Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 556
Filtrar
Mais filtros

Intervalo de ano de publicação
1.
Proc Natl Acad Sci U S A ; 119(15): e2118740119, 2022 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-35394879

RESUMO

Mutations in mitochondrial DNA (mtDNA) contribute to multiple diseases. However, how new mtDNA mutations arise and accumulate with age remains understudied because of the high error rates of current sequencing technologies. Duplex sequencing reduces error rates by several orders of magnitude via independently tagging and analyzing each of the two template DNA strands. Here, using duplex sequencing, we obtained high-quality mtDNA sequences for somatic tissues (liver and skeletal muscle) and single oocytes of 30 unrelated rhesus macaques, from 1 to 23 y of age. Sequencing single oocytes minimized effects of natural selection on germline mutations. In total, we identified 17,637 tissue-specific de novo mutations. Their frequency increased ∼3.5-fold in liver and ∼2.8-fold in muscle over the ∼20 y assessed. Mutation frequency in oocytes increased ∼2.5-fold until the age of 9 y, but did not increase after that, suggesting that oocytes of older animals maintain the quality of their mtDNA. We found the light-strand origin of replication (OriL) to be a hotspot for mutation accumulation with aging in liver. Indeed, the 33-nucleotide-long OriL harbored 12 variant hotspots, 10 of which likely disrupt its hairpin structure and affect replication efficiency. Moreover, in somatic tissues, protein-coding variants were subject to positive selection (potentially mitigating toxic effects of mitochondrial activity), the strength of which increased with the number of macaques harboring variants. Our work illuminates the origins and accumulation of somatic and germline mtDNA mutations with aging in primates and has implications for delayed reproduction in modern human societies.


Assuntos
Envelhecimento , Mitocôndrias , Mutação , Oócitos , Animais , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Humanos , Macaca mulatta/genética , Mitocôndrias/genética , Oócitos/metabolismo
2.
Br J Haematol ; 205(1): 109-121, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38811363

RESUMO

Circulating tumour DNA (ctDNA) allows genotyping and minimal residual disease (MRD) detection in lymphomas. Using a next-generation sequencing (NGS) approach (EuroClonality-NDC), we evaluated the clinical and prognostic value of ctDNA in a series of R-CHOP-treated diffuse large B-cell lymphoma (DLBCL) patients at baseline (n = 68) and after two cycles (n = 59), monitored by metabolic imaging (positron emission tomography combined with computed tomography [PET/CT]). A molecular marker was identified in 61/68 (90%) ctDNA samples at diagnosis. Pretreatment high ctDNA levels significantly correlated with elevated lactate dehydrogenase, advanced stage, high-risk International Prognostic Index and a trend to shorter 2-year progression-free survival (PFS). Valuable NGS data after two cycles of treatment were obtained in 44 cases, and 38 achieved major molecular response (MMR; 2.5-log drop in ctDNA). PFS curves displayed statistically significant differences among those achieving MMR versus those not achieving MMR (2-year PFS of 76% vs. 0%, p < 0.001). Similarly, more than 66% reduction in ΔSUVmax by PET/CT identified two subgroups with different prognosis (2-year PFS of 83% vs. 38%; p < 0.001). Combining both approaches MMR and ΔSUVmax reduction, a better stratification was observed (2-year PFS of 84% vs. 17% vs. 0%, p < 0.001). EuroClonality-NDC panel allows the detection of a molecular marker in the ctDNA in 90% of DLBCL. ctDNA reduction at two cycles and its combination with interim PET results improve patient prognosis stratification.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , DNA Tumoral Circulante , Linfoma Difuso de Grandes Células B , Neoplasia Residual , Humanos , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/sangue , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Neoplasia Residual/diagnóstico , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Adulto , DNA Tumoral Circulante/sangue , DNA Tumoral Circulante/genética , Biópsia Líquida/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Idoso de 80 Anos ou mais , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Rituximab/uso terapêutico , Rituximab/administração & dosagem , Ciclofosfamida/uso terapêutico , Ciclofosfamida/administração & dosagem , Biomarcadores Tumorais/sangue , Vincristina/uso terapêutico , Vincristina/administração & dosagem , Prognóstico , Doxorrubicina/uso terapêutico , Doxorrubicina/administração & dosagem , Sequenciamento de Nucleotídeos em Larga Escala , Prednisona/uso terapêutico , Prednisona/administração & dosagem
3.
Breast Cancer Res Treat ; 205(3): 475-485, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38453782

