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1.
Cell Rep Med ; 5(3): 101449, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38508141

RESUMO

Tissue regeneration following an injury requires dynamic cell-state transitions that allow for establishing the cell identities required for the restoration of tissue homeostasis and function. Here, we present a biochemical intervention that induces an intermediate cell state mirroring a transition identified during normal differentiation of myoblasts and other multipotent and pluripotent cells to mature cells. When applied in somatic differentiated cells, the intervention, composed of one-carbon metabolites, reduces some dedifferentiation markers without losing the lineage identity, thus inducing limited reprogramming into a more flexible cell state. Moreover, the intervention enabled accelerated repair after muscle injury in young and aged mice. Overall, our study uncovers a conserved biochemical transitional phase that enhances cellular plasticity in vivo and hints at potential and scalable biochemical interventions of use in regenerative medicine and rejuvenation interventions that may be more tractable than genetic ones.


Assuntos
Músculos , Mioblastos , Camundongos , Animais , Diferenciação Celular , Mioblastos/metabolismo
2.
Stem Cell Res Ther ; 14(1): 42, 2023 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-36927767

RESUMO

BACKGROUND: The generation of induced pluripotent stem cells has opened the field of study for stem cell research, disease modeling and drug development. However, the epigenetic signatures present in somatic cells make cell reprogramming still an inefficient process. This epigenetic memory constitutes an obstacle in cellular reprogramming. Here, we report the effect of hydralazine (HYD) and valproic acid (VPA), two small molecules with proven epigenetic activity, on the expression of pluripotency genes in adult (aHF) and neonatal (nbHF) human fibroblasts. METHODS: aHF and nbHF were treated with HYD and/or VPA, and viability and gene expression assays for OCT4, NANOG, c-MYC, KLF4, DNMT1, TET3, ARID1A and ARID2 by quantitative PCR were performed. aHF and nbHF were transfected with episomal plasmid bearing Yamanaka factors (OCT4, SOX2, KLF4 and c-MYC) and exposed to HYD and VPA to determine the reprogramming efficiency. Methylation sensitive restriction enzyme (MSRE) qPCR assays were performed on OCT4 and NANOG promoter regions. Immunofluorescence assays were carried out for pluripotency genes on iPSC derived from aHF and nbHF. RESULTS: HYD upregulated the expression of OCT4 (2.5-fold) and NANOG (fourfold) genes but not c-Myc or KLF4 in aHF and had no significant effect on the expression of all these genes in nbHF. VPA upregulated the expression of NANOG (twofold) in aHF and c-MYC in nbHF, while it downregulated the expression of NANOG in nbHF. The combination of HYD and VPA canceled the OCT4 and NANOG overexpression induced by HYD in aHF, while it reinforced the effects of VPA on c-Myc expression in nbHF. The HYD-induced overexpression of OCT4 and NANOG in aHDF was not dependent on demethylation of gene promoters, and no changes in the reprogramming efficiency were observed in both cell populations despite the downregulation of epigenetic genes DNMT1, ARID1A, and ARID2 in nbHF. CONCLUSIONS: Our data provide evidence that HYD regulates the expression of OCT4 and NANOG pluripotency genes as well as ARID1A and ARID2 genes, two members of the SWI/SNF chromatin remodeling complex family, in normal human dermal fibroblasts.


Assuntos
Montagem e Desmontagem da Cromatina , Células-Tronco Pluripotentes Induzidas , Recém-Nascido , Humanos , Fator 4 Semelhante a Kruppel , Reprogramação Celular/genética , Células-Tronco Pluripotentes Induzidas/metabolismo , Fibroblastos/metabolismo , Fator 3 de Transcrição de Octâmero/genética , Fator 3 de Transcrição de Octâmero/metabolismo
3.
Sensors (Basel) ; 23(3)2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36772464

RESUMO

Designing human-machine interactive systems requires cooperation between different disciplines is required. In this work, we present a Dialogue Manager and a Language Generator that are the core modules of a Voice-based Spoken Dialogue System (SDS) capable of carrying out challenging, long and complex coaching conversations. We also develop an efficient integration procedure of the whole system that will act as an intelligent and robust Virtual Coach. The coaching task significantly differs from the classical applications of SDSs, resulting in a much higher degree of complexity and difficulty. The Virtual Coach has been successfully tested and validated in a user study with independent elderly, in three different countries with three different languages and cultures: Spain, France and Norway.


