349 results on '"Rafael Oliva"'
Search Results
2. Effects of once-weekly subcutaneous retatrutide on weight and metabolic markers: A systematic review and meta-analysis of randomized controlled trials
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Eric Pasqualotto, Rafael Oliva Morgado Ferreira, Matheus Pedrotti Chavez, Alexandre Hohl, Marcelo Fernando Ronsoni, Tales Pasqualotto, Francisco Cezar Aquino de Moraes, Larissa Hespanhol, Janine Midori Figueiredo Watanabe, Carine Lütkemeyer, and Simone van de Sande-Lee
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Retatrutide ,Body weight ,Obesity ,Metabolism ,Physiology ,QP1-981 ,Biochemistry ,QD415-436 - Abstract
Aim: To assess the effects of once-weekly subcutaneous retatrutide on weight and metabolic markers and the occurrence of side effects in patients with overweight, obesity and/or type 2 diabetes (T2D). Methods: PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were systematically searched for placebo-controlled, randomized clinical trials (RCTs) published up until February 23, 2024. Weighted mean differences (WMDs) for continuous outcomes and risk ratios (RRs) for binary endpoints were computed, with 95 % confidence intervals (CIs). Results: A total of three studies were included, comprising 640 patients, of whom 510 were prescribed retatrutide. Compared with placebo, retatrutide significantly reduced body weight (WMD -10.66 kg; 95 % CI -17.63, −3.69), body mass index (WMD -4.53 kg/m2; 95 % CI -7.51, −1.55), and waist circumference (WMD -6.61 cm; 95 % CI -13.17, −0.05). In addition, retatrutide significantly increased the proportion of patients who achieved a weight reduction of ≥5 % (RR 2.92; 95 % CI 2.17–3.93), ≥10 % (RR 9.32; 95 % CI 4.56–19.06), ≥15 % (RR 18.40; 95 % CI 6.00–56.42), and ≥20 % (RR 16.61; 95 % CI 4.17–66.12). Conclusions: In this meta-analysis, the use of once-weekly subcutaneous retatrutide was associated with a significant reduction in body weight and improvement of metabolic markers in patients with overweight, obesity and/or T2D, compared with placebo, with an increase in non-severe gastrointestinal and hypersensitivity adverse events. Phase 3 RCTs are expected to shed further light on the efficacy and safety of once-weekly subcutaneous retatrutide over the long term.
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- 2024
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3. Anticoagulantes Orais Diretos versus Antagonistas da Vitamina K para Trombo Ventricular Esquerdo: Uma Metanálise com Análise Sequencial de Ensaios
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Eric Pasqualotto, Douglas Mesadri Gewehr, Rafael Oliva Morgado Ferreira, Matheus Pedrotti Chavez, Caroliny Hellen Silva, Sara Almeida Cruz, Jhonny Limachi-Choque, Amanda Park, Mário Sérgio Soares de Azeredo Coutinho, and Luiz Fernando Kubrusly
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Varfarina ,Inibidores do Fator Xa ,Trombose ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Resumo Fundamento Os antagonistas da vitamina K (AVKs) são o tratamento de primeira linha recomendado para trombo ventricular esquerdo (TVE); entretanto, os anticoagulantes orais diretos (AODs) têm sido considerados uma terapia alternativa. Objetivos Avaliar a eficácia e a segurança dos AODs em comparação com a terapia com AVKs em pacientes com TVE. Métodos PubMed, Embase e Cochrane foram sistematicamente pesquisados em busca de ensaios clínicos randomizados ou estudos de coorte que comparassem AODs versus AVKs para TVE. As razões de risco (RR) foram calculadas para desfechos binários, com intervalos de confiança (IC) de 95%. A significância estatística foi definida como valor de p < 0,05. Resultados Foram incluídos um total de 4 ensaios clínicos randomizados e 29 estudos de coorte, com 4.450 pacientes designados para AODs ou AVKs. Não houve diferença significativa entre os grupos para acidente vascular cerebral ou eventos embólicos sistêmicos (AVC/EES) (RR 0,84; IC 95% 0,65 a 1,07; p = 0,157), acidente vascular cerebral (RR 0,73; IC 95% 0,48 a 1,11; p = 0,140), eventos embólicos sistêmicos (EES) (RR 0,69; IC 95% 0,40 a 1,17; p = 0,166), resolução do trombo (RR 1,05; IC 95% 0,99 a 1,11; p = 0,077), qualquer sangramento (RR 0,78; IC 95% 0,60 a 1,00; p = 0,054), sangramento clinicamente relevante (RR 0,69; IC 95% 0,46 a 1,03; p = 0,066), sangramento menor (RR 0,73; IC 95% 0,43 a 1,23; p = 0,234), sangramento maior (RR 0,87; IC 95% 0,42 a 1,80; p = 0,705) e mortalidade por todas as causas (RR 1,05; IC 95% 0,79 a 1,39; p = 0,752). Em comparação com AVKs, a rivaroxabana reduziu significativamente AVC/EES (RR 0,35; IC 95% 0,16 a 0,91; p = 0,029) e EES (RR 0,39; IC 95% 0,16 a 0,95; p = 0,037). Conclusões Os AODs tiveram uma taxa semelhante de eventos tromboembólicos e hemorrágicos, bem como de resolução do trombo, em comparação com os AVKs no tratamento de TVE. A terapia com rivaroxabana teve uma redução significativa nos eventos tromboembólicos, em comparação com os AVKs.
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- 2024
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4. Efficacy of the hybrid closed-loop insulin delivery system in children and adolescents with type 1 diabetes: a meta-analysis with trial sequential analysis
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Rafael Oliva Morgado Ferreira, Talita Trevisan, Eric Pasqualotto, Pedro Schmidt, Matheus Pedrotti Chavez, Janine Midori Figueiredo Watanabe, and Simone van de Sande-Lee
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Closed-loop ,glucose control ,diabetes technology ,type 1 diabetes, meta-analysis ,Medicine ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
ABSTRACT The aim of this study was to assess the efficacy and safety of hybrid closed-loop (HCL) systems for insulin delivery in children and adolescents with type 1 diabetes (T1D). We searched Embase, PubMed, and Cochrane Library for randomized controlled trials (RCTs) published until March 2023 comparing the HCL therapy with control therapies for children and adolescents with T1D. We computed weighted mean differences (WMDs) for continuous outcomes and risk ratios (RRs) with 95% confidence intervals (CIs) for binary endpoints. Four RCTs and 501 patients were included, of whom 323 were randomized to HCL therapy. Compared with control therapies, HCL significantly improved the period during which glucose level was 70-180 mg/dL (WMD 10.89%, 95% CI 8.22-13.56%) and the number of participants with glycated hemoglobin (HbA1c) level < 7% (RR 2.61, 95% CI 1.29-5.28). Also, HCL significantly reduced the time during which glucose level was > 180 mg/dL (WMD -10.46%, 95% CI -13.99 to -6.93%) and the mean levels of glucose (WMD -16.67 mg/dL, 95% CI -22.25 to -11.09 mg/dL) and HbA1c (WMD -0.50%, 95% CI -0.68 to -0.31). There were no significant differences between therapies regarding time during which glucose level was < 70 mg/dL or
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- 2024
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5. Long-term impact of home-based monitoring after an admission for acute decompensated heart failure: a systematic review and meta-analysis of randomised controlled trialsResearch in context
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Mariana R.C. Clemente, Nicole Felix, Denilsa D.P. Navalha, Eric Pasqualotto, Rafael Oliva Morgado Ferreira, Marcelo A.P. Braga, Alleh Nogueira, Thomaz Alexandre Costa, Alice D. Marinho, and Amanda Fernandes
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Home-based monitoring ,Remote monitoring ,Heart failure ,Acute decompensated heart failure ,Medicine (General) ,R5-920 - Abstract
Summary: Background: Patients with heart failure have high rehospitalisation rates and poor cardiovascular outcomes. Home-based monitoring (HBM) has emerged with promising results in different settings. However, its long-term effects on patients recently admitted for acute decompensated heart failure (ADHF) remain uncertain. Methods: We systematically searched PubMed, Embase, and Cochrane Library for randomised controlled trials (RCTs) comparing HBM with usual care (UC) that were published between database inception and June 24, 2023. We included studies with patients admitted for ADHF in the previous 6 months and with a minimum follow-up of 6 months. We excluded studies with patients hospitalised for reasons other than ADHF and studies with disproportional education interventions between arms. Statistical analyses were performed using R software version 4.3.2. We pooled risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI) for categorical and continuous outcomes, respectively. Cochrane Collaboration’s tool for assessing risk of bias in RCTs (RoB 2) was used to assess study quality. Publication bias was assessed via funnel plots and Egger’s test, and heterogeneity was assessed through I2 statistics and sensitivity analysis. The protocol for this systematic review and meta-analysis was registered in the International Prospective Register of Systematic Reviews (PROSPERO, CRD42023465359). Findings: We included 16 RCTs comprising 4629 patients, of whom 2393 (51.7%) were randomised to HBM and 3150 (68%) were men. Follow-up ranged from six to fifteen months. As compared with UC, HBM significantly reduced all-cause mortality (RR 0.75; 95% CI 0.61, 0.91; p = 0.005), all-cause hospitalisations (RR 0.82; 95% CI 0.70, 0.97; p = 0.018), cardiovascular (CV) mortality (RR 0.53; 95% CI 0.36, 0.79; p = 0.002), hospitalisations for heart failure (RR 0.75; 95% CI 0.62, 0.91; p = 0.004), and CV hospitalisations (RR 0.72; 95% CI 0.55, 0.95; p = 0.018). There were no significant differences in length of hospital stay (MD 0.97 days; 95% CI -0.90, 2.84; p = 0.308). Interpretation: In patients recently admitted with ADHF, HBM significantly reduces long-term all-cause mortality and hospitalisations, CV mortality and hospitalisations, and hospitalisations for heart failure, as compared with UC. This supports the implementation of HBM as a standard practice to optimise patient outcomes following admissions for ADHF. However, future studies are warranted to evaluate the efficacy and safety of implementing HBM in the real-world setting. Funding: None.
