed. Meat products had the greatest environmental impact in all the dimensions analysed.


Assuntos
Dieta Mediterrânea , Gases de Efeito Estufa , Humanos , Dieta , Meio Ambiente , Coleta de Dados
19.
Hernia ; 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38503978

RESUMO

INTRODUCTION: There has been a rapid proliferation of the robotic approach to inguinal hernia, mainly in the United States, as it has shown similar outcomes to the laparoscopic approach but with a significant increase in associated costs. Our objective is to conduct a cost analysis in our setting (Spanish National Health System). MATERIALS AND METHODS: A retrospective single-center comparative study on inguinal hernia repair using a robotic approach versus laparoscopic approach. RESULTS: A total of 98 patients who underwent either robotic or laparoscopic TAPP inguinal hernia repair between October 2021 and July 2023 were analyzed. Out of these 98 patients, 20 (20.4%) were treated with the robotic approach, while 78 (79.6%) underwent the laparoscopic approach. When comparing both approaches, no significant differences were found in terms of complications, recurrences, or readmissions. However, the robotic group exhibited a longer surgical time (86 ± 33.07 min vs. 40 ± 14.46 min, p < 0.001), an extended hospital stays (1.6 ± 0.503 days vs. 1.13 ± 0.727 days, p < 0.007), as well as higher procedural costs (2318.63 ± 205.15 € vs. 356.81 ± 110.14 €, p < 0.001) and total hospitalization costs (3272.48 ± 408.49 € vs. 1048.61 ± 460.06 €, p < 0.001). These results were consistent when performing subgroup analysis for unilateral and bilateral hernias. CONCLUSIONS: The benefits observed in terms of recurrence rates and post-surgical complications do not justify the additional costs incurred by the robotic approach to inguinal hernia within the national public healthcare system. Nevertheless, it represents a simpler way to initiate the robotic learning curve, justifying its use in a training context.

20.
Curr Biol ; 34(8): 1646-1656.e4, 2024 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-38518777

RESUMO

The obesity epidemic is principally driven by the consumption of more calories than the body requires. It is therefore essential that the mechanisms underpinning feeding behavior are defined. Neurons within the brainstem dorsal vagal complex (DVC) receive direct information from the digestive system and project to second-order regions in the brain to regulate food intake. Although γ-aminobutyric acid is expressed in the DVC (GABADVC), its function in this region has not been defined. In order to discover the unique gene expression signature of GABADVC cells, we used single-nucleus RNA sequencing (Nuc-seq), and this revealed 19 separate clusters. We next probed the function of GABADVC cells and discovered that the selective activation of GABADVC neurons significantly controls food intake and body weight. Optogenetic interrogation of GABADVC circuitry identified GABADVC → hypothalamic arcuate nucleus (ARC) projections as appetite suppressive without creating aversion. Electrophysiological analysis revealed that GABADVC → ARC stimulation inhibits hunger-promoting neuropeptide Y (NPY) neurons via GABA release. Adopting an intersectional genetics strategy, we clarify that the GABADVC → ARC circuit curbs food intake. These data identify GABADVC as a new modulator of feeding behavior and body weight and a controller of orexigenic NPY neuron activity, thereby providing insight into the neural underpinnings of obesity.


Assuntos
Núcleo Arqueado do Hipotálamo , Tronco Encefálico , Comportamento Alimentar , Núcleo Arqueado do Hipotálamo/metabolismo , Núcleo Arqueado do Hipotálamo/fisiologia , Animais , Tronco Encefálico/fisiologia , Tronco Encefálico/metabolismo , Camundongos , Masculino , Comportamento Alimentar/fisiologia , Neurônios GABAérgicos/fisiologia , Neurônios GABAérgicos/metabolismo , Ácido gama-Aminobutírico/metabolismo , Ingestão de Alimentos/fisiologia , Camundongos Endogâmicos C57BL , Feminino
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