RESUMO

PURPOSE: The prognostic utility and biological correlates of neutrophil to lymphocyte ratio (NLR), a potential biomarker of the balance between immune response and the inflammatory status, are still uncertain in breast cancer (BC). METHODS: We analysed a cohort of 959 women with early breast cancer, mostly treated with neoadjuvant or adjuvant chemotherapy. Clinical and pathological data, survival, NLR (continuous and categorical) and stromal tumor infiltrating lymphocytes (sTIL) were evaluated. RESULTS: NLR was only weakly associated with Ki67, while no association was found for grade, histology, immunohistochemical subtype or stage. Lymphocyte infiltration of the tumor did not correlate with NLR (Rho: 0.05, p = 0.30). These results were similar in the whole group and across the different BC subtypes, with no differences in triple negative BC. Relapse free interval (RFI), breast cancer specific survival (BCSS) and overall survival (OS) changed according to pre-treatment NLR neither in the univariate nor in the multivariate Cox models (RFI: HR 0.948, p = 0.61; BCSS: HR 0.920, p = 0.57; OS: HR 0.96, p = 0.59). CONCLUSION: These results question the utility of NLR as a prognostic biomarker in early breast cancer and suggest the lack of correlation of NLR with tumor microenvironment immune response.


Assuntos
Neoplasias da Mama , Linfócitos do Interstício Tumoral , Linfócitos , Neutrófilos , Humanos , Feminino , Neutrófilos/imunologia , Prognóstico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Neoplasias da Mama/imunologia , Neoplasias da Mama/sangue , Pessoa de Meia-Idade , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos/metabolismo , Linfócitos/imunologia , Idoso , Adulto , Biomarcadores Tumorais , Estadiamento de Neoplasias , Contagem de Linfócitos
4.
Nicotine Tob Res ; 26(6): 780-784, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38097340

RESUMO

INTRODUCTION: E-cigarettes and heated tobacco products (HTPs) may serve as potential options for harm reduction for smokers if they possess reward profiles similar to cigarettes. Little is known about the abuse liability of HTPs and e-cigarettes versus cigarettes in racial/ethnic minority smokers. AIMS AND METHODS: Twenty-two nicotine-deprived people who smoke (black [n = 12] and white [n = 10]) completed three visits that included a standardized 10-puff bout followed by a 50-minute ad libitum use assessment with their usual brand cigarette (UBC), an e-cigarette, and HTP. Visits were completed in a randomized crossover design and were separated by a minimum 48-hour washout period. Assessments included plasma nicotine, Cmax, and reductions in craving and withdrawal. RESULTS: UBC delivered significantly greater levels of nicotine compared to the e-cigarette (p < .001) and HTP (p < .01) during both the standardized and ad libitum sessions. HTP delivered more nicotine than the e-cigarette during the standardized puffing session (p = .047) but not the ad libitum session. Only craving during the standardized puffing session and not the ad libitum session showed significant differences across products (p < .001) such that UBC resulted in the greatest reduction followed by HTP and e-cigarette. CONCLUSIONS: Despite greater nicotine delivery from the UBC compared to e-cigarette and HTP, participants reported reductions in craving and withdrawal across products, particularly following ad libitum use. IMPLICATIONS: Use of participant's UBCs (UBC) resulted in greater nicotine delivery compared to both the e-cigarette and HTP. Despite this relative difference in nicotine delivery, participants reported reductions in craving and withdrawal across products, particularly following ad libitum use. These findings suggest that in this sample of black and white people who smoke, HTPs and e-cigarettes provided significant relief from negative symptoms that maintain smoking.


Assuntos
Fumar Cigarros , Sistemas Eletrônicos de Liberação de Nicotina , Nicotina , Síndrome de Abstinência a Substâncias , Produtos do Tabaco , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Negro ou Afro-Americano/psicologia , Negro ou Afro-Americano/estatística & dados numéricos , População Negra/estatística & dados numéricos , População Negra/psicologia , Fissura , Estudos Cross-Over , Sistemas Eletrônicos de Liberação de Nicotina/estatística & dados numéricos , Temperatura Alta , Nicotina/administração & dosagem , Fumantes/psicologia , Fumantes/estatística & dados numéricos , Abandono do Hábito de Fumar/métodos , Abandono do Hábito de Fumar/psicologia , População Branca/psicologia , População Branca/estatística & dados numéricos
5.
J Clin Lab Anal ; 38(13-14): e25083, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39105399