Assuntos
Comunicação , Idioma , Humanos , Idoso , Sistemas Homem-Máquina , Veículos Automotores , França
4.
J Am Coll Surg ; 235(2): 268-275, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35839401

RESUMO

BACKGROUND: Artificial intelligence (AI) applications aiming to support surgical decision-making processes are generating novel threats to ethical surgical care. To understand and address these threats, we summarize the main ethical issues that may arise from applying AI to surgery, starting from the Ethics Guidelines for Trustworthy Artificial Intelligence framework recently promoted by the European Commission. STUDY DESIGN: A modified Delphi process has been employed to achieve expert consensus. RESULTS: The main ethical issues that arise from applying AI to surgery, described in detail here, relate to human agency, accountability for errors, technical robustness, privacy and data governance, transparency, diversity, non-discrimination, and fairness. It may be possible to address many of these ethical issues by expanding the breadth of surgical AI research to focus on implementation science. The potential for AI to disrupt surgical practice suggests that formal digital health education is becoming increasingly important for surgeons and surgical trainees. CONCLUSIONS: A multidisciplinary focus on implementation science and digital health education is desirable to balance opportunities offered by emerging AI technologies and respect for the ethical principles of a patient-centric philosophy.


Assuntos
Inteligência Artificial , Princípios Morais , Consenso , Humanos
5.
Endosc Int Open ; 10(5): E679-E685, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35571467

RESUMO

Background and study aims Image-guided minimally invasive techniques have transformed the management of malignant and benign bile duct obstructions. These evolving techniques are being widely adopted and applied and hands-on training using high quality models is required to improve the proficiency of practitioners. This experimental study aimed to validate an in vivo porcine model created to simulate bile duct dilation for interventional endoscopic ultrasound (EUS) hands-on training curriculums. Materials and methods Thirty-six porcine models were involved and the procedures were performed in an experimental hybrid operating room under general anesthesia. Animals underwent endoscopic duodenal papilla clipping with several hemostatic metallic clips. After a survival period of 24 to 48 hours, the models with effective intrahepatic and extrahepatic bile duct dilatation were included in the hands-on training. Trainees and faculty were given structured evaluations of the model realism and usefulness. Results Extrahepatic bile duct and gallbladder dilation was achieved in all 36 of the models, and in 11 of the 36 models, a treatable intrahepatic duct dilatation was achieved. During the hands-on training, EUS-guided biliary drainage, EUS-guided transgastric gallbladder drainage, and EUS through-the-needle microbiopsy forceps procedures were feasible. Overall, 75 % of the experts and trainees evaluated the training as excellent. Conclusions We present a minimally invasive, reliable and time- effective model of extrahepatic dilation suitable for interventions. The model was less effective for intrahepatic ducts, which should be considered if intrahepatic biliary dilation is required for training.

6.
Discov Health Syst ; 1(1): 2, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-37521113

RESUMO

The surgical literature is paying more and more attention to the topic of soft or non-technical skills (NTS), defined as those cognitive and social skills that characterize high-performing individuals and teams. NTS are essential in supporting surgeons in dealing with unexpected situations. During the COVID-19 pandemic, NTS have been considered crucial in defining situation awareness, enhancing decision making, communicating among groups and teams, and fostering leadership. With a "looking back and planning forward" approach, the current perspective aims at deepening the contribution of NTS for surgeons to deal with the unexpected challenges posed by the COVID crisis, surgical emergencies, the introduction of new technologies in clinical practice, to understand how such skills may help shape the surgical leaders of the future.