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- 2024
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6. PD-1/PD-L1 Inhibitors plus Chemotherapy Versus Chemotherapy Alone for Resectable Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
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Eric Pasqualotto, Francisco Cezar Aquino de Moraes, Matheus Pedrotti Chavez, Maria Eduarda Cavalcanti Souza, Anna Luíza Soares de Oliveira Rodrigues, Rafael Oliva Morgado Ferreira, Lucca Moreira Lopes, Artur Menegaz de Almeida, Marianne Rodrigues Fernandes, and Ney Pereira Carneiro dos Santos
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immune checkpoint inhibitors ,neoadjuvant therapy ,lung cancer ,immunotherapy ,early stage ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background: The benefit of adding programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors to the treatment of early-stage non-small cell lung cancer (NSCLC), both neoadjuvant therapy (NAT) and adjuvant therapy (AT), is not yet fully elucidated. Methods: We searched PubMed, Embase, and Cochrane databases for randomized controlled trials (RCT) that investigated PD-1/PD-L1 inhibitors plus chemotherapy for resectable stage NSCLC. We computed hazard ratios (HRs) or odds ratios (ORs) for binary endpoints, with 95% confidence intervals (CIs). Results: A total of seven RCTs comprising 3915 patients with resectable stage NSCLC were randomized to chemotherapy with or without PD-1/PD-L1 inhibitors as NAT or AT. As NAT, the PD-1/PD-L1 inhibitors plus chemotherapy group demonstrated significantly improved overall survival (HR 0.66; 95% CI 0.51–0.86) and event-free survival (HR 0.53; 95% CI 0.43–0.67) compared with the chemotherapy alone group. There was a significant increase in favor of the PD-1/PD-L1 inhibitors plus chemotherapy group for major pathological response (OR 6.40; 95% CI 3.86–10.61) and pathological complete response (OR 8.82; 95% CI 4.51–17.26). Meanwhile, as AT, disease-free survival was significant in favor of the PD-1/PD-L1 inhibitors plus chemotherapy group (HR 0.78; 95% CI 0.69–0.90). Conclusions: In this comprehensive systematic review and meta-analysis of RCTs, the incorporation of PD-1/PD-L1 inhibitors alongside chemotherapy offers a promising prospect for reshaping the established treatment paradigms for patients diagnosed with resectable stages of NSCLC. Moreover, our analyses support that neoadjuvant administration with these agents should be encouraged, in light of the fact that it was associated with an increased survival and pathological response, at the expense of a manageable safety profile.
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- 2023
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7. Development and evolution of OES system, datalogger equipment and associated software
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Pablo Bertinat, Juan Salerno, Marcelo Castello, and Rafael Oliva
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datalogger ,energia eolica ,mediciones ,software ,Electrical engineering. Electronics. Nuclear engineering ,TK1-9971 ,Computer engineering. Computer hardware ,TK7885-7895 - Abstract
This paper delineates the different stages in the design and evolution of a datalogger system and its associated software. It was developed within the framework of a Project aimed at the study and processing of wind data for power generation, and carried out with open source tools. This project has focused on the development of in-house technology, with capabilities and performance comparable to equipment available on the market. Commercial off-the-shelf systems have been analysed, as well as associated software in order to set the general features and requirements for the prototype. An important number of industry-standard features in the processing of wind data for electric power generation have been considered. Hardware was developed and a web-based system located in an in-house server have been deployed, both of which work together to fulfill the proposed functions.
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- 2021
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8. The Role of Testosterone in Spermatogenesis: Lessons From Proteome Profiling of Human Spermatozoa in Testosterone Deficiency
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Giuseppe Grande, Ferran Barrachina, Ada Soler-Ventura, Meritxell Jodar, Francesca Mancini, Riccardo Marana, Sabrina Chiloiro, Alfredo Pontecorvi, Rafael Oliva, and Domenico Milardi
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sperm ,hypogonadism ,proteomics ,LH deficiency ,testosterone ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Testosterone is essential to maintain qualitative spermatogenesis. Nonetheless, no studies have been yet performed in humans to analyze the testosterone-mediated expression of sperm proteins and their importance in reproduction. Thus, this study aimed to identify sperm protein alterations in male hypogonadism using proteomic profiling. We have performed a comparative proteomic analysis comparing sperm from fertile controls (a pool of 5 normogonadic normozoospermic fertile men) versus sperm from patients with secondary hypogonadism (a pool of 5 oligozoospermic hypogonadic patients due to isolated LH deficiency). Sperm protein composition was analyzed, after peptide labelling with Isobaric Tags, via liquid chromatography followed by tandem mass spectrometry (LC-MS/MS) on an LTQ Velos-Orbitrap mass spectrometer. LC-MS/MS data were analyzed using Proteome Discoverer. Criteria used to accept protein identification included a false discovery rate (FDR) of 1% and at least 1 peptide match per protein. Up to 986 proteins were identified and, of those, 43 proteins were differentially expressed: 32 proteins were under-expressed and 11 were over-expressed in the pool of hypogonadic patients compared to the controls. Bioinformatic analyses were performed using UniProt Knowledgebase, and the Gene Ontology Consortium database based on PANTHER. Notably, 13 of these 43 differentially expressed proteins have been previously reported to be related to sperm function and spermatogenesis. Western blot analyses for A-Kinase Anchoring Protein 3 (AKAP3) and the Prolactin Inducible Protein (PIP) were used to confirm the proteomics data. In summary, a high-resolution mass spectrometry-based proteomic approach was used for the first time to describe alterations of the sperm proteome in secondary male hypogonadism. Some of the differential sperm proteins described in this study, which include Prosaposin, SMOC-1, SERPINA5, SPANXB1, GSG1, ELSPBP1, fibronectin, 5-oxoprolinase, AKAP3, AKAP4, HYDIN, ROPN1B, ß-Microseminoprotein and Protein S100-A8, could represent new targets for the design of infertility treatments due to androgen deficiency.
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- 2022
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9. H4K5 Butyrylation Coexist with Acetylation during Human Spermiogenesis and Are Retained in the Mature Sperm Chromatin
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Alberto de la Iglesia, Paula Jauregi, Meritxell Jodar, Ferran Barrachina, Lukas Ded, Carme Mallofré, Leonardo Rodríguez-Carunchio, Juan Manuel Corral, Josep Lluís Ballescà, Katerina Komrskova, Judit Castillo, and Rafael Oliva
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butyrylation ,acetylation ,H4K5 ,spermatogenesis ,sperm ,sperm chromatin ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Male germ cells experience a drastic chromatin remodeling through the nucleo-histone to nucleo-protamine (NH-NP) transition necessary for proper sperm functionality. Post-translational modifications (PTMs) of H4 Lys5, such as acetylation (H4K5ac), play a crucial role in epigenetic control of nucleosome disassembly facilitating protamine incorporation into paternal DNA. It has been shown that butyrylation on the same residue (H4K5bu) participates in temporal regulation of NH-NP transition in mice, delaying the bromodomain testis specific protein (BRDT)-dependent nucleosome disassembly and potentially marking retained nucleosomes. However, no information was available so far on this modification in human sperm. Here, we report a dual behavior of H4K5bu and H4K5ac in human normal spermatogenesis, suggesting a specific role of H4K5bu during spermatid elongation, coexisting with H4K5ac although with different starting points. This pattern is stable under different testicular pathologies, suggesting a highly conserved function of these modifications. Despite a drastic decrease of both PTMs in condensed spermatids, they are retained in ejaculated sperm, with 30% of non-colocalizing nucleosome clusters, which could reflect differential paternal genome retention. Whereas no apparent effect of these PTMs was observed associated with sperm quality, their presence in mature sperm could entail a potential role in the zygote.
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- 2022
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10. Novel P397S MAPT variant associated with late onset and slow progressive frontotemporal dementia
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Sergi Borrego‐Écija, Anna Antonell, Joan Anton Puig‐Butillé, Inmaculada Pericot, Carme Prat‐Bravo, Maria Teresa Abellan‐Vidal, Javier Mallada, Jaume Olives, Neus Falgàs, Rafael Oliva, Albert Lladó, and Raquel Sánchez‐Valle
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Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Mutations in the MAPT gene cause frontotemporal dementia with tau deposits. We report the novel p.P397S MAPT variant in eight subjects from five apparently nonrelated families suffering from frontotemporal dementia with autosomal dominant pattern of inheritance. In silico analysis reported conflicting evidence of pathogenicity. The segregation analysis support that this variant is likely pathogenic. The mean age at onset (61.4 years) and mean disease duration (13.9 years) of these subjects and their affected relatives were significantly higher compared with our series of p.P301L MAPT mutation carriers. These findings suggest that p.P397S variant could be a new MAPT mutation associated with a less aggressive phenotype than other MAPT mutations.