RESUMO

BACKGROUND: LIPA, situated on chromosome 10q23.2-q23.3, encodes the enzyme lysosomal acid lipase (LAL) (EC 3.1.1.13). Genetic alterations in LIPA lead to lysosomal acid lipase deficiency (LALD), an inborn error causing lipid metabolism anomalies and impairing cholesterol and triacylglyceride degradation. Over 40 LIPA variants have been documented, yet this study focuses on just two. The rs1051338 variant (NM_000235:c.46A>C) affects the signal peptide in Exon 2, whereas rs116928232, located in Exon 8, alters the splice site (NM_000235:c.894G>A), impacting lysosomal acid lipase activity. Considering the diverse clinical manifestations of LALD and the rising hepatic steatosis prevalence in Mexican population, mainly due to diet, these variants were investigated within this demographic to uncover potential contributing factors. This study aimed to reveal the frequency of rs1051338 and rs116928232 among healthy mestizo individuals in Northwest Mexico, marking a significant genetic exploration in this demographic. METHODS: Three hundred ten healthy mestizo individuals underwent PCR-RFLP analysis for both variants, and Sanger sequencing was performed for variant rs116928232. Bioinformatic analysis was also performed to predict protein changes. RESULTS: Allele frequencies for rs1051338 (FA = 0.39, p value = 0.15) and rs116928232 (FA = 0.0016, p value = 0.49) aligned with reported data, while bioinformatic analysis allowed us to identify the protein alteration observed in both variants; finally, the variants showed no linkage between them (normalized D' = 1.03, p value = 0.56). CONCLUSIONS: Allelic frequencies closely matched reported data, and protein structure analysis confirmed variant impacts on LAL enzyme function. Notably, this study marks the first analysis of rs1051338 and rs116928232 in a healthy Mexican mestizo population.


Assuntos
Frequência do Gene , Polimorfismo de Nucleotídeo Único , Esterol Esterase , Humanos , México/epidemiologia , Masculino , Feminino , Esterol Esterase/genética , Adulto , Polimorfismo de Nucleotídeo Único/genética , Pessoa de Meia-Idade , Adulto Jovem
6.
Sensors (Basel) ; 24(4)2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38400299

RESUMO

Studying soil composition is vital for agricultural and edaphology disciplines. Presently, colorimetry serves as a prevalent method for the on-site visual examination of soil characteristics. However, this technique necessitates the laboratory-based analysis of extracted soil fragments by skilled personnel, leading to substantial time and resource consumption. Contrastingly, sensor techniques effectively gather environmental data, though they mostly lack in situ studies. Despite this, sensors offer substantial on-site data generation potential in a non-invasive manner and can be included in wireless sensor networks. Therefore, the aim of the paper is to develop a low-cost red, green, and blue (RGB)-based sensor system capable of detecting changes in the composition of the soil. The proposed sensor system was found to be effective when the sample materials, including salt, sand, and nitro phosphate, were determined under eight different RGB lights. Statistical analyses showed that each material could be classified with significant differences based on specific light variations. The results from a discriminant analysis documented the 100% prediction accuracy of the system. In order to use the minimum number of colors, all the possible color combinations were evaluated. Consequently, a combination of six colors for salt and nitro phosphate successfully classified the materials, whereas all the eight colors were found to be effective for classifying sand samples. The proposed low-cost RGB sensor system provides an economically viable and easily accessible solution for soil classification.

7.
Sensors (Basel) ; 24(6)2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38544137

RESUMO

This paper presents an innovative dataset designed explicitly for challenging agricultural environments, such as greenhouses, where precise location is crucial, but GNNS accuracy may be compromised by construction elements and the crop. The dataset was collected using a mobile platform equipped with a set of sensors typically used in mobile robots as it was moved through all the corridors of a typical Mediterranean greenhouse featuring tomato crops. This dataset presents a unique opportunity for constructing detailed 3D models of plants in such indoor-like spaces, with potential applications such as robotized spraying. For the first time, to the authors' knowledge, a dataset suitable to test simultaneous localization and mapping (SLAM) methods is presented in a greenhouse environment, which poses unique challenges. The suitability of the dataset for this purpose is assessed by presenting SLAM results with state-of-the-art algorithms. The dataset is available online.