7.
Surg Endosc ; 36(1): 826-832, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34741202

RESUMO

BACKGROUND: Laparoscopic endoscopic cooperative colorectal surgery (LECS-CR) is a promising technique to achieve full-thickness resection of colorectal tumors. This approach has shown good rates of complete resection and low local recurrence, especially for large laterally spreading tumors, which are difficult to remove via endoscopy alone. However, it is often difficult to prevent peritoneal leakage of intestinal content, causing infections and risks of cancer spreading. It was hypothesized that a robotic assistance could make the procedure easier and decrease intestinal fluid leakage. This preclinical trial aims to assess the feasibility of robotic and endoscopic cooperative colorectal surgery (RECS-CR). METHODS: LECS-CR was performed in five female pigs and RECS-CR was also performed in five female pigs. With the animal under general anesthesia, pseudotumors were created on the colonic mucosa at a distance comprised between 20 and 25 cm from the anal verge. Desired resection margins were marked endoscopically and two stay sutures were placed either robotically or laparoscopically. A mucosa-to-submucosa dissection was performed endoscopically along the markings. Complete full-thickness dissection was performed cooperatively. The specimen was withdrawn endoscopically. The colon was closed using a self-fixating running suture. Abdominal contaminations, operating times, complications, and complete resections were evaluated and compared between LECS-CR and RECS-CR. RESULTS: The mean number of colonies of Escherichia coli in the RECS group was significantly lower than in the LECS group (36.7 ± 30.2 vs. 142.2 ± 78.4, respectively, p < 0.05). Operating time was comparable (118 ± 11.2 vs. 98.6 ± 25.7, respectively, p = 0.22). Two stenoses occurred in the LECS group. R0 resection was achieved in all cases. CONCLUSION: This study suggests that RECS-CR is feasible and has the potential to reduce intestinal content leakage, potentially preventing postoperative infections.


Assuntos
Neoplasias Colorretais , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Animais , Neoplasias Colorretais/cirurgia , Estudos de Viabilidade , Feminino , Laparoscopia/métodos , Suínos , Resultado do Tratamento
8.
J Hepatobiliary Pancreat Sci ; 29(1): 16-32, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34779150

RESUMO

BACKGROUND: The concept of minimally invasive anatomic liver resection (MIALR) is gaining popularity. However, specific technical skills need to be acquired to safely perform MIALR. The "Expert Consensus Meeting: Precision Anatomy for Minimally Invasive HBP Surgery (PAM-HBP Surgery Consensus)" was developed as a special program during the 32nd meeting of the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS). METHODS: Thirty-four international experts gathered online for the consensus. A Research Committee performed a comprehensive literature review, classifying studies according to the Scottish Intercollegiate Guidelines Network method. Based on the literature review and experts' opinions, tentative recommendations were drafted and circulated among experts using online Delphi Rounds. Finally, formulated recommendations were presented online in the Expert Consensus Meeting of the JSHBPS on February 23rd, 2021. The final recommendations were validated and finalized by the 2nd Delphi Round in May 2021. RESULTS: Seven clinical questions were selected, and 22 recommendations were formulated. All recommendations reached more than 85% consensus among experts at the final Delphi Round. CONCLUSIONS: The Expert Consensus Meeting for safely performing MIALR has presented a set of clinical guidelines based on available literature and experts' opinions. We expect these guidelines to have a favorable effect on the safe implementation and development of MIALR.