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- 2019
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11. 'In vitro' Effect of Different Follicle—Stimulating Hormone Preparations on Sertoli Cells: Toward a Personalized Treatment for Male Infertility
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Iva Arato, Giuseppe Grande, Ferran Barrachina, Catia Bellucci, Cinzia Lilli, Meritxell Jodar, Maria Chiara Aglietti, Francesca Mancini, Federica Vincenzoni, Alfredo Pontecorvi, Riccardo Calafiore, Rafael Oliva, Giovanni Luca, Francesca Mancuso, and Domenico Milardi
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Sertoli cells ,alpha follitropin ,beta follitropin ,urofollitropin ,proteomic analysis ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Follicle-stimulating hormone (FSH), a major regulator of spermatogenesis, has a crucial function in the development and function of the testis and it is extensively given as a fertility treatment to stimulate spermatogenesis. We analyzed the effects of different FSH preparations (α-follitropin, β-follitropin, and urofollitropin) in combination with testosterone on porcine pre-pubertal Sertoli cells. To study the effect of the different FSH treatments in the Sertoli cell function we performed Real Time PCR analysis of AMH, inhibin B, and FSH-r, an ELISA assay for AMH and inhibin B, and a high-throughput comparative proteomic analysis. We verified that all three preparations induced a reduction of AMH in terms of mRNA and secreted proteins, and an increase of inhibin B in terms of mRNA in all the FSH formulations, while solely α-follitropin produced an increase of secreted inhibin B in the culture medium. Comparative proteomic analysis of the three FSH preparations identified 46 proteins, 11 up-regulated and 2 down-regulated. Surprisingly, the combination of testosterone with β-follitropin specifically induced an up-regulation of eight specific secreted proteins. Our study, showing that the three different FSH preparations induce different effects, could offer the opportunity to shed light inside new applications to a personalized reproductive medicine.
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- 2020
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12. Proteomic Changes in Human Sperm During Sequential in vitro Capacitation and Acrosome Reaction
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Judit Castillo, Orleigh Adeleccia Bogle, Meritxell Jodar, Forough Torabi, David Delgado-Dueñas, Josep Maria Estanyol, Josep Lluís Ballescà, David Miller, and Rafael Oliva
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sperm ,spermatozoa ,capacitation ,acrosome reaction ,proteomics ,mass spectrometry ,Biology (General) ,QH301-705.5 - Abstract
The male gamete is not completely mature after ejaculation and requires further events in the female genital tract to acquire fertilizing ability, including the processes of capacitation and acrosome reaction. In order to shed light on protein changes experienced by the sperm cell in preparation for fertilization, a comprehensive quantitative proteomic profiling based on isotopic peptide labeling and liquid chromatography followed by tandem mass spectrometry was performed on spermatozoa from three donors of proven fertility under three sequential conditions: purification with density gradient centrifugation, incubation with capacitation medium, and induction of acrosome reaction by exposure to the calcium ionophore A23187. After applying strict selection criteria for peptide quantification and for statistical analyses, 36 proteins with significant changes in their relative abundance within sperm protein extracts were detected. Moreover, the presence of peptide residues potentially harboring sites for post-translational modification was revealed, suggesting that protein modification may be an important mechanism in sperm maturation. In this regard, increased levels of proteins mainly involved in motility and signaling, both regulated by protein modifiers, were detected in sperm lysates following incubation with capacitation medium. In contrast, less abundant proteins in acrosome-reacted cell lysates did not contain potentially modifiable residues, suggesting the possibility that all those proteins might be relocated or released during the process. Protein-protein interaction analysis revealed a subset of proteins potentially involved in sperm maturation, including the proteins Erlin-2 (ERLIN2), Gamma-glutamyl hydrolase (GGH) and Transmembrane emp24 domain-containing protein 10 (TMED10). These results contribute to the current knowledge of the molecular basis of human fertilization. It should now be possible to further validate the potential role of the detected altered proteins as modulators of male infertility.
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- 2019
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13. Protamine Characterization by Top-Down Proteomics: Boosting Proteoform Identification with DBSCAN
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Gianluca Arauz-Garofalo, Meritxell Jodar, Mar Vilanova, Alberto de la Iglesia Rodriguez, Judit Castillo, Ada Soler-Ventura, Rafael Oliva, Marta Vilaseca, and Marina Gay
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male infertility ,sperm ,protamine ,LC-MS/MS ,top-down proteomics ,proteoform ,Microbiology ,QR1-502 - Abstract
Protamines replace histones as the main nuclear protein in the sperm cells of many species and play a crucial role in compacting the paternal genome. Human spermatozoa contain protamine 1 (P1) and the family of protamine 2 (P2) proteins. Alterations in protamine PTMs or the P1/P2 ratio may be associated with male infertility. Top-down proteomics enables large-scale analysis of intact proteoforms derived from alternative splicing, missense or nonsense genetic variants or PTMs. In contrast to current gold standard techniques, top-down proteomics permits a more in-depth analysis of protamine PTMs and proteoforms, thereby opening up new perspectives to unravel their impact on male fertility. We report on the analysis of two normozoospermic semen samples by top-down proteomics. We discuss the difficulties encountered with the data analysis and propose solutions as this step is one of the current bottlenecks in top-down proteomics with the bioinformatics tools currently available. Our strategy for the data analysis combines two software packages, ProSight PD (PS) and TopPIC suite (TP), with a clustering algorithm to decipher protamine proteoforms. We identified up to 32 protamine proteoforms at different levels of characterization. This in-depth analysis of the protamine proteoform landscape of normozoospermic individuals represents the first step towards the future study of sperm pathological conditions opening up the potential personalized diagnosis of male infertility.
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- 2021
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14. Direct oral anticoagulants versus vitamin K antagonists in patients with atrial fibrillation on chronic hemodialysis: a meta-analysis of randomized controlled trials
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Navalha, Denilsa D. P., Felix, Nicole, Nogueira, Alleh, Clemente, Mariana, Marinho, Alice D., Ferreira, Rafael Oliva Morgado, Pasqualotto, Eric, Dagostin, Caroline Serafim, Pinto, Luis Cláudio Santos, and Fernandes, Gilson C.
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- 2024
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15. Montaje, medición y seguimiento del funcionamiento de Paneles Fotovoltaicos en combinación a un sistema de generación eólico de baja potencia instalados en un invernadero
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Rafael Oliva, Jose Gonzalez, and Gustavo Fernando Cardenas
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energías alternativas ,sistemas híbridos ,sistemas fotovoltaicos ,paneles fotovoltaicos ,mediciones ,patagonia sur ,General Works - Abstract
Este Proyecto consiste en el monitoreo de un sistema de energía eólica de baja potencia combinado con paneles fotovoltaicos que se encuentran acoplados a un invernáculo con el fin de suministrar energía eléctrica para las funciones de iluminación y control del mismo. La intención es mejorar la experiencia del Grupo de Energías Alternativas de la Universidad en registro, procesamiento y elaboración de informes sobre producción de equipos de ésta índole en la región, como así también en la medición de recursos de energía renovable y preparación de redes de instrumental para implementar organizadamente las mediciones y procesamiento de los resultados.
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- 2016
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16. Human sperm chromatin epigenetic potential: genomics, proteomics, and male infertility
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Judit Castillo, Josep Maria Estanyol, Josep Lluis Ballescà, and Rafael Oliva
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gene regulation ,Musashi ,Musashi-1 ,Musashi-2 ,posttranscriptional control ,RNA binding proteins ,spermatogenesis ,splicing ,testis ,translation ,cell fate ,cell stress ,importin ,karyopherin ,nucleocytoplasmic transport ,spermatid ,spermatocyte ,artificial insemination ,biomarker ,fertility ,fertilization ,flow cytometry ,infertility ,nanotechnology ,oocyte activation ,Postacrosomal Sheath WWI Domain Binding Protein ,sperm ,SPTRX3 ,thioredoxin ,ubiquitin ,ATP binding cassette transporters ,albumin ,high-density lipoprotein ,lipid rafts ,membrane fluidity ,membrane microdomains ,membrane packing ,oxysterols ,reverse cholesterol transport ,sterol transporters ,egg ,heat shock protein A2 ,molecular chaperone ,sperm-egg interactions ,dehydrogenases ,oxidases ,peroxiredoxins ,reactive oxygen species ,spermatozoa ,thiols ,thioredoxins ,antigen-presenting cells ,autoimmunity ,dendritic cells ,epididymis ,macrophages ,peripheral tolerance ,sperm maturation ,genomics ,male infertility ,proteomics ,sperm chromatin ,sperm epigenetics ,Diseases of the genitourinary system. Urology ,RC870-923 - Abstract
The classical idea about the function of the mammalian sperm chromatin is that it serves to transmit a highly protected and transcriptionally inactive paternal genome, largely condensed by protamines, to the next generation. In addition, recent sperm chromatin genome-wide dissection studies indicate the presence of a differential distribution of the genes and repetitive sequences in the protamine-condensed and histone-condensed sperm chromatin domains, which could be potentially involved in regulatory roles after fertilization. Interestingly, recent proteomic studies have shown that sperm chromatin contains many additional proteins, in addition to the abundant histones and protamines, with specific modifications and chromatin affinity features which are also delivered to the oocyte. Both gene and protein signatures seem to be altered in infertile patients and, as such, are consistent with the potential involvement of the sperm chromatin landscape in early embryo development. This present work reviews the available information on the composition of the human sperm chromatin and its epigenetic potential, with a particular focus on recent results derived from high-throughput genomic and proteomic studies. As a complement, we provide experimental evidence for the detection of phosphorylations and acetylations in human protamine 1 using a mass spectrometry approach. The available data indicate that the sperm chromatin is much more complex than what it was previously thought, raising the possibility that it could also serve to transmit crucial paternal epigenetic information to the embryo.