8.
J Environ Manage ; 357: 120840, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38583381

RESUMO

Agriculture and livestock farming are activities that depend on energy consumption. Photovoltaic self-consumption systems can reduce the production costs of these actors, especially in periods of high-energy price volatility. This work aimed to determine the degree of implementation of photovoltaic self-consumption systems, their relationship with the economic impact of the energy crisis, and the perception of producers to use renewable energy sources in the Spanish agricultural system as it is one of the most important at European level. For this purpose, a survey of the Spanish agricultural and livestock system, involving 396 primary producers, was carried out between December 2022 and March 2023. The results suggest that self-consumption systems are in place in 49.1% of all farms and that these have had a positive effect in alleviating the rising energy costs suffered by the Spanish primary sector. In summary, Spanish primary producers generally have a favorable perception of the use of renewable energies on their farms, especially photovoltaic. However, the cluster analysis shows the fact that there are two types of producers, active and passive, from an environmental point of view. The characterization of this type of producers can help the Spanish Administration to improve the efficiency of its energy strategy, and can be a source of inspiration for the governments of other countries.


Assuntos
Agricultura , Percepção , Agricultura/métodos , Fazendas , Energia Renovável
9.
Vet Radiol Ultrasound ; 65(4): 344-351, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38572892

RESUMO

The conformation of spinal arachnoid diverticula (SAD) and their clinical implications are poorly characterized in dogs. This retrospective cross-sectional study describes different SAD conformations in dogs and aims to identify if there is an association between SAD conformation and clinical features, localization, syringomyelia (SM) presence, concurrent vertebral condition, treatment option, and short as well as long-term outcome. Sixty-two dogs were included (12 cervical and 50 thoracolumbar SAD). All dogs with a cervical SAD had a cranial tethered conformation and were not included in the statistical analysis. Half of the dogs with a thoracolumbar SAD were cranial tethered, and the other half were caudal tethered. SM associated with SAD had a moderate prevalence in the cervical region (58.3%) and a high prevalence in the thoracolumbar region (82%). All dogs with the presence of SM and caudal tethered SAD had a cranial positioned SM, and all dogs with SM and a cranial tethered SAD had a caudal positioned SM. The SM absolute length and SM length/L2 ratio were significantly higher (P = .018, respectively) in the caudal tethered SAD compared with the cranial tethered SAD. The short-term outcome was statistically different (P = .045) between caudal and cranial tethered thoracolumbar SAD, but not the long-term outcome (P = .062). Multivariable logistic regression identified thoracolumbar caudal tethered SAD conformation had a better short-term outcome (P = 0.017, OR: 0.043, CI: 0.003-0.563), independently of SM length measurements. SAD conformation in dogs can influence SM formation. A possible link between short-term outcome and SAD conformation was found, but further research is warranted.


Assuntos
Doenças do Cão , Cães , Animais , Doenças do Cão/diagnóstico por imagem , Doenças do Cão/patologia , Estudos Retrospectivos , Estudos Transversais , Feminino , Masculino , Cistos Aracnóideos/veterinária , Cistos Aracnóideos/diagnóstico por imagem , Siringomielia/veterinária , Siringomielia/diagnóstico por imagem , Divertículo/veterinária , Divertículo/diagnóstico por imagem , Aracnoide-Máter/patologia , Aracnoide-Máter/diagnóstico por imagem , Relevância Clínica
10.
Rev Esp Enferm Dig ; 1192024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39235188

RESUMO

Pseudolipomatosis (PL) is a rare, benign, iatrogenic condition first described in colorectal mucosa. This condition is thought to arise from gas penetration into the mucosa due to mechanical or chemical injury during endoscopy. Despite these associations and its characteristic appearence, the definitive pathogenesis remains unclear and it continues to be underrecognized by some pathologists and endoscopists, which is crucial to avoid any further unnecessary treatments. Immunohistochemistry techniques play a role in differentiating PL from similar conditions such as cystic intestinal pneumatosis, intestinal lipomatosis, or lymphangiectasia. A 70-year-old man with a family history of colon adenocarcinoma was diagnosed with duodenal pseudolipomatosis after a routine endoscopic assessment. To the best of our knowledge, there have been only two reports of PL diagnosed in the duodenum. A review of over 500 duodenal biopsies at our centre revealed that no other instances were identified, emphasizing the unusual occurrence of this particular location.