Assuntos
Hepatectomia , Procedimentos Cirúrgicos Minimamente Invasivos , Consenso , Humanos , Fígado/cirurgia
9.
J Hepatobiliary Pancreat Sci ; 29(1): 66-81, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33475254

RESUMO

PURPOSE: In this systematic review, we aimed to clarify the useful anatomic structures and assess available surgical techniques and strategies required to safely perform minimally invasive anatomic liver resection (MIALR), with a particular focus on the hepatic veins (HVs). METHODS: A systematic review was conducted using MEDLINE/PubMed for English articles and Ichushi databases for Japanese articles through September 2020. The quality assessment of the articles was performed in accordance with the Scottish Intercollegiate Guidelines Network (SIGN). RESULTS: A total of 3372 studies were obtained, and 59 were selected and reviewed. Due to the limited number of published comparative studies and case series, the degree of evidence from our review was low. Thirty-two articles examined the anatomic landmarks and crucial structures for approaching HVs. Regarding the direction of HV exposure, 32 articles focused on the techniques and advantages of exposing HVs from either the root or the periphery. Ten articles focused on the techniques to perform a segmentectomy 8 in particularly difficult cases of MIALR. In seven articles, bleeding control from HVs was also discussed. CONCLUSIONS: This review may help experts reach a consensus regarding the best approach to the management of hepatic veins during MIALR.


Assuntos
Hepatectomia , Veias Hepáticas , Veias Hepáticas/cirurgia , Humanos , Fígado/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos
10.
J Hepatobiliary Pancreat Sci ; 29(1): 33-40, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34866343

RESUMO

BACKGROUND: Although the number of minimally invasive liver resections (MILRs) has been steadily increasing in many institutions, minimally invasive anatomic liver resection (MIALR) remains a complicated procedure that has not been standardized. We present the results of a survey among expert liver surgeons as a benchmark for standardizing MIALR. METHOD: We administered this survey to 34 expert liver surgeons who routinely perform MIALR. The survey contained questions on personal experience with liver resection, inflow/outflow control methods, and identification techniques of intersegmental/sectional planes (IPs). RESULTS: All 34 participants completed the survey; 24 experts (70%) had more than 11 years of experience with MILR, and over 80% of experts had performed over 100 open resections and MILRs each. Regarding the methods used for laparoscopic or robotic anatomic resection, the Glissonean approach (GA) was a more frequent procedure than the hilar approach (HA). Although hepatic veins were considered essential landmarks, the exposure methods varied. The top three techniques that the experts recommended for identifying IPs were creating a demarcation line, indocyanine green negative staining method, and intraoperative ultrasound. CONCLUSION: Minimally invasive anatomic liver resection remains a challenging procedure; however, a certain degree of consensus exists among expert liver surgeons.


Assuntos
Laparoscopia , Neoplasias Hepáticas , Hepatectomia , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Inquéritos e Questionários
11.
J Hepatobiliary Pancreat Sci ; 29(1): 6-15, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34866349

RESUMO

BACKGROUND: The Brisbane 2000 Terminology for Liver Anatomy and Resections, based on Couinaud's segments, did not address how to identify segmental borders and anatomic territories of less than one segment. Smaller anatomic resections including segmentectomies and subsegmentectomies, have not been well defined. The advent of minimally invasive liver resection has enhanced the possibilities of more precise resection due to a magnified view and reduced bleeding, and minimally invasive anatomic liver resection (MIALR) is becoming popular gradually. Therefore, there is a need for updating the Brisbane 2000 system, including anatomic segmentectomy or less. An online "Expert Consensus Meeting: Precision Anatomy for Minimally Invasive HBP Surgery (PAM-HBP Surgery Consensus)" was hosted on February 23, 2021. METHODS: The Steering Committee invited 34 international experts from around the world. The Expert Committee (EC) selected 12 questions and two future research topics in the terminology session. The EC created seven tentative definitions and five recommendations based on the experts' opinions and the literature review performed by the Research Committee. Two Delphi Rounds finalized those definitions and recommendations. RESULTS: This paper presents seven definitions and five recommendations regarding anatomic segmentectomy or less. In addition, two future research topics are discussed. CONCLUSIONS: The PAM-HBP Surgery Consensus has presented the Tokyo 2020 Terminology for Liver Anatomy and Resections. The terminology has added definitions of liver anatomy and resections that were not defined in the Brisbane 2000 system.