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- 2015
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17. Efficacy and safety of Zolbetuximab plus chemotherapy for advanced CLDN18.2-positive gastric or gastro-oesophageal adenocarcinoma: a meta-analysis of randomized clinical trials
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de Moraes, Francisco Cezar Aquino, Pasqualotto, Eric, Chavez, Matheus Pedrotti, Ferreira, Rafael Oliva Morgado, De Castria, Tiago Biachi, and Burbano, Rommel Mario Rodríguez
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- 2024
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18. Surgical versus non-surgical treatment of flail chest: a meta-analysis of randomized controlled trials
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Ferreira, Rafael Oliva Morgado, Pasqualotto, Eric, Viana, Patrícia, Schmidt, Pedro Henrique Siedschlag, Andrighetti, Leonardo, Chavez, Matheus Pedrotti, Flausino, Felippe, and de Oliveira Filho, Getúlio Rodrigues
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- 2023
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19. Delegação e controle político das agências reguladoras no Brasil Delegation and political control of the regulatory agencies in Brazil
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Fernanda Meirelles and Rafael Oliva
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agência reguladora ,regulação ,controle político ,delegação ,accountability ,regulatory agency ,regulation ,political control ,delegation ,Political institutions and public administration (General) ,JF20-2112 - Abstract
A partir de um esforço de sistematização dos mecanismos de controle político previstos no modelo institucional originalmente concebido para as agências reguladoras, este artigo avalia os mecanismos de controle político presentes no arcabouço institucional das agências reguladoras independentes (ARIs) brasileiras e analisa as alterações relacionadas ao controle político introduzidas pelo projeto de lei encaminhado pelo governo ao Congresso em 12 de abril de 2004. Após contextualizar o debate sobre o controle político das ARIs no Brasil, o artigo discute as relações entre delegação e responsabilização. Em seguida, na busca de um parâmetro para avaliar o modelo brasileiro de agências reguladoras (ARs), identifica os instrumentos de controle político utilizados na experiência americana. Finalmente, avalia a realidade institucional atual das ARIs brasileiras e comenta as contribuições do recente projeto de lei em relação ao controle político das agências.This article systematizes the political control mechanisms provided by the institutional model originally conceived for the regulatory agencies in order to assess the political control mechanisms in the institutional framework of the Brazilian independent regulatory agencies (IRAs) and analyze the political control changes introduced by the law proposed by the government to Congress in April 12, 2004. After putting into context the debate on political control over the Brazilian IRAs, the article discusses the relationship between delegation and accountability. Then, so as to find a parameter for assessing the Brazilian regulatory agency model, it identifies the political control mechanisms used by the American experience. Finally, it assesses the current institutional situation of the Brazilian IRAs and comments on the contribution of the recent law proposal in relation to agency political control.
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- 2006
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20. Catheter ablation for atrial fibrillation in heart failure with reduced ejection fraction patients: A meta-analysis
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Pasqualotto, Eric, Ternes, Caique M.P., Chavez, Matheus Pedrotti, Polanczyk, Carisi A., Ferreira, Rafael Oliva Morgado, Nienkötter, Thiago, Oliveira Almeida, Gustavo de, Bertoli, Edmundo, Clemente, Mariana R.C., d'Avila, Andre, and Rohde, Luis E.
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- 2024
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21. The effect of sodium-glucose transporter 2 inhibitors on stroke in patients with type 2 diabetes: A meta-analysis
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Pasqualotto, Eric, Rodrigues, Farley Reis, e Silva Ribeiro, Giovana Barros, de Oliveira Almeida, Gustavo, Kabariti, Júlia Camargo, Ferreira, Rafael Oliva Morgado, Chavez, Matheus Pedrotti, Clemente, Mariana R.C., Sur, Nicole B., and Di Luca, Daniel G.
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- 2024
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22. Effects of once-weekly subcutaneous retatrutide on weight and metabolic markers: A systematic review and meta-analysis of randomized controlled trials
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Pasqualotto, Eric, Ferreira, Rafael Oliva Morgado, Chavez, Matheus Pedrotti, Hohl, Alexandre, Ronsoni, Marcelo Fernando, Pasqualotto, Tales, Moraes, Francisco Cezar Aquino de, Hespanhol, Larissa, Figueiredo Watanabe, Janine Midori, Lütkemeyer, Carine, and van de Sande-Lee, Simone
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- 2024
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- View/download PDF
23. Intravascular imaging-guided vs. angiography-guided percutaneous coronary intervention: A systematic review and meta-analysis of randomized controlled trials in high-risk patients and complex coronary anatomies
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Teixeira, Larissa, Ferreira, Rafael Oliva Morgado, Navalha, Denilsa D.P., Pasqualotto, Eric, Fae, Isabela Galizzi, Gibicoski, Tathiane, Chavez, Matheus Pedrotti, Talavera, Armando, Athayde, Guilherme, and Chamie, Daniel
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- 2024
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24. Long-term impact of home-based monitoring after an admission for acute decompensated heart failure: a systematic review and meta-analysis of randomised controlled trials
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Clemente, Mariana R.C., Felix, Nicole, Navalha, Denilsa D.P., Pasqualotto, Eric, Morgado Ferreira, Rafael Oliva, Braga, Marcelo A.P., Nogueira, Alleh, Costa, Thomaz Alexandre, Marinho, Alice D., and Fernandes, Amanda
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- 2024
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25. Continuous Glucose Monitoring Systems in Noninsulin-Treated People with Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
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Ferreira, Rafael Oliva Morgado, primary, Trevisan, Talita, additional, Pasqualotto, Eric, additional, Chavez, Matheus Pedrotti, additional, Marques, Beatriz Friedrichsen, additional, Lamounier, Rodrigo Nunes, additional, and van de Sande-Lee, Simone, additional
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- 2024
- Full Text
- View/download PDF
26. Fezolinetant for the treatment of vasomotor symptoms associated with menopause: a meta-analysis.
- Author
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Chavez, Matheus Pedrotti, Pasqualotto, Eric, Ferreira, Rafael Oliva Morgado, Hohl, Alexandre, de Moraes, Francisco Cezar Aquino, Schmidt, Pedro Henrique Siedschlag, Rodrigues, Anna Luíza Soares de Oliveira, and de Sa, Joao Roberto
- Subjects
SLEEP interruptions ,MENOPAUSE ,POSTMENOPAUSE ,RANDOMIZED controlled trials ,QUALITY of life - Abstract
Copyright of Climacteric is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2024
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27. Efficacy of the hybrid closed-loop insulin delivery system in children and adolescents with type 1 diabetes: a meta-analysis with trial sequential analysis
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Ferreira, Rafael Oliva Morgado, primary, Trevisan, Talita, additional, Pasqualotto, Eric, additional, Schmidt, Pedro, additional, Chavez, Matheus Pedrotti, additional, Watanabe, Janine Midori Figueiredo, additional, and Sande-Lee, Simone van de, additional
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- 2024
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28. La voix du peuple dans les registres de délibérations castillans à la fin du Moyen Âge
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Herrer, Hipólito Rafael Oliva, primary
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- 2021
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29. PD-1/PD-L1 Inhibitors plus Chemotherapy Versus Chemotherapy Alone for Resectable Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
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Pasqualotto, Eric, primary, Moraes, Francisco Cezar Aquino de, additional, Chavez, Matheus Pedrotti, additional, Souza, Maria Eduarda Cavalcanti, additional, Rodrigues, Anna Luíza Soares de Oliveira, additional, Ferreira, Rafael Oliva Morgado, additional, Lopes, Lucca Moreira, additional, Almeida, Artur Menegaz de, additional, Fernandes, Marianne Rodrigues, additional, and Santos, Ney Pereira Carneiro dos, additional
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- 2023
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30. Endoscopic Third Ventriculostomy versus Ventriculoperitoneal Shunt in Patients with Obstructive Hydrocephalus: An Updated Systematic Review and Meta-Analysis
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Pasqualotto, Eric, additional, Schmidt, Pedro Henrique Siedschlag, additional, Ferreira, Rafael Oliva Morgado, additional, Chavez, Matheus Pedrotti, additional, and da Silva, Fernanda Feuerharmel Soares, additional