11.
Clin Psychol Psychother ; 31(3): e2997, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38747373

RESUMO

CONTEXT: Several studies have shown that emotional regulation (ER) is a transdiagnostic construct of emotional disorders. Therefore, if therapy improves ER, it would improve psychological distress. OBJECTIVE: This review assesses and compares the changes in ER due to psychological treatment in different therapies. METHODS: A systematic review and meta-analysis of RCTs published in the databases PubMed, PsycINFO and Web of Science was performed. It was registered in PROSPERO under the number CRD42023387317. Two independent experts in the field reviewed the articles. RESULTS: A total of 18 articles met the criteria for inclusion in the review. Analysis of these studies suggests that in unified protocol (UP), cognitive behaviour therapy, dialectical behaviour therapy (DBT) and mindfulness, there is evidence to support that a moderate effect occurs during treatment. Furthermore, in mindfulness and DBT, the effect was moderate in the follow-up period, while in UP, it was high. LIMITATIONS: Given the heterogeneity of the applied interventions and the methodological limitations found in the reviewed trials, the results should be interpreted with caution. CONCLUSIONS: UP, cognitive behaviour therapy, DBT and mindfulness can improve ER after therapy, while UP, DBT and mindfulness in the follow-up period. Other therapies, such as SKY or Flotation REST, require more research.


INTRODUCCIÓN: Varios estudios han demostrado que la regulación emocional es un constructo transdiagnóstico de los trastornos emocionales. Por lo tanto, si la terapia mejora la regulación emocional, también mejorará el malestar psicológico. OBJETIVO: Evaluar y comparar el cambio en la regulación emocional debido al tratamiento psicológico en diferentes terapias. MÉTODO: Se realizó una revisión sistemática y metaanálisis de ECA publicados en las bases de datos PubMed, PsycINFO y Web of Science. Se registró en PROSPERO con el número CRD42023387317. Dos expertos independientes en la materia revisaron los artículos. RESULTADOS: Un total de 18 artículos cumplieron los criterios de inclusión en la revisión. El análisis de estos estudios sugiere que en el Protocolo Unificado, la Terapia Cognitivo Conductual, la Terapia Dialéctica Conductual y terapias basadas en mindfulness existen evidencias que apoyan que se produce un efecto moderado durante el tratamiento. Además, en las terapias basadas en mindfulness y en la Terapia Dialéctica Conductual, el efecto se moduló en el periodo de seguimiento, mientras que en el Protocolo Unificado fue mayor. LIMITACIONES: Dada la heterogeneidad de las intervenciones aplicadas y las limitaciones metodológicas encontradas en los ensayos revisados, los resultados podrán interpretarse con cautela. CONCLUSIONES: UP, CBT, DBT y mindfulness pueden mejorar la ER tras la terapia, mientras que UP, DBT y mindfulness pueden mejorar la recuperación tras un tiempo de seguimiento. Otras terapias, como SKY o Flotation REST, requieren más investigación.


Assuntos
Terapia Cognitivo-Comportamental , Regulação Emocional , Atenção Plena , Humanos , Atenção Plena/métodos , Terapia Cognitivo-Comportamental/métodos , Terapia do Comportamento Dialético/métodos
12.
Br J Haematol ; 202(4): 776-784, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37386877

RESUMO

The aims of our study were to analyse compliance with the 2014 GELTAMO SMZL Guidelines, in patients with splenic marginal zone lymphoma (SMZL), and to evaluate the outcome according to the HPLLs/ABC-adapted therapeutic strategy. Observational prospective multicenter study of 181 SMZL patients diagnosed between 2014 and 2020. Lymphoma-specific survival (LSS), composite event-free survival (CEFS) and response rates were assessed. 57% of the 168 patients included in the analysis followed the Guidelines. The overall response rate was higher in the rituximab chemotherapy and in the rituximab arms compared with the splenectomy arm (p < 0.001). The 5-year overall survival was 77% and the 5-year LSS of 93%. There were no differences in the 5-year LSS according to the treatment received (p = 0.68). The 5-year CEFS in the overall series was 45%, and there were significant differences between scores A and B (p = 0.036). There were no significant differences when comparing LSS and progression-free survival in patients treated with rituximab or rituximab chemotherapy at diagnosis or after observation. Our data support HPLLs/ABC score as a practical tool for the management of SMZL, observation as the best approach for patients in group A and rituximab as the best treatment for group B.


Assuntos
Leucemia Linfocítica Crônica de Células B , Linfoma de Zona Marginal Tipo Células B , Neoplasias Esplênicas , Humanos , Rituximab/uso terapêutico , Resultado do Tratamento , Estudos Prospectivos , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Neoplasias Esplênicas/tratamento farmacológico , Neoplasias Esplênicas/patologia , Esplenectomia/efeitos adversos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico
13.
Cell Tissue Res ; 391(3): 577-594, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36527485