Assuntos
Hepatectomia , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos , Tóquio
12.
Molecules ; 26(19)2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34641286

RESUMO

Hepatocellular carcinoma (HCC) is the most common form of liver cancer. The number of cases is increasing and the trend for the next few years is not encouraging. HCC is usually detected in the advanced stages of the disease, and pharmacological therapies are not entirely effective. For this reason, it is necessary to search for new therapeutic options. The objective of this work was to evaluate the effect of the drugs isotretinoin and thalidomide on c-MYC expression and cancer-related proteins in an HCC cellular model. The expression of c-MYC was measured using RT-qPCR and western blot assays. In addition, luciferase activity assays were performed for the c-MYC promoters P1 and P2 using recombinant plasmids. Dose-response-time analyses were performed for isotretinoin or thalidomide in cells transfected with the c-MYC promoters. Finally, a proteome profile analysis of cells exposed to these two drugs was performed and the results were validated by western blot. We demonstrated that in HepG2 cells, isotretinoin and thalidomide reduced c-MYC mRNA expression levels, but this decrease in expression was linked to the regulation of P1 and P1-P2 c-MYC promoter activity in isotretinoin only. Thalidomide did not exert any effect on c-MYC promoters. Also, isotretinoin and thalidomide were capable of inducing and repressing proteins associated with cancer. In conclusion, isotretinoin and thalidomide down-regulate c-MYC mRNA expression and this is partially due to P1 or P2 promoter activity, suggesting that these drugs could be promising options for modulating the expression of oncogenes and tumor suppressor genes in HCC.


Assuntos
Carcinoma Hepatocelular/metabolismo , Isotretinoína/farmacologia , Neoplasias Hepáticas/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Talidomida/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Regiões Promotoras Genéticas , Proteômica/métodos
13.
Toxicol Appl Pharmacol ; 433: 115774, 2021 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-34699867

RESUMO

Supplements containing pharmacological concentrations of biotin are commercially available. The mechanisms by which biotin at pharmacological concentrations exerts its action have been the subject of multiple investigations, particularly for biotin's medicinal potential and wide use for cosmetic purposes. Several studies have reported that biotin supplementation increases cell proliferation; however, the mechanisms involved in this effect have not yet been characterized. In a previous study, we found that a biotin-supplemented diet increased spermatogonia proliferation. The present study was focused on investigating the molecular mechanisms involved in biotin-induced testis cell proliferation. Male BALB/cAnNHsd mice were fed a control or a biotin-supplemented diet (1.76 or 97.7 mg biotin/kg diet) for eight weeks. Compared with the control group, the biotin-supplemented mice presented augmented protein abundance of the c-kit-receptor and pERK1/2Tyr204 and pAKTSer473, the active forms of ERK/AKT proliferation signaling pathways. No changes were observed in the testis expression of the stem cell factor and in the serum levels of the follicle-stimulating hormone. Analysis of mRNA abundance found an increase in cyclins Ccnd3, Ccne1, Ccna2; Kinases Cdk4, Cdk2; and E2F; and Sp1 & Sp3 transcription factors. Decreased expression of cyclin-dependent kinase inhibitor 1a (p21) was observed but not of Cdkn2a inhibitor (p16). The results of the present study identifies, for the first time, the mechanisms associated with biotin supplementation-induced cell proliferation, which raises concerns about the effects of biotin on male reproductive health because of its capacity to cause hyperplasia, especially because this vitamin is available in large amounts without regulation.


Assuntos
Biotina/toxicidade , Proliferação de Células/efeitos dos fármacos , Suplementos Nutricionais/toxicidade , Hormônio Foliculoestimulante/sangue , Espermatogônias/efeitos dos fármacos , Fator de Células-Tronco/metabolismo , Testículo/efeitos dos fármacos , Animais , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-kit/genética , Proteínas Proto-Oncogênicas c-kit/metabolismo , Transdução de Sinais , Fator de Transcrição Sp1/genética , Fator de Transcrição Sp1/metabolismo , Fator de Transcrição Sp3/genética , Fator de Transcrição Sp3/metabolismo , Espermatogônias/metabolismo , Espermatogônias/patologia , Testículo/metabolismo , Testículo/patologia
14.
J Laparoendosc Adv Surg Tech A ; 31(10): 1097-1103, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34171972