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- 2023
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31. BIOATIVIDADE DE METABÓLITOS VOLÁTEIS DE Trichoderma spp. CONTRA Fusarium oxysporum f. sp. cubense
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Oliveira, Maria Muritiba de, primary, Trocoli, Rafael Oliva, additional, Evangelista, Pricila Fagundes, additional, Dias, Ester Doanni da Silva Ferreira, additional, Nascimento, Rozilda Pereira do, additional, Matos, Thaylanne Alcântara, additional, and Silva, José Luiz dos Santos, additional
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- 2020
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32. Standards in semen examination: publishing reproducible and reliable data based on high-quality methodology
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Lars Björndahl, Christopher L R Barratt, David Mortimer, Ashok Agarwal, Robert J Aitken, Juan G Alvarez, Natalie Aneck-Hahn, Stefan Arver, Elisabetta Baldi, Lluís Bassas, Florence Boitrelle, Riana Bornman, Douglas T Carrell, José A Castilla, Gerardo Cerezo Parra, Jerome H Check, Patricia S Cuasnicu, Sally Perreault Darney, Christiaan de Jager, Christopher J De Jonge, Joël R Drevet, Erma Z Drobnis, Stefan S Du Plessis, Michael L Eisenberg, Sandro C Esteves, Evangelini A Evgeni, Alberto Ferlin, Nicolas Garrido, Aleksander Giwercman, Ilse G F Goovaerts, Trine B Haugen, Ralf Henkel, Lars Henningsohn, Marie-Claude Hofmann, James M Hotaling, Piotr Jedrzejczak, Pierre Jouannet, Niels Jørgensen, Jackson C Kirkman Brown, Csilla Krausz, Maciej Kurpisz, Ulrik Kvist, Dolores J Lamb, Hagai Levine, Kate L Loveland, Robert I McLachlan, Ali Mahran, Liana Maree, Sarah Martins da Silva, Michael T Mbizvo, Andreas Meinhardt, Roelof Menkveld, Sharon T Mortimer, Sergey Moskovtsev, Charles H Muller, Maria José Munuce, Monica Muratori, Craig Niederberger, Cristian O’Flaherty, Rafael Oliva, Willem Ombelet, Allan A Pacey, Michael A Palladino, Ranjith Ramasamy, Liliana Ramos, Nathalie Rives, Eduardo Rs Roldan, Susan Rothmann, Denny Sakkas, Andrea Salonia, Maria Cristina Sánchez-Pozo, Rosanna Sapiro, Stefan Schlatt, Peter N Schlegel, Hans-Christian Schuppe, Rupin Shah, Niels E Skakkebæk, Katja Teerds, Igor Toskin, Herman Tournaye, Paul J Turek, Gerhard van der Horst, Monica Vazquez-Levin, Christina Wang, Alex Wetzels, Theodosia Zeginiadou, Armand Zini, Faculty of Medicine and Pharmacy, Clinical sciences, Biology of the Testis, Centre for Reproductive Medicine - Gynaecology, Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), CHU Rouen, Normandie Université (NU), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Neuroendocrine, Endocrine and Germinal Differentiation Communication (NorDic), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Björndahl, L, Barratt, Clr, Mortimer, D, Agarwal, A, Aitken, Rj, Alvarez, Jg, Aneck-Hahn, N, Arver, S, Baldi, E, Bassas, L, Boitrelle, F, Bornman, R, Carrell, Dt, Castilla, Ja, Cerezo Parra, G, Check, Jh, Cuasnicu, P, Darney, Sp, de Jager, C, De Jonge, Cj, Drevet, Jr, Drobnis, Ez, Du Plessis, S, Eisenberg, Ml, Esteves, Sc, Evgeni, Ea, Ferlin, A, Garrido, N, Giwercman, A, Goovaerts, Igf, Haugen, Tb, Henkel, R, Henningsohn, L, Hofmann, Mc, Hotaling, Jm, Jedrzejczak, P, Jouannet, P, Jørgensen, N, Kirkman Brown, Jc, Krausz, C, Kurpisz, M, Kvist, U, Lamb, Dj, Levine, H, Loveland, Kl, Mclachlan, Ri, Mahran, A, Maree, L, Martins da Silva, S, Mbizvo, Mt, Meinhardt, A, Menkveld, R, Mortimer, St, Moskovtsev, S, Muller, Ch, Munuce, Mj, Muratori, M, Niederberger, C, O'Flaherty, C, Oliva, R, Ombelet, W, Pacey, Aa, Palladino, Ma, Ramasamy, R, Ramos, L, Rives, N, Roldan, Er, Rothmann, S, Sakkas, D, Salonia, A, Sánchez-Pozo, Mc, Sapiro, R, Schlatt, S, Schlegel, Pn, Schuppe, Hc, Shah, R, Skakkebæk, Ne, Teerds, K, Toskin, I, Tournaye, H, Turek, Pj, van der Horst, G, Vazquez-Levin, M, Wang, C, Wetzels, A, Zeginiadou, T, Zini, A., Pacey, Allan/0000-0002-4387-8871, Arver, Stefan/0000-0002-2925-355X, Mortimer, David/0000-0002-0638-2893, Barratt, christopher/0000-0003-0062-9979, Kirkman-Brown, Jackson, C/0000-0003-2833-8970, Bjorndahl, Lars/0000-0002-4709-5807, Baldi, Elisabetta/0000-0003-1808-3097, Aitken, Robert John/0000-0002-9152-156X, Bjorndahl, Lars, Barratt, Christopher L. R., Mortimer, David, Agarwal, Ashok, Aitken, Robert J., Alvarez, Juan G., Aneck-Hahn, Natalie, Arver, Stefan, Baldi, Elisabetta, Bassas, Lluis, Boitrelle, Florence, Bornman, Riana, Carrell, Douglas T., Castilla, Jose A., Cerezo Parra, Gerardo, Check, Jerome H., Cuasnicu, Patricia S., Darney, Sally Perreault, de Jager, Christiaan, De Jonge, Christopher J., Drevet, Joel R., Drobnis, Erma Z., Du Plessis, Stefan S., Eisenberg, Michael L., Esteves, Sandro C., Evgeni, Evangelini A., Ferlin, Alberto, Garrido, Nicolas, Giwercman, Aleksander, Goovaerts, Ilse G. F., Haugen, Trine B., Henkel, Ralf, Henningsohn, Lars, Hofmann, Marie-Claude, Hotaling, James M., Jedrzejczak, Piotr, Jouannet, Pierre, Jorgensen, Niels, Brown, Jackson C. Kirkman, Krausz, Csilla, Kurpisz, Maciej, Kvist, Ulrik, Lamb, Dolores J., Levine, Hagai, Loveland, Kate L., McLachlan, Robert, I, Mahran, Ali, Maree, Liana, da Silva, Sarah Martins, Mbizvo, Michael T., Meinhardt, Andreas, Menkveld, Roelof, Mortimer, Sharon T., Moskovtsev, Sergey, Muller, Charles H., Jose Munuce, Maria, Muratori, Monica, Niederberger, Craig, O'Flaherty, Cristian, Oliva, Rafael, OMBELET, Willem, Pacey, Allan A., Palladino, Michael A., Ramasamy, Ranjith, Ramos, Liliana, Rives, Nathalie, Roldan, Eduardo Rs, Rothmann, Susan, Sakkas, Denny, Salonia, Andrea, Cristina Sanchez-Pozo, Maria, Sapiro, Rosanna, Schlatt, Stefan, Schlegel, Peter N., Schuppe, Hans-Christian, Shah, Rupin, Skakkebaek, Niels E., Teerds, Katja, Toskin, Igor, Tournaye, Herman, Turek, Paul J., van der Horst, Gerhard, Vazquez-Levin, Monica, Wang, Christina, Wetzels, Alex, Zeginiadou, Theodosia, and Zini, Armand
- Subjects
Reproducitibility ,[SDV]Life Sciences [q-bio] ,andrology ,basic semen examination ,journal requirements ,laboratory training ,patient security ,quality control ,reproducibility ,reproductive medicine ,science development ,standardized laboratory procedures ,Humans ,Reproducibility of Results ,Publishing ,Semen ,Semen Analysis ,Andrology ,Obstetrics & Reproductive Medicine ,Biology ,11 Medical and Health Sciences ,Reproductive Biology ,Science & Technology ,Rehabilitation ,Obstetrics & Gynecology ,Obstetrics and Gynecology ,Reproductive Medicine ,16 Studies in Human Society ,Human and Animal Physiology ,Fysiologie van Mens en Dier ,Human medicine ,Life Sciences & Biomedicine - Abstract
Biomedical science is rapidly developing in terms of more transparency, openness and reproducibility of scientific publications. This is even more important for all studies that are based on results from basic semen examination. Recently two concordant documents have been published: the 6th edition of the WHO Laboratory Manual for the Examination and Processing of Human Semen, and the International Standard ISO 23162:2021. With these tools, we propose that authors should be instructed to follow these laboratory methods in order to publish studies in peer-reviewed journals, preferable by using a checklist as suggested in an Appendix to this article.
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- 2022
33. La voix des assemblées
- Author
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Bortoluzzi, Daniele, Challet, Vincent, Coquelin, Morwenna, Durand, Stéphane, Faini, Enrico, Félicité, Indravati, Germain, Lionel, Hébert, Michel, Herrer, Hipólito Rafael Oliva, Lett, Didier, Mabboux, Carole, Magnani, Matteo, Maret, Auderic, Milian, Laura Miquel, Nadrigny, Xavier, Otchakovsky-Laurens, François, Rager, Cléo, Richard, Olivier, Sala, Albert Reixach, Senatore, Francesco, Tanzini, Lorenzo, Terenzi, Pierluigi, Varitille, Florie, Vidoni, Nicolas, Otchakovsky-Laurens, François, and Verdon, Laure
- Subjects
Europe méridionale ,histoire médiévale ,sources historiques ,History ,délibérations ,histoire moderne ,conseils de ville ,assemblée ,institutions municipales - Abstract
À l’heure où les formes de la démocratie représentative sont interrogées de différentes manières, que peuvent nous apprendre les expériences de délibération communale développées au sein des communautés urbaines médiévales et modernes ? Les registres de délibérations forment un corpus très abondant depuis la fin du Moyen Âge. Leur production, en Europe méridionale puis occidentale, a accompagné le développement des formes écrites de l’administration. Or, à l’échelle du gouvernement des sociétés médiévales et modernes, les écritures des conseils de ville permettent de pénétrer les processus de la prise de décision. Les études ici contenues interrogent la diffusion et l’adaptation locale des cultures politiques européennes. Elles prolongent les avancées les plus récentes de la recherche sur le pouvoir de l’écrit, sur un terrain nouveau. Il s’agit ici de la première synthèse sur les sources historiques sans doute les plus abondantes et les plus continues en histoire urbaine. Apparemment banals, les registres de délibérations ont été jusque-là utilisés par les historiens sans y prêter toute l’attention qu’ils méritaient. Cet ouvrage mutualise les approches méthodologiques. Le collectif de chercheurs réunis forge ainsi les outils d’un comparatisme européen, à l’échelle urbaine. La perspective choisie est celle de la longue durée, en examinant l’évolution politique et scripturale des institutions municipales du XIIIe au XVIIIe siècle.