RESUMO

Preferentially expressed antigen in melanoma (PRAME) is a cancer/testis antigen (CTA) that is predominantly expressed in normal male gonad tissues and a variety of tumors. PRAME proteins are present in the acrosome and sperm tail, but their role in sperm function is unknown. The objective of this study was to examine the function of the bovine Y-linked PRAME (PRAMEY) during spermatozoal capacitation, the acrosome reaction (AR), and fertilization. Freshly ejaculated spermatozoa were induced to capacitate and undergo AR in vitro. Western blotting results revealed a decrease in the PRAMEY protein in capacitated spermatozoa, and the release of the PRAMEY protein from the acrosome during the AR, suggesting its involvement in sperm capacitation and AR. IVF was performed using in vitro matured bovine oocytes and cauda epididymal spermatozoa either treated with PRAMEY antibody, rabbit IgG, or DPBS. Sperm-egg binding and early embryos were examined at 6 and 45 h post IVF, respectively. The number of spermatozoa that bound per oocyte was nearly two-fold greater in the PRAMEY antibody treatment group (34.4) when compared to both the rabbit IgG (17.6) and DPBS (18.1) controls (P < 0.01). Polyspermy rate in the antibody-treated group (18.9%) was three-fold greater than the rabbit IgG control (6.0%) (P < 0.01). The results indicate that PRAMEY may play a role in anti-polyspermy defense. This study thus provides the initial evidence for the involvement of the PRAME protein family in sperm function and fertilization.


Assuntos
Sêmen , Espermatozoides , Coelhos , Masculino , Animais , Bovinos , Espermatozoides/metabolismo , Fertilização in vitro , Acrossomo , Capacitação Espermática , Imunoglobulina G , Fertilização
14.
PLoS Biol ; 18(7): e3000745, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32667908

RESUMO

Mutations create genetic variation for other evolutionary forces to operate on and cause numerous genetic diseases. Nevertheless, how de novo mutations arise remains poorly understood. Progress in the area is hindered by the fact that error rates of conventional sequencing technologies (1 in 100 or 1,000 base pairs) are several orders of magnitude higher than de novo mutation rates (1 in 10,000,000 or 100,000,000 base pairs per generation). Moreover, previous analyses of germline de novo mutations examined pedigrees (and not germ cells) and thus were likely affected by selection. Here, we applied highly accurate duplex sequencing to detect low-frequency, de novo mutations in mitochondrial DNA (mtDNA) directly from oocytes and from somatic tissues (brain and muscle) of 36 mice from two independent pedigrees. We found mtDNA mutation frequencies 2- to 3-fold higher in 10-month-old than in 1-month-old mice, demonstrating mutation accumulation during the period of only 9 mo. Mutation frequencies and patterns differed between germline and somatic tissues and among mtDNA regions, suggestive of distinct mutagenesis mechanisms. Additionally, we discovered a more pronounced genetic drift of mitochondrial genetic variants in the germline of older versus younger mice, arguing for mtDNA turnover during oocyte meiotic arrest. Our study deciphered for the first time the intricacies of germline de novo mutagenesis using duplex sequencing directly in oocytes, which provided unprecedented resolution and minimized selection effects present in pedigree studies. Moreover, our work provides important information about the origins and accumulation of mutations with aging/maturation and has implications for delayed reproduction in modern human societies. Furthermore, the duplex sequencing method we optimized for single cells opens avenues for investigating low-frequency mutations in other studies.


Assuntos
Envelhecimento/genética , Mamíferos/genética , Mitocôndrias/genética , Mutação/genética , Oócitos/metabolismo , Especificidade de Órgãos/genética , Animais , Análise Mutacional de DNA , DNA Mitocondrial/genética , Feminino , Frequência do Gene/genética , Deriva Genética , Células Germinativas/metabolismo , Padrões de Herança/genética , Modelos Logísticos , Masculino , Camundongos , Modelos Genéticos , Taxa de Mutação , Nucleotídeos/genética , Linhagem
15.
Arch Virol ; 168(8): 218, 2023 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-37530901

RESUMO

The human immunodeficiency virus type 1 (HIV-1) reservoir, composed of cells harboring the latent, integrated virus, is not eliminated by antiretroviral therapy. It therefore represents a significant barrier to curing the infection. The biology of HIV-1 reservoirs, the mechanisms of their persistence, and effective strategies for their eradication are not entirely understood. Here, we review the molecular mechanisms by which HIV-1 reservoirs develop, the cells and compartments where the latent virus resides, and advancements in curative therapeutic strategies. We first introduce statistics and relevant data on HIV-1 infection, aspects of pathogenesis, the role of antiretroviral therapy, and the general features of the latent HIV reservoir. Then, the article is built on three main pillars: The molecular mechanisms related to latency, the different strategies for targeting the reservoir to obtain a cure, and the current progress in immunotherapy to counteract said reservoirs.