RESUMO

Background: Image-guided liver surgery and interventions are growing as part of the current trend to translate liver procedures into minimally invasive approaches. Hands-on surgical training in such techniques is required. Consequently, a meaningful and realistic liver tumor model using multi-imaging modalities, such as ultrasound (US), computed tomography (CT), magnetic resonance (MR), cone beam-CT (CBCT), is mandatory. The first aim of this study is to develop a novel tumor-mimic model and assess it with multi-imaging modalities. The second aim is to evaluate the usefulness of the model during image-guided liver procedures. Materials and Methods: The tumor-mimic model is made of a composition of hydrogel, smashed muscle, and gadolinium contrast solution. Five ex vivo livers and three pigs were included in the study. Procedures were performed in an experimental hybrid operating room. Under general anesthesia, US guidance was required to inject the biotumor formula into the pig's liver. US, CT, CBCT, and MR acquisitions were then performed after the initial injection. In vivo models were then used to perform liver procedures, including US-guided biopsy, radiofrequency ablation, and laparoscopic resection. Results: The formula developed is easily injected generating a tissue-like material. Visualization using multi-imaging modalities was appropriate, thereby allowing to perform image-guided techniques. Conclusion: A novel design of an in vivo and ex vivo tissue-like tumor liver model is presented. Due to the multimodality imaging appraisal, it may provide a realistic and meaningful model allowing to perform image-guided liver procedures.


Assuntos
Neoplasias Hepáticas , Cirurgia Assistida por Computador , Animais , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos , Suínos , Tomografia Computadorizada por Raios X , Ultrassonografia
15.
Molecules ; 26(7)2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33805347

RESUMO

A generation of induced pluripotent stem cells (iPSC) by ectopic expression of OCT4, SOX2, KLF4, and c-MYC has established promising opportunities for stem cell research, drug discovery, and disease modeling. While this forced genetic expression represents an advantage, there will always be an issue with genomic instability and transient pluripotency genes reactivation that might preclude their clinical application. During the reprogramming process, a somatic cell must undergo several epigenetic modifications to induce groups of genes capable of reactivating the endogenous pluripotency core. Here, looking to increase the reprograming efficiency in somatic cells, we evaluated the effect of epigenetic molecules 5-aza-2'-deoxycytidine (5AZ) and valproic acid (VPA) and two small molecules reported as reprogramming enhancers, CHIR99021 and A83-01, on the expression of pluripotency genes and the methylation profile of the OCT4 promoter in a human dermal fibroblasts cell strain. The addition of this cocktail to culture medium increased the expression of OCT4, SOX2, and KLF4 expression by 2.1-fold, 8.5-fold, and 2-fold, respectively, with respect to controls; concomitantly, a reduction in methylated CpG sites in OCT4 promoter region was observed. The epigenetic cocktail also induced the expression of the metastasis-associated gene S100A4. However, the epigenetic cocktail did not induce the morphological changes characteristic of the reprogramming process. In summary, 5AZ, VPA, CHIR99021, and A83-01 induced the expression of OCT4 and SOX2, two critical genes for iPSC. Future studies will allow us to precise the mechanisms by which these compounds exert their reprogramming effects.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Decitabina/farmacologia , Fibroblastos/efeitos dos fármacos , Pirazóis/farmacologia , Piridinas/farmacologia , Pirimidinas/farmacologia , Tiossemicarbazonas/farmacologia , Ácido Valproico/farmacologia , Linhagem Celular , Epigênese Genética/efeitos dos fármacos , Fibroblastos/citologia , Expressão Gênica/efeitos dos fármacos , Humanos , Fator 4 Semelhante a Kruppel
16.
BMC Gastroenterol ; 21(1): 24, 2021 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-33422010