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- 2022
34. La voix du peuple dans les registres de délibérations castillans à la fin du Moyen Âge
- Author
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Herrer, Hipólito Rafael Oliva
- Subjects
Europe méridionale ,histoire médiévale ,sources historiques ,History ,délibérations ,histoire moderne ,conseils de ville ,assemblée ,institutions municipales - Abstract
L’étude systématique du fonctionnement politique des villes de la Couronne de Castille commence dans la première moitié des années quatre-vingt-dix du siècle dernier, et ceci dans un contexte très particulier. À cette époque, l’université espagnole augmente de manière significative l’effectif de son corps enseignant. C’est à ce moment-là que les archives municipales ont commencé à être systématiquement étudiées et qu’une série d’études monographiques sur la structure institutionnelle et la dy...
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- 2022
35. Fezolinetant for VMS: a balanced view on efficacy and safety needed – author's reply.
- Author
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Chavez, Matheus Pedrotti, Pasqualotto, Eric, Ferreira, Rafael Oliva Morgado, Hohl, Alexandre, de Moraes, Francisco Cezar Aquino, Schmidt, Pedro Henrique Siedschlag, Rodrigues, Anna Luíza Soares de Oliveira, and de Sa, Joao Roberto
- Subjects
ENDOMETRIAL cancer ,POSTMENOPAUSE ,HORMONE therapy ,DISEASE risk factors ,PATIENT monitoring - Abstract
This document is a reply to comments made on a previous article about the use of fezolinetant for treating vasomotor symptoms associated with menopause. The US Food and Drug Administration (FDA) investigated the potential increased risk of neoplasms (abnormal growth of tissue) with fezolinetant and found that while there was an apparent dose-response for malignancy, there were no consistent patterns related to drug exposure duration, body system, or cancer type. The authors of the reply acknowledge the increased incidence of neoplasms in patients treated with fezolinetant, but they argue that comparing the data between the fezolinetant and placebo groups with unequal follow-up durations may lead to skewed conclusions. They recommend additional long-term safety studies and close monitoring of patients using fezolinetant to make better-informed decisions about managing menopause symptoms. [Extracted from the article]
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- 2024
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36. DOT1L regulates chromatin reorganization and gene expression during sperm differentiation
- Author
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Mélina Blanco, Laila El Khattabi, Clara Gobé, Marion Crespo, Manon Coulée, Alberto de la Iglesia, Côme Ialy‐Radio, Clementine Lapoujade, Maëlle Givelet, Marion Delessard, Ivan Seller‐Corona, Kosuke Yamaguchi, Nadège Vernet, Fred Van Leeuwen, Alban Lermine, Yuki Okada, Romain Daveau, Rafael Oliva, Pierre Fouchet, Ahmed Ziyyat, Delphine Pflieger, Julie Cocquet, Medical Biology, AII - Cancer immunology, and CCA - Cancer biology and immunology
- Subjects
flagellum development ,histone-to-protamine transition ,Genetics ,H3K79 methylation ,gene regulation ,Molecular Biology ,Biochemistry ,spermatogenesis - Abstract
Spermatozoa have a unique genome organization: their chromatin is almost completely devoid of histones and is formed instead of protamines which confer a high level of compaction and preserve paternal genome integrity until fertilization. Histone-to-protamine transition takes place in spermatids and is indispensable for the production of functional sperm. Here we show that the H3K79-methyltransferase DOT1L controls spermatid chromatin remodelling and subsequent reorganization and compaction of spermatozoon genome. Using a mouse model in whichDot1lis knocked-out (KO) in postnatal male germ cells, we found thatDot1l-KO sperm chromatin is less compact and has an abnormal content, characterized by the presence of transition proteins, immature protamine 2 forms and a higher level of histones. Proteomics and transcriptomics analyses performed on spermatids reveal thatDot1l-KO modifies the chromatin prior to histone removal, and leads to the deregulation of genes involved in flagellum formation and apoptosis during spermatid differentiation. As a consequence of these chromatin and gene expression defects,Dot1l-KO spermatozoa have less compact heads and are less motile which results in impaired fertility.
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- 2022
37. Insights into the sperm chromatin and implications for male infertility from a protein perspective
- Author
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Alberto de la Iglesia, Meritxell Jodar, Rafael Oliva, and Judit Castillo
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Cromatina ,Espermatozoides ,Esterilitat masculina ,Male sterility ,Proteins ,Epigenetics ,Epigenètica ,Proteïnes ,Spermatozoa ,Chromatin - Abstract
Male germ cells undergo an extreme but fascinating process of chromatin remodeling that begins in the testis during the last phase of spermatogenesis and continues through epididymal sperm maturation. Most of the histones are replaced by small proteins named protamines, whose high basicity leads to a tight genomic compaction. This process is epigenetically regulated at many levels, not only by posttranslational modifications, but also by readers, writers, and erasers, in a context of a highly coordinated postmeiotic gene expression program. Protamines are key proteins for acquiring this highly specialized chromatin conformation, needed for sperm functionality. Interestingly, and contrary to what could be inferred from its very specific DNA-packaging function across protamine-containing species, human sperm chromatin contains a wide spectrum of protamine proteoforms, including truncated and posttranslationally modified proteoforms. The generation of protamine knock-out models revealed not only chromatin compaction defects, but also collateral sperm alterations contributing to infertile phenotypes, evidencing the importance of sperm chromatin protamination toward the generation of a new individual. The unique features of sperm chromatin have motivated its study, applying from conventional to the most ground-breaking techniques to disentangle its peculiarities and the cellular mechanisms governing its successful conferment, especially relevant from the protein point of view due to the important epigenetic role of sperm nuclear proteins. Gathering and contextualizing the most striking discoveries will provide a global understanding of the importance and complexity of achieving a proper chromatin compaction and exploring its implications on postfertilization events and beyond. This article is categorized under: Reproductive System Diseases > Genetics/Genomics/Epigenetics Reproductive System Diseases > Molecular and Cellular Physiology.
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- 2022
38. Proposal for flicker measurement and evaluation in grid-connected low-power wind turbines
- Author
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Ariel Agnello, Ruben Bufanio, Damian Marasco, Gustavo Monte, Norberto Scarone, Mariano Amadio, Rafael Oliva, Andres Zappa, and Carlos Canon
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- 2022
39. Semen sampling as a simple, noninvasive surrogate for prostate health screening
- Author
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Mireia Musquera, Panagiotis Ntostis, David Iles, Rafael Oliva, Lourdes Mengual, David Miller, Asif Muneer, Norman J. Maitland, and Gisela Lorente
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Screening test ,Biopsy ,Urology ,Semen ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Prostate ,Vasectomy ,medicine ,Humans ,Sampling (medicine) ,Health screening ,030219 obstetrics & reproductive medicine ,medicine.diagnostic_test ,business.industry ,Prostatic Neoplasms ,nutritional and metabolic diseases ,medicine.disease ,030104 developmental biology ,medicine.anatomical_structure ,Reproductive Medicine ,business - Abstract
The detection rates for prostate cancer (pCa) by invasive biopsy are high, fully justifying its use in confirmatory testing. False-positive results of prior, relatively insensitive screening tests, however, can lead to expensive and often unnecessary surgery. Several reports have suggested the potential use of the ejaculate to screen for prostate conditions. Hitherto, the potential impact of sterilization on the diagnostic potential of seminal plasma screening has not been examined. Herein, we report cellular and molecular comparisons of semen samples obtained from normal (N = 5), vasectomized (N = 5) and prostate pathology patients (N = 4; confirmed by a biopsy) that were centrifuged over 60% PureSperm cushions. Non-penetrating cells were washed prior to immunocytochemistry with prostatic epithelial cell markers including PSMA, NKX3.1 and CD24. KRT18 was used to highlight epithelial cells in these samples. RNA sequencing was then used to identify differentially expressed small RNAs associated with vasectomy and prostate pathology. Specific gene transcripts were confirmed by RT-qPCR. PMSA
- Published
- 2021
40. Histopathology of recurrent Steel syndrome in fetuses caused by novel variants of COL27A1 gene
- Author
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Berta Campos, Alfons Nadal, Virginia Borobio Florián, Maria Segura Puimedon, Montse Pauta, Anna Vallmajó Fita, Rafael Oliva, Olga Gómez Del Rincón, Gerard Frigola, and Antoni Borrell
- Subjects
Adult ,Male ,0301 basic medicine ,Pathology ,medicine.medical_specialty ,Heredity ,Fibrillar Collagens ,Gestational Age ,Biology ,Osteochondrodysplasias ,Compound heterozygosity ,Pathology and Forensic Medicine ,03 medical and health sciences ,symbols.namesake ,Fetus ,0302 clinical medicine ,Pregnancy ,Recurrence ,Exome Sequencing ,medicine ,Humans ,Genetic Predisposition to Disease ,Molecular Biology ,Exome sequencing ,Sanger sequencing ,Cartilage ,Genetic Variation ,High-Throughput Nucleotide Sequencing ,Abortion, Induced ,Histology ,Syndrome ,Cell Biology ,General Medicine ,medicine.disease ,Osteochondrodysplasia ,Pedigree ,Phenotype ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,symbols ,Female ,Histopathology - Abstract
Steel syndrome (STLS) encompasses characteristic facies, dwarfness, irreducible bilateral hip and radial head dislocation, and carpal bone coalition due to COL27A1 mutations. Two consecutive pregnancies in a non-consanguineous couple were terminated because of severe fetal anomalies. Complete autopsies with microscopic exam were performed on both fetuses. Next-generation-based clinical exome sequencing was applied to the first fetus. Exome sequencing results, parental segregation, and affection of the second fetus were confirmed by Sanger sequencing. Both fetuses had signs consistent with STLS. Bilateral capitulum humeri absence explained radial head dislocation in STLS. Metaphyseal cartilage showed severe disorganization. Resting cartilage was hypercellular, organized in irregular nests limited by acellular matrix. Two variants in COL27A1 (c.2548G>A -p.Gly850Arg- and c.3249+1G> T) were found in both fetuses in compound heterozygosity with parental Mendelian segregation. This is the first report to include histology of STLS. The COL27A1 variants here described increase the number of mutations associated with STLS.
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- 2021
41. Gordon Henry Dixon. 25 March 1930 — 24 July 2016
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Rafael Oliva, Stephen A. Krawetz, and GHD Consortium
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0303 health sciences ,03 medical and health sciences ,030219 obstetrics & reproductive medicine ,0302 clinical medicine ,General Medicine ,Sociology ,030304 developmental biology ,Management - Abstract
Gordon H. Dixon was a highly influential scientist who excelled in all the stages of his career and in each laboratory of every institution at which he was a member. Gordon began his graduate career at the University of Cambridge and completed his studies at the University of Toronto on the subject of transpeptidation reactions in biological systems. At an early stage of his career, he developed the technique of starch gel electrophoresis with Oliver Smithies and made important discoveries on the structure of human haptoglobins. Subsequently, Gordon contributed to the determination of the structure and active sites and mechanisms of action of trypsin and chymotrypsin and made seminal discoveries related to understanding the structure of the protein hormone insulin. However, he is best known for his later studies on the regulation of protamine genes and chromatin transitions in spermatogenesis. He is often considered to be the father of the protamine molecular biology underlying this gene system and his research is continually cited to this day. Gordon contributed to the identification and sequencing of the protamine genes, the discovery that methionine was required for initiation of protamine synthesis, understanding the roles of histone hyperacetylation and protamine phosphorylation, and the generation of the highly compact nucleoprotamine structure present in sperm, primarily using trout as a model system. Gordon is fondly remembered as a brilliant and very generous scientist by all his mentees, representing all levels from undergraduates to PhD and postdoctoral fellows, who provided a scientifically stimulating atmosphere in which they could develop their careers. From a more personal perspective, he also had a fun side and was devoted to his family. Gordon was a person who, owing to his legacy of great science and his fundamental humanity, still lives in the memory of many people.
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- 2020
42. Hardware and firmware design and implementation of twin 8- and 32-bit microcontroller boards for research and educational applications
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Rafael Oliva
- Abstract
This document describes the design and implementation sequence of both hardware and firmware components of two microcontroller boards of 8 and 32 bit architectures, which use similar form factor and share common input/output devices and recently developed web-based user interfaces. Both have been applied mainly to educational and research systems in renewable energy. The focus has been on increasing reliability in the hardware aspects and using a set of in-house C language coding rules for new firmware development and legacy code refactoring. Testing of the low-level drivers, and use of automated tools such as Ceedling for higher level module testing is also described.
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- 2022
43. Resolution of subclinical porphyria cutanea tarda after hepatitis C eradication with direct-acting anti-virals
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Anna Pocurull, Jordi To-Figueras, Xavier Forns, Paula Aguilera, Sabela Lens, Zoe Mariño, Celia Badenas, Rafael Oliva, Sergio Rodríguez-Tajes, Concepció Bartres, and Lydia Sastre
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Male ,Porphyria Cutanea Tarda ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,Porphyrins ,Hepatitis C virus ,Urinary system ,medicine.disease_cause ,Antiviral Agents ,Gastroenterology ,Asymptomatic ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,Porphyria cutanea tarda ,030212 general & internal medicine ,Aged ,Subclinical infection ,Hepatitis ,Hepatology ,business.industry ,Hepatitis C ,Middle Aged ,medicine.disease ,Porphyria ,Female ,030211 gastroenterology & hepatology ,medicine.symptom ,business - Abstract
Background Hepatitis C virus (HCV) is a risk factor for porphyria cutanea tarda (PCT), a rare disease originating in the liver characterised by overproduction of porphyrins. Although hepatitis C infection is highly prevalent among patients with porphyria, only a minority of hepatitis C patients develop PCT. Aims To explore the presence of porphyrin abnormalities in a cohort of asymptomatic hepatitis C-infected patients and the impact of anti-viral therapy. Methods Eighty-four consecutive patients with HCV infection treated with direct-acting antivirals after 1 January 2018 were longitudinally evaluated for the presence of porphyrin abnormalities. Those patients with biochemical abnormalities at baseline were additionally evaluated at follow-up. Porphyrins in urine were screened by fluorometry and isomer separation was performed by liquid chromatography. Results In five patients, all of them asymptomatic, porphyrin profile abnormalities were detected: three presented significant increased urinary porphyrins with a typical PCT profile, and two showed normal levels of urinary porphyrins, but abnormal porphyria-like profiles. Urine evaluation after hepatitis C cure showed complete normalisation of the urinary porphyrins in all patients, confirming the biochemical cure of the disease. Conclusions We document the existence of rare cases of hepatitis C-infected patients with significant uroporphyrinuria in the absence of dermatological manifestations. Anti-viral therapy normalises the biochemical disorder, preventing patients from presenting PCT associated complications.
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- 2020
44. ANDRONET: A new European network to boost research coordination, education and public awareness in andrology
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Rafael Oliva, Csilla Krausz, and Ewa Rajpert‐De Meyts
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Endocrinology ,Reproductive Medicine ,Endocrinology, Diabetes and Metabolism ,Urology ,Andrology - Published
- 2021
45. Novel phospholipase C zeta 1 mutations associated with fertilization failures after ICSI
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Anna Ferrer-Vaquer, Filippo Zambelli, Rafael Oliva, Marc Torra-Massana, Rita Vassena, Mercè Durban, Amelia Rodríguez, David Cornet-Bartolomé, and Montserrat Barragán
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Adult ,Male ,DNA Mutational Analysis ,Biology ,medicine.disease_cause ,Andrology ,03 medical and health sciences ,Phosphoinositide Phospholipase C ,0302 clinical medicine ,Human fertilization ,Pregnancy ,medicine ,Humans ,Sperm Injections, Intracytoplasmic ,Treatment Failure ,Cell Shape ,030304 developmental biology ,0303 health sciences ,Mutation ,030219 obstetrics & reproductive medicine ,Pronucleus ,Point mutation ,Rehabilitation ,Obstetrics and Gynecology ,Oocyte activation ,Nurse anesthetist ,Oocyte ,Spermatozoa ,Sperm ,Semen Analysis ,medicine.anatomical_structure ,Reproductive Medicine ,Oocytes ,Sperm Motility ,Female ,business ,business.employer - Abstract
STUDY QUESTIONAre phospholipase C zeta 1 (PLCZ1) mutations associated with fertilization failure (FF) after ICSI?SUMMARY ANSWERNew mutations in the PLCZ1 sequence are associated with FFs after ICSI.WHAT IS KNOWN ALREADYFF occurs in 1–3% of ICSI cycles, mainly due to oocyte activation failure (OAF). The sperm PLCζ/PLCZ1 protein hydrolyzes phosphatidylinositol (4, 5)-bisphosphate in the oocyte, leading to intracellular calcium release and oocyte activation. To date, few PLCZ1 point mutations causing decreased protein levels or activity have been linked to FF. However, functional alterations of PLCζ/PLCZ1 in response to both described and novel mutations have not been investigated.STUDY DESIGN, SIZE, DURATIONWe performed a study including 37 patients presenting total or partial FF (fertilization rate (FR), ≤25%) after ICSI occurring between 2014 and 2018.PARTICIPANTS/MATERIALS, SETTING, METHODSPatients were divided into two groups based on oocyte evaluation 19 h post ICSI: FF due to a defect in oocyte activation (OAF, n = 22) and FF due to other causes (‘no-OAF’, n = 15). Samples from 13 men with good fertilization (FR, >50%) were used as controls. PLCζ/PLCZ1 protein localization and levels in sperm were evaluated by immunofluorescence and western blot, respectively. Sanger sequencing on genomic DNA was used to identify PLCZ1 mutations in exonic regions. The effect of the mutations on protein functionality was predicted in silico using the MODICT algorithm. Functional assays were performed by cRNA injection of wild-type and mutated forms of PLCZ1 into human in vitro matured metaphase II oocytes, and fertilization outcomes (second polar body extrusion, pronucleus appearance) scored 19 h after injection.MAIN RESULTS AND THE ROLE OF CHANCEIn the OAF group, 12 (54.6%) patients carried at least one mutation in the PLCZ1 coding sequence, one patient out of 15 (6.7%) in the no-OAF group (P 60%) in patients carrying PLCZ1 mutations (n = 10) after assisted oocyte activation (AOA), with seven patients achieving pregnancy and live birth.LIMITATIONS, REASONS FOR CAUTIONCaution should be exerted when comparing the cRNA injection results with fertilization outcomes after ICSI, especially in patients presenting mutations in heterozygosis.WIDER IMPLICATIONS OF THE FINDINGSPLCZ1 mutations were found in high frequency in patients presenting OAF. Functional analysis of three mutations in human oocytes confirms alteration of PLCζ/PLCZ1 activity and their likely involvement in impaired oocyte activation. Our results suggest that PLCZ1 gene sequencing could be useful as a tool for the diagnosis and counseling of couples presenting FF after ICSI due to OAF.STUDY FUNDING/COMPETING INTEREST(S)This work was supported by intramural funding of Clínica EUGIN, by the Secretary for Universities and Research of the Ministry of Economy and Knowledge of the Government of Catalonia (GENCAT 2015 DI 049 to M. T.-M. and GENCAT 2015 DI 048 to D. C.-B.) and by the Torres Quevedo Program from the Spanish Ministry of Economy and Competitiveness to A. F.-V. No competing interest declared.
- Published
- 2019
46. Global Proteomic and Methylome Analysis in Human Induced Pluripotent Stem Cells Reveals Overexpression of a Human TLR3 Affecting Proper Innate Immune Response Signaling
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Orleigh Addeleccia Bogle, Anna Boronat Barado, Iñaki Alvarez, Montserrat Codina‐Pascual, Jovita Mezquita-Pla, Ana Belén Alvarez-Palomo, Ernst J. Wolvetang, Raul Delgado-Morales, Rafael Oliva, Manel Esteller, Antonella Consiglio, Dolores Jaraquemada, Dmitry A. Ovchinnikov, Manel Juan, Michael J. Edel, Marti Farrera Sal, Sebastian Moran, Jordi Requena, Universitat de Barcelona, RS: MHeNs - R3 - Neuroscience, and Psychiatrie & Neuropsychologie
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0301 basic medicine ,Proteomics ,MHC-I ,Cytokine ,Stem cells ,IMMUNOGENICITY ,Toll like receptor ,Embryonic Stem Cells/Induced Pluripotent Stem Cells ,ACTIVATION ,Epigenome ,0302 clinical medicine ,Resposta immunitària ,Induced pluripotent stem cells ,Citoquines ,Innate ,Induced pluripotent stem cell ,NEURONS ,Toll-like receptor ,ROLES ,Human leukocyte antigen ,BIOINFORMATICS ,Inflamació ,Neural stem cell ,3. Good health ,Cell biology ,Immune response ,Inflammation ,Neural stem cells ,Humans ,Immunity, Innate ,Induced Pluripotent Stem Cells ,Signal Transduction ,Toll-Like Receptor 3 ,Molecular Medicine ,Cytokines ,Stem cell ,Cèl·lules mare ,Reprogramming ,EXPRESSION ,MHC‐I ,chemical and pharmacologic phenomena ,Biology ,03 medical and health sciences ,Immune system ,Innate immune system ,Immunity ,Cell Biology ,030104 developmental biology ,Cell culture ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
Altres ajuts: the E-Rare (ERA-Net for research programs on rare diseases) and EuroRETT (a European network on Rett syndrome, funded by the European Commission under its 6th Framework Program since 2006) When considering the clinical applications of autologous cell replacement therapy of human induced pluripotent stem cells (iPSC)-derived cells, there is a clear need to better understand what the immune response will be before we embark on extensive clinical trials to treat or model human disease. We performed a detailed assessment comparing human fibroblast cell lines (termed F1) reprogrammed into human iPSC and subsequently differentiated back to fibroblast cells (termed F2) or other human iPSC-derived cells including neural stem cells (NSC) made from either retroviral, episomal, or synthetic mRNA cell reprogramming methods. Global proteomic analysis reveals the main differences in signal transduction and immune cell protein expression between F1 and F2 cells, implicating wild type (WT) toll like receptor protein 3 (TLR3). Furthermore, global methylome analysis identified an isoform of the human TLR3 gene that is not epigenetically reset correctly upon differentiation to F2 cells resulting in a hypomethylated transcription start site in the TLR3 isoform promoter and overexpression in most human iPSC-derived cells not seen in normal human tissue. The human TLR3 isoform in human iPSC-NSC functions to suppress NF-KB p65 signaling pathway in response to virus (Poly IC), suggesting suppressed immunity of iPSC-derived cells to viral infection. The sustained WT TLR3 and TLR3 isoform overexpression is central to understanding the altered immunogenicity of human iPSC-derived cells calling for screening of human iPSC-derived cells for TLR3 expression levels before applications. Stem Cells 2019;37:476-488.
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- 2019
47. Recomendaciones para el estudio genético de la pareja con alteraciones en la reproducción
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Alonso Cerezo, Concepción, Carmen Cañadas Gálvez, M., de la Fuente Hernández, Luis Alfonso, García-Ochoa, Carlos, Sagredo, José Miguel García, Villafáñez, Victoria González, González, Mercedes Marcos, Virgili, Rafael Oliva, and Clemente, Maria Orera
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- 2009
- Full Text
- View/download PDF
48. Special Issue in Honor of Gordon H. Dixon
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J. Christopher States, Helen G. Tempest, Rod Balhorn, Rafael Oliva, Stephen A. Krawetz, Jovita Mezquita-Pla, Kenneth C. Kleene, and Peter L. Davies
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medicine.medical_specialty ,010504 meteorology & atmospheric sciences ,Reproductive Medicine ,Urology ,Honor ,010102 general mathematics ,Reproductive medicine ,medicine ,Sociology ,0101 mathematics ,01 natural sciences ,Classics ,0105 earth and related environmental sciences - Abstract
This issue of Systems Biology in Reproductive Medicine (SBiRM) is dedicated in honor of Dr. Gordon H. Dixon’s (25 March 1930 – 24 July 2016) many contributions to our understanding of how nuclear c...
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- 2018
49. « Vols, force et mort d’hommes ». La violence seigneuriale dans le royaume de Castille à la fin du Moyen Âge
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Hipólito Rafael Oliva Herrer
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communities ,Criminal law and procedure ,Moyen Âge ,violence ,communautés ,K5000-5582 ,noblesse ,nobility ,Middle Ages ,Castile - Abstract
Cet article étudie les formes de violence nobiliaire contre les communautés rurales dans la Castille des XIVe et XVe siècles et le discours qui sert à les qualifier. De ce point de vue, l’article montre la persistance d’une violence seigneuriale durant la période, exprimée en grande partie dans les moments de conflit politique ouvert dans le royaume, qu’on ne saurait réduire à l’expression d’une logique identitaire nobiliaire et qui révèle une tendance seigneuriale expansionniste. Toutefois, la prolifération des dénonciations de ces pratiques seigneuriales permet aussi de voir le progrès d’un cadre normatif servant à dénoncer ces pratiques habituelles comme violentes, donc illégitimes, et qui permet l’articulation de résistances. The aim of this article is to analyse both the forms of noble violence against rural communities in Castile during the XIVth and XVth centuries and the discourse used to denounce them. From this point of view, the article shows the continuity, during the period, of practices of seigniorial violence more pronounced in moments of open political conflict throughout the kingdom. This kind of violence cannot be only reduced to the expression of a noble identity and reveals an expansionist seigniorial logic. Beside, the proliferation of complaints about seigniorial violence shows the progress of a framework which permits to define these usual practices as violent, and therefore, illegitimate, and permits to articulate resistances.
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- 2021
50. Altered mitochondrial function in spermatozoa from patients with repetitive fertilization failure after ICSI revealed by proteomics
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Rita Vassena, Amelia Rodríguez, Montserrat Barragán, David Delgado-Dueñas, Marc Torra-Massana, Rafael Oliva, Ada Soler-Ventura, and Meritxell Jodar
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Adult ,Male ,Proteomics ,Urology ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,SLC25A6 ,Biology ,Mitochondrion ,SLC25A3 ,Intracytoplasmic sperm injection ,Andrology ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Human fertilization ,Western blot ,medicine ,Humans ,Sperm Injections, Intracytoplasmic ,Treatment Failure ,reproductive and urinary physiology ,Infertility, Male ,030219 obstetrics & reproductive medicine ,medicine.diagnostic_test ,urogenital system ,Sperm ,Spermatozoa ,Mitochondria ,Reproductive Medicine ,biology.protein - Abstract
Unexplained fertilization failure (FF), occurring in 1-3% of intracytoplasmic sperm injection (ICSI) cycles, results in both psychological and financial burden for the patients. However, the molecular causes behind FF remain largely unknown. Mass spectrometry is a powerful technique to identify and quantify proteins across samples; however, no study so far has used it to dissect the proteomic signature of spermatozoa with FF after ICSI.To investigate whether sperm samples from patients suffering repetitive FF after ICSI display alterations in their protein content.Seventeen infertile men were included: 5 patients presented FF in ≥3 consecutive ICSI cycles, while 12 patients had a fertilization rate75% (controls). Individual sperm samples were subjected to 2D-LC-MS/MS. Both conventional and novel statistical approaches were used to identify differentially abundant proteins. Additionally, analysis of mitochondrial and proteasomal abundance and activity were performed, using Western blot, FACS analysis of JC-1 staining and AMC-peptide fluorometric assay.Four proteins presented lower abundance (FMR1NB, FAM209B, RAB2B, and PSMA1) in the FF group compared to controls, while five mitochondrial proteins presented higher abundance in FF (DLAT, ATP5H, SLC25A3, SLC25A6, and FH) (p 0.05). The altered abundance of mitochondrial DLAT and proteasomal PSMA1 was corroborated by Western blot. Of relevance, novel stable-protein pair analysis identified 73 correlations comprising 28 proteins within controls, while different mitochondrial proteins (ie, PDHA2, PHB2, and ATP5F1D) lost50% of these correlations in specific FF samples pointing out specific mitochondrial deregulations.This is the first proteomic analysis of spermatozoa from patients who resulted in fertilization failure after ICSI. The altered proteins, most of them related to mitochondrial function, could help to identify diagnostic/prognostic markers of fertilization failure and could further dissect the molecular paternal contribution to reach successful fertilization.Sperm samples from patients with FF after ICSI present altered abundance of different proteins, including mainly mitochondrial proteins.
- Published
- 2021
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