Assuntos
Infecções por HIV , HIV-1 , Humanos , HIV-1/genética , Infecções por HIV/tratamento farmacológico , Latência Viral , Linfócitos T CD4-Positivos , Replicação Viral
16.
Surg Endosc ; 37(7): 5190-5195, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36947228

RESUMO

BACKGROUND: Increased complication rates following laparoscopic cholecystectomies have been described, likely related to surgical difficulty, anatomical variations, and gallbladder inflammation severity. Parkland Grading Scale (PGS) stratifies the severity of intraoperative findings to predict operative difficulty and complications. This study aims to validate PGS as a postoperative-outcome predictive tool, comparing its performance with Tokyo Guidelines Grading System (TGGS). METHODS: This is a single-center retrospective cohort study where PGS and TGGS performances were evaluated regarding intraoperative and postoperative outcomes. Both univariate and bivariate analyses were performed on each severity grading scale using STATA-SE 16.0 software. Additionally, we proposed a Logistic Regression Model for each scale. Their association with outcomes was compared between both scales by their Receiver Operating Characteristic Curve. RESULTS: 400 Patients were included. Grade 1 predominance was observed for both PGS and TGGS (47.36% and 25.3%, respectively). A positive association was observed between higher PGS grades and inpatient postoperative care, length of stay, ICU care, and antibiotic requirement. Based on the area under the ROC curve, better performance was observed for PGS over TGGS in the evaluated outcomes. CONCLUSION: PGS performed better than TGGS as a predictive tool for inpatient postoperative care, length of stay, ICU, and antibiotic requirement, especially in severe cases.


Assuntos
Colecistectomia Laparoscópica , Colecistite Aguda , Colecistite , Humanos , Estudos Retrospectivos , Índice de Gravidade de Doença , Colecistite/cirurgia , Tempo de Internação , Antibacterianos , Colecistite Aguda/cirurgia
17.
BMC Geriatr ; 23(1): 736, 2023 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-37957601

RESUMO

BACKGROUND: Older adults with cognitive impairment (CI) have higher multimorbidity and frailty prevalence, lower functional status and an increased likelihood to develop dementia, non-cognitive deficits, and adverse health-related events. +AGIL, a real-world program for frail older adults in a primary care area of Barcelona, is a pragmatic, multi-component and integrated intervention implemented since 2016. It includes physical activity, nutrition, sleep hygiene, revision and adequacy of pharmacological treatment, detection of undesired loneliness and screening for CI; to improve physical function in community-dwelling older adults. We aimed to assess the + AGIL longitudinal impact on physical function among community-dwelling frail older persons with CI. METHODS: An interventional cohort study included data from all the + AGIL consecutive participants from July 2016 until March 2020. Based on the comprehensive geriatric assessment, participants were offered a tailored multi-component community intervention, including a 10-week physical activity program led by an expert physical therapist. Physical performance was measured at baseline, three and six months follow-up. The pre-post impact on physical function was assessed by paired sample t-test for repeated samples. Linear mixed models were applied to analyze the + AGIL longitudinal impact. P-values < 0.05 were considered statistically significant. RESULTS: 194 participants were included (82 with CI, based on previous diagnosis or the Mini-COG screening tool), 68% women, mean age 81.6 (SD = 5.8) yo. Participants were mostly independent in Activities of Daily Living (mean Barthel = 92.4, SD = 11.1). The physical activity program showed high adherence (87.6% attended ≥ 75% sessions). At three months, there was a clinically and statistically significant improvement in the Short Physical Performance Battery (SPPB) and its subcomponents in the whole sample and after stratification for CI [CI group improvements: SPPB = 1.1 (SD = 1.8) points, gait speed (GS) = 0.05 (SD = 0.13) m/s, Chair stand test (CST)=-2.6 (SD = 11.4) s. Non-CI group improvements: SPPB = 1.6 (SD = 1.8) points, GS = 0.08 (SD = 0.13) m/s, CST=-6.4 (SD = 12.1) seg]. SPPB and gait speed remained stable at six months in the study sample and subgroups. CI had no significant impact on SPPB or GS improvements. CONCLUSION: Our results suggest that older adults with CI can benefit from a multidisciplinary integrated and comprehensive geriatric intervention to improve physical function, a component of frailty.