RESUMO

BACKGROUND: An intravascular ultrasound catheter (IVUSc) was developed for intracardiac ultrasound to assess interventions with compelling results. However, intrahepatic vascular exploration was rarely tested and was always associated with X-ray techniques. The aim of this study was to demonstrate the feasibility to navigate through the whole liver using an IVUSc, providing high-quality images and making it unnecessary to use ionizing radiation. METHODS: An ex vivo pig visceral block and an in vivo pig model were used in this study. The IVUS equipment was composed of an US system, and of an 8 French lateral firing IVUSc capable of producing 90-degree sector images in the longitudinal plane. After accessing the intravascular space with the IVUSc into the models, predetermined anatomical landmarks were visualized from the inferior vena cava and hepatic veins and corroborated. RESULTS: IVUS navigation was achieved in both models successfully. The entire navigation protocol took 87 and 48 min respectively, and 100% (21/21) and 96.15% (25/26) of the landmarks were correctly identified with the IVUSc alone in the ex vivo and in vivo models respectively. IVUS allowed to clearly visualize the vasculature beyond third-order branches of the hepatic and portal veins. CONCLUSIONS: A complete IVUS liver navigation is feasible using the IVUSc alone, making it unnecessary to use ionizing radiation. This approach provides high-definition and real-time images of the complex liver structure and offers a great potential for future clinical applications during diagnostic and therapeutic interventions.


Assuntos
Veia Porta , Ultrassonografia de Intervenção , Animais , Fígado/diagnóstico por imagem , Cintilografia , Suínos , Ultrassonografia
17.
Surg Endosc ; 35(12): 6724-6730, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33398561

RESUMO

BACKGROUND AND AIMS: Percutaneous cholangioscopy (PC) is more complex and invasive than a transpapillary approach, with the need for a large percutaneous tract of 16 French (Fr) on average in order to advance standard percutaneous cholangioscopes. The aim of this study was to investigate whether percutaneous single-operator cholangioscopy (pSOC) using the SpyGlass™ DS system is feasible, safe, and effective in PC for diagnostic and therapeutic indications. MATERIALS AND METHODS: The data of 28 patients who underwent pSOC in 4 tertiary referral centers were retrospectively analyzed. Technical and clinical success for therapeutic procedures was assessed as well as diagnostic accuracy of pSOC-guided biopsies and visualization. Adverse events and the required number and size of dilatations were reviewed. RESULTS: 25/28 (89%) patients had a post-surgical altered anatomy. The average number of percutaneous dilatations prior to pSOC was 1.25 with a mean dilatation size of 11 French. Histopathology showed a 100% accuracy. Visual impression showed an overall accuracy of 96.4%. Technical and clinical success was achieved in 27/28 (96%) of cases. Adverse events occurred in 3/28 (10.7%) cases. CONCLUSION: pSOC is a feasible, safe, and effective technique for diagnostic and therapeutic indications. It may be considered an alternative approach in clinical cases where gastrointestinal anatomy is altered. It has the potential to reduce peri-procedural adverse events and costs. Prospective randomized-controlled trials are necessary to confirm the previously collected data.


Assuntos
Procedimentos Cirúrgicos do Sistema Biliar , Laparoscopia , Cateterismo , Endoscopia do Sistema Digestório , Humanos , Estudos Prospectivos , Estudos Retrospectivos
18.
J Laparoendosc Adv Surg Tech A ; 31(7): 790-795, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32991240

RESUMO

Background: Malignant or benign biliary obstructions can be successfully managed with minimally invasive percutaneous interventions. Since percutaneous approaches are challenging, extensive training using relevant models is fundamental to improve the proficiency of percutaneous physicians. The aim of this experimental study was to develop an in vivo training model in pigs to simulate bile duct dilatation to be used during percutaneous biliary interventions. Materials and Methods: Twenty-eight large white pigs were involved and procedures were performed in an experimental hybrid operating room. Under general anesthesia, animals underwent a preoperative magnetic resonance cholangiography (MRC). Afterward, the common bile duct was isolated and ligated laparoscopically. A postoperative MRC was performed 72 hours after the procedure to evaluate bile duct dilatation. The In vivo models presenting an effective dilatation model were included in the hands-on part of a percutaneous surgery training course. Animals were euthanized at the end of the training session. Results: Postoperative MRC confirmed the presence of bile duct dilatation in the survival pigs (n = 25). No intraoperative complications occurred and mean operative time was 15.8 ± 5.27 minutes. During the course, 27 trainees could effectively perform percutaneous transhepatic cholangiography, bile duct drainage, biliary duct dilatation, and stent placement, with a > 90% success rate, thereby validating the experimental model. All animals survived during the training procedures and complications occurred in 28.3% of cases. Conclusion: The creation of an in vivo bile duct dilatation animal model is feasible with a low short-term mortality. It provides a realistic and meaningful training model in percutaneous biliary procedures.


Assuntos
Procedimentos Cirúrgicos do Sistema Biliar/educação , Colestase/cirurgia , Laparoscopia/educação , Modelos Animais , Cirurgia Assistida por Computador/educação , Animais , Ductos Biliares/cirurgia , Procedimentos Cirúrgicos do Sistema Biliar/métodos , Colangiografia , Colestase/etiologia , Dilatação/métodos , Estudos de Viabilidade , Humanos , Laparoscopia/métodos , Masculino , Cirurgia Assistida por Computador/métodos , Suínos
19.
J Laparoendosc Adv Surg Tech A ; 30(9): 993-997, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32628558

RESUMO

The current unprecedented coronavirus 2019 (COVID-19) crisis has accelerated and enhanced e-learning solutions. During the so-called transition phase, efforts were made to reorganize surgical services, reschedule elective surgical procedures, surgical research, academic education, and careers to optimize results. The intention to switch to e-learning medical education is not a new concern. However, the current crisis triggered an alarm to accelerate the transition. Efforts to consider e-learning as a teaching and training method for medical education have proven to be efficient. For image-guided therapies, the challenge requires more effort since surgical skills training is combined with image interpretation training, thus the challenge is to cover quality educational content with a balanced combination of blended courses (online/onsite). Several e-resources are currently available in the surgical scenario; however, further efforts to enhance the current system are required by accelerating the creation of new learning solutions to optimize complex surgical education needs in the current disrupted environment.


Assuntos
Instrução por Computador/tendências , Infecções por Coronavirus/epidemiologia , Educação a Distância/tendências , Educação Médica/tendências , Cirurgia Geral/educação , Pneumonia Viral/epidemiologia , Betacoronavirus , COVID-19 , França , Humanos , Internet , Aprendizagem , Pandemias , SARS-CoV-2
20.
Ann Surg Open ; 1(2): e021, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33392607

RESUMO

OBJECTIVE: To develop consensus definitions of image-guided surgery, computer-assisted surgery, hybrid operating room, and surgical navigation systems. SUMMARY BACKGROUND DATA: The use of minimally invasive procedures has increased tremendously over the past 2 decades, but terminology related to image-guided minimally invasive procedures has not been standardized, which is a barrier to clear communication. METHODS: Experts in image-guided techniques and specialized engineers were invited to engage in a systematic process to develop consensus definitions of the key terms listed above. The process was designed following review of common consensus-development methodologies and included participation in 4 online surveys and a post-surveys face-to-face panel meeting held in Strasbourg, France. RESULTS: The experts settled on the terms computer-assisted surgery and intervention, image-guided surgery and intervention, hybrid operating room, and guidance systems and agreed-upon definitions of these terms, with rates of consensus of more than 80% for each term. The methodology used proved to be a compelling strategy to overcome the current difficulties related to data growth rates and technological convergence in this field. CONCLUSIONS: Our multidisciplinary collaborative approach resulted in consensus definitions that may improve communication, knowledge transfer, collaboration, and research in the rapidly changing field of image-guided minimally invasive techniques.

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