Assuntos
Disfunção Cognitiva , Fragilidade , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Masculino , Fragilidade/terapia , Estudos de Coortes , Vida Independente , Atividades Cotidianas , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/terapia
18.
Int J Audiol ; 62(2): 172-181, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35130459

RESUMO

OBJECTIVE: The auditory nerve overlapped waveform response (ANOW), a new measure that can be recorded non-invasively from humans, holds promise for providing more accurate assessment of low frequency hearing thresholds than currently used objective measures. This research aims to investigate the robustness and the nature of the ANOW response in humans. DESIGN: Repeated within-session recordings of the ANOW response using low-frequency Tone Bursts (TBs) were obtained at multiple stimulus levels. ANOW's absolute amplitude and phase locking value (PLV) measures were analysed to obtain normative data and to test the reliability of the ANOW response. STUDY SAMPLE: Thirteen normal hearing adults within the age range of 25 to 40 years. RESULTS: ANOW response was obtained to both 250 Hz and 500 Hz TBs and was traced down to 30-40 dB nHL. ANOW response showed significantly higher amplitude and stronger phase locking using 250 Hz TB compared to 500 Hz TB. High degree of test retest reliability of the ANOW response was found using 250 Hz TB at presentation levels higher than 40 dB nHL. CONCLUSIONS: ANOW response is recordable noninvasively using low-frequency TBs and shows higher robustness as the stimulus frequency decreases.


Assuntos
Audiometria de Resposta Evocada , Audição , Humanos , Adulto , Estimulação Acústica , Reprodutibilidade dos Testes , Limiar Auditivo/fisiologia , Audição/fisiologia , Nervo Coclear , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia
19.
Vet Radiol Ultrasound ; 64(5): 834-843, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37496364

RESUMO

Arterial enhancement is the commonly described characteristic of canine insulinomas in contrast-enhanced computed tomography (CECT). However, this finding is also reported as inconsistent. The main aim of this single-center retrospective observational study was to describe the contrast enhancement (CE) pattern of canine presumed and confirmed insulinomas and presumed metastases in three consecutive (early, mid, and late) arterial phases. Included dogs had a medical-record-based clinical or cytological/histopathological diagnosis of insulinoma and quadruple-phase CECT. The arterial phases were identified according to published literature. The arterial enhancement of confirmed and presumed lesions was assessed using a visual grading score. Twelve dogs with a total of 17 pancreatic nodules were analyzed. Three dogs had multiple pancreatic nodules and nine had solitary findings. Four insulinomas were histopathologically confirmed. Late arterial phase (LAP) images demonstrated the largest number of pancreatic nodules reaching the highest enhancement scores (n = 13, 76%). All analyzed dogs had CT evidence of arterially enhancing nodules in the liver (n = 12), seven in the hepatic, splenic, or colic lymph nodes, and three in the spleen. Three out of five sampled livers and three lymph nodes were metastatic. All sampled spleens were benign. Avid arterial enhancement was the most dominant feature of canine presumed and confirmed insulinomas and presumed metastases in quadruple-phase CECT. The highest enhancement scores were observed primarily in LAP, followed by MAP. Authors, therefore, recommend including LAP in the standard CT protocol for dogs with suspected pancreatic insulinomas.


Assuntos
Insulinoma , Neoplasias Pancreáticas , Animais , Cães , Abdome , Insulinoma/diagnóstico por imagem , Insulinoma/veterinária , Fígado/patologia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/veterinária , Tomografia Computadorizada por Raios X/veterinária , Tomografia Computadorizada por Raios X/métodos
20.
Rev Esp Enferm Dig ; 115(9): 537-538, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37539589

RESUMO

We present a case of a 40-year-old woman with double-lung transplant with extracorporeal circulation (EC) due to pulmonary hypertension (pulmonary veno-occlusive disease form (PVOD)) secondary to mixed connective tissue disease (MCTD). On day 6 postoperatively, abdominal pain and distension was noticed, since abdominal CT scan was performed, showing emphysematous gastritis with gastric wall ischemia and peritonitis. Therefore, emergent surgery was proposed. By open surgery approach, a total gastrectomy with Roux-en-Y and esophagojejunal anastomosis was performed. On day 6 after gastrectomy, intraluminal bleeding of the esophagojejunal anastomosis was detected in control CT, which was not need any aggressive treatment. Postoperative evolution was favourable, being discharged from the intensive care unit on the day 34 and from the hospital two months later.


Assuntos
Laparoscopia , Transplante de Pulmão , Neoplasias Gástricas , Feminino , Humanos , Adulto , Estômago , Gastrectomia , Anastomose em-Y de Roux , Prognóstico , Neoplasias Gástricas/cirurgia , Transplante de Pulmão/efeitos adversos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA