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1.
Surg Endosc ; 38(1): 66-74, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37903884

RESUMO

BACKGROUND: The use of the laparoscopic approach for the treatment of carcinomatosis from epithelial ovarian cancer (EOC) is controversial. The aim of this study was to compare the short-term outcomes of both laparoscopic and open approach for interval CRS+HIPEC in a matched cohort of patients with advanced EOC. METHODS: A retrospective analysis of a prospectively maintained database including 254 patients treated with interval CRS-HIPEC between January 2016 and December 2021 was performed. Patients with primary disease and limited carcinomatosis (PCI ≤ 10) were selected. A comparative analysis of patients treated by either open (O-CRS-HIPEC) or the laparoscopic (L-CRS-HIPEC) approach was conducted. Overall survival (OS), disease-free survival (DFS), and perioperative outcomes were analysed. RESULTS: Fifty-three patients were finally selected and enrolled into two comparable groups in this study. Of these, 14 patients were treated by interval L-CRS-HIPEC and 39 by interval O-CRS-HIPEC. The L-CRS-HIPEC group had a shorter hospital stay (5.6 ± 1.9 vs. 9.7 ± 9.8 days; p < 0.001) and a shorter time to return to systemic chemotherapy (4.3 ± 1.9 vs. 10.3 ± 16.8 weeks; p = 0.003). There were no significant differences in postoperative complications between both groups. The 2-year OS and DFS was 100% and 62% in the L-CRS-HIPEC group versus 92% and 60% in the O-CRS-HIPEC group, respectively (p = 0.96; p = 0.786). CONCLUSION: This study suggests that the use of interval L-CRS-HIPEC for primary advanced EOC is associated with shorter hospital stay and return to systemic treatment while obtaining similar oncological results compared to the open approach. Further prospective research is needed to recommend this new approach for these strictly selected patients.


Assuntos
Carcinoma , Hipertermia Induzida , Laparoscopia , Neoplasias Ovarianas , Intervenção Coronária Percutânea , Neoplasias Peritoneais , Humanos , Feminino , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/cirurgia , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Peritoneais/tratamento farmacológico , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Procedimentos Cirúrgicos de Citorredução/métodos , Hipertermia Induzida/métodos , Carcinoma/cirurgia , Neoplasias Ovarianas/cirurgia , Terapia Combinada , Taxa de Sobrevida
2.
Int J Environ Health Res ; : 1-12, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38817088

RESUMO

Parents´ perceptions can influence their children´s mode of commuting to school. In this sense, the purposes of this study were to compare parental barriers towards active commuting to school (ACS) between Ecuadorian and Spanish children, and to analyze the associations between those barriers and the children's mode of commuting. Descriptive and comparative analyses were performed using Chi-square and T-student test. Associations were analyzed by several logistic regression models. Results showed that road safety is the main barrier for ACS, and that all the barriers are perceived as higher by Ecuadorian parents (p<0.001). It was also found that Ecuadorian children were less likely to be active when parents perceive greater total barriers (OR=0.15, CI=0.06, 0.40). Public policies should focus on reducing the parental barriers in order to increase ACS, specifically those related to road safety.

3.
Haematologica ; 108(1): 110-121, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-35770532

RESUMO

Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are CD19-targeted chimeric antigen receptor (CAR) T cells approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). We performed a retrospective study to evaluate safety and efficacy of axi-cel and tisa-cel outside the setting of a clinical trial. Data from consecutive patients with R/R LBCL who underwent apheresis for axi-cel or tisa-cel were retrospectively collected from 12 Spanish centers. A total of 307 patients underwent apheresis for axi-cel (n=152) and tisa-cel (n=155) from November 2018 to August 2021, of which 261 (85%) received a CAR T infusion (88% and 82%, respectively). Median time from apheresis to infusion was 41 days for axi-cel and 52 days for tisa-cel (P=0.006). None of the baseline characteristics were significantly different between both cohorts. Both cytokine release syndrome and neurologic events (NE) were more frequent in the axi-cel group (88% vs. 73%, P=0.003, and 42% vs. 16%, P<0.001, respectively). Infections in the first 6 months post-infusion were also more common in patients treated with axi-cel (38% vs. 25%, P=0.033). Non-relapse mortality was not significantly different between the axi-cel and tisa-cel groups (7% and 4%, respectively, P=0.298). With a median follow-up of 9.2 months, median PFS and OS were 5.9 and 3 months, and 13.9 and 11.2 months for axi-cel and tisa-cel, respectively. The 12-month PFS and OS for axi-cel and tisa-cel were 41% and 33% (P=0.195), 51% and 47% (P=0.191), respectively. Factors associated with lower OS in the multivariate analysis were increased lactate dehydrogenase, ECOG ≥2 and progressive disease before lymphodepletion. Safety and efficacy results in our real-world experience were comparable with those reported in the pivotal trials. Patients treated with axi-cel experienced more toxicity but similar non-relapse mortality compared with those receiving tisa-cel. Efficacy was not significantly different between both products.


Assuntos
Imunoterapia Adotiva , Linfoma Difuso de Grandes Células B , Humanos , Proteínas Adaptadoras de Transdução de Sinal , Antígenos CD19 , Imunoterapia Adotiva/efeitos adversos , Linfoma Difuso de Grandes Células B/terapia , Estudos Retrospectivos
4.
Pharmacol Res ; 187: 106578, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36435271

RESUMO

BACKGROUND AND AIMS: Metformin, the most prescribed drug for the treatment of type 2 diabetes mellitus, has been recently reported to promote weight loss by upregulating the anorectic cytokine growth differentiation factor 15 (GDF15). Since the antidiabetic effects of metformin are mostly mediated by the activation of AMPK, a key metabolic sensor in energy homeostasis, we examined whether the activation of this kinase by metformin was dependent on GDF15. METHODS: Cultured hepatocytes and myotubes, and wild-type and Gdf15-/- mice were utilized in a series of studies to investigate the involvement of GDF15 in the activation of AMPK by metformin. RESULTS: A low dose of metformin increased GDF15 levels without significantly reducing body weight or food intake, but it ameliorated glucose intolerance and activated AMPK in the liver and skeletal muscle of wild-type mice but not Gdf15-/- mice fed a high-fat diet. Cultured hepatocytes and myotubes treated with metformin showed AMPK-mediated increases in GDF15 levels independently of its central receptor GFRAL, while Gdf15 knockdown blunted the effect of metformin on AMPK activation, suggesting that AMPK is required for the metformin-mediated increase in GDF15, which in turn is needed to sustain the full activation of this kinase independently of the CNS. CONCLUSION: Overall, these findings uncover a novel mechanism through which GDF15 upregulation by metformin is involved in achieving and sustaining full AMPK activation by this drug independently of the CNS.


Assuntos
Proteínas Quinases Ativadas por AMP , Diabetes Mellitus Tipo 2 , Fator 15 de Diferenciação de Crescimento , Hipoglicemiantes , Metformina , Animais , Camundongos , Proteínas Quinases Ativadas por AMP/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Fator 15 de Diferenciação de Crescimento/genética , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Metformina/farmacologia , Metformina/uso terapêutico , Retroalimentação Fisiológica
5.
Langenbecks Arch Surg ; 408(1): 146, 2023 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-37046100

RESUMO

PURPOSE: The benefits of the minimally invasive approach for performing cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (L-CRS + HIPEC) have been described previously, associating an early recovery with similar oncologic outcomes in patients with limited peritoneal carcinomatosis. Currently, no studies are focusing on the learning curve for this emerging procedure. This study aimed to evaluate the L-CRS + HIPEC learning curve and its knock-on effect on the perioperative outcomes. METHODS: We identified all consecutive unselected patients who underwent L-CRS + HIPEC by a single surgeon between April 2016 and January 2022 (n = 51). Patients who underwent risk-reducing CRS + HIPEC (PCI = 0) or initial conversion due to an intraoperative PCI > 10 were excluded from the final analysis. To evaluate the learning curve, perioperative data were analysed using the cumulative sum (CUSUM) analysis. RESULTS: Twenty-six patients were included in the final analysis. Major morbidity occurred in one patient (3.8%). The difficulty of the L-CRS + HIPEC procedures was categorised as low in 23.1% (n = 6), intermediate in 19.2% (n = 5), and advanced in 57.7% (n = 15). The mean length of hospital stay was 5.4 ± 1.5 days. No patient had a conversion to open surgery. The learning curve was divided into two distinct phases: the learning phase (1-14) and the consolidation phase (15-26). A significant decrease in the operative time (375 ± 103.1 vs 239.2 ± 63.6 min) was observed with no differences in complexity, the number of peritonectomy procedures, or morbidity. CONCLUSION: L-CRS + HIPEC is a complex procedure that must be performed in a high-volume and experienced oncologic unit, requiring a learning curve to achieve the consolidation condition, which could be established after 14 procedures.


Assuntos
Hipertermia Induzida , Intervenção Coronária Percutânea , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Curva de Aprendizado , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos Retrospectivos , Terapia Combinada , Taxa de Sobrevida
6.
Rev Esp Enferm Dig ; 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37930001

RESUMO

We report the case of a 91-year-old female with acute cholangitis and long-standing symptoms of recurrent colic- related abdominal pain after cholecystectomy. She was diagnosed by abdominal CT of saccular dilation of the intramural bile duct in the duodenum suggesting choledococele. ERCP was performed in which the presumptive diagnosis was confirmed, and choledochotomy and choledochoplasty were done with excellent subsequent progress. Choledococele is the least common type of biliary cyst. It consists of a cystic dilation of the intramural portion of the common bile duct that protrudes into the duodenal lumen and causes symptoms of recurrent abdominal pain and biliary events. ERCP is a key test in both diagnosis and treatment except when they cannot be approached by this technique or malignancy is suspected.

7.
J Struct Biol ; 214(4): 107907, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36272694

RESUMO

Backbone dihedral angles ϕ and ψ are the main structural descriptors of proteins and peptides. The distribution of these angles has been investigated over decades as they are essential for the validation and refinement of experimental measurements, as well as for structure prediction and design methods. The dependence of these distributions, not only on the nature of each amino acid but also on that of the closest neighbors, has been the subject of numerous studies. Although neighbor-dependent distributions are nowadays generally accepted as a good model, there is still some controversy about the combined effects of left and right neighbors. We have investigated this question using rigorous methods based on recently-developed statistical techniques. Our results unambiguously demonstrate that the influence of left and right neighbors cannot be considered independently. Consequently, three-residue fragments should be considered as the minimal building blocks to investigate polypeptide sequence-structure relationships.


Assuntos
Peptídeos
8.
J Biol Chem ; 297(1): 100854, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34097875

RESUMO

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease. Variants in MYBPC3, the gene encoding cardiac myosin-binding protein C (cMyBP-C), are the leading cause of HCM. However, the pathogenicity status of hundreds of MYBPC3 variants found in patients remains unknown, as a consequence of our incomplete understanding of the pathomechanisms triggered by HCM-causing variants. Here, we examined 44 nontruncating MYBPC3 variants that we classified as HCM-linked or nonpathogenic according to cosegregation and population genetics criteria. We found that around half of the HCM-linked variants showed alterations in RNA splicing or protein stability, both of which can lead to cMyBP-C haploinsufficiency. These protein haploinsufficiency drivers associated with HCM pathogenicity with 100% and 94% specificity, respectively. Furthermore, we uncovered that 11% of nontruncating MYBPC3 variants currently classified as of uncertain significance in ClinVar induced one of these molecular phenotypes. Our strategy, which can be applied to other conditions induced by protein loss of function, supports the idea that cMyBP-C haploinsufficiency is a fundamental pathomechanism in HCM.


Assuntos
Cardiomiopatia Hipertrófica/genética , Proteínas de Transporte/genética , Haploinsuficiência/genética , Splicing de RNA/genética , Cardiomiopatia Hipertrófica/patologia , Proteínas de Transporte/química , Proteínas de Transporte/ultraestrutura , Proteínas do Citoesqueleto/química , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/ultraestrutura , Feminino , Humanos , Masculino , Simulação de Dinâmica Molecular , Mutação/genética , Fenótipo
9.
Ann Surg Oncol ; 29(1): 126-136, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34215955

RESUMO

BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare malignancy, classified according to the Peritoneal Surface Oncology Group International (PSOGI) classification, whose response to treatment remains highly heterogeneous within the high-grade (HG) category. Molecular profiling of PMP cases might help to better categorize patients and predict treatment responses. METHODS: We studied the Ki-67 proliferation rate and P53 overexpression in tissue samples from our historical cohort of HG-PMP patients. We established as cut-off levels the third quartile of each marker to perform univariate and multivariate Cox regression survival analyses. According to these results, the HG-PMP category was divided into subcategories and a new survival analysis was performed. RESULTS: A total of 90/117 patients with PMP undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) were selected for secondary analysis. The survival analysis of the HG-PMP category for preoperative variables showed that a proliferation index defined by Ki-67 >15% is a bad prognostic factor, with a hazard ratio (HR) of 3.20 (95% confidence interval [CI] 1.24-8.25). Accordingly, the HG-PMP group was divided using the Ki-67 15% cut-off. The new PSOGI/Ki-67 variable was an independent prognostic factor for overall survival (OS), with an HR of 3.74 (95% CI 1.88-7.47), and disease-free survival (DFS), with an HR of 4.184 (95% CI 1.79-9.75). The estimated 5-year OS rate was 100%, 70% and 24% for the LG-PMP, HG-PMP ≤15% and HG-PMP >15% groups, respectively (p = 0.0001), while the 5-year DFS rate was 90%, 44% and 0%, respectively (p = 0.0001). CONCLUSION: Division of the HG-PMP category of the PSOGI classification, according to the Ki-67 proliferation index, provides two well-defined subcategories, with significant differences in terms of OS and DFS, and hence high prognostic value.


Assuntos
Neoplasias Peritoneais , Pseudomixoma Peritoneal , Proliferação de Células , Humanos , Antígeno Ki-67 , Neoplasias Peritoneais/terapia , Pseudomixoma Peritoneal/terapia
10.
FASEB J ; 35(10): e21911, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34551152

RESUMO

Pleiotrophin is a pleiotropic cytokine that has been demonstrated to have a critical role in regulating energy metabolism, lipid turnover and plasticity of adipose tissue. Here, we hypothesize that this cytokine can be involved in regulatory processes of glucose and lipid homeostasis in the liver during pregnancy. Using 18-days pregnant Ptn-deficient mice, we evaluated the biochemical profile (circulating variables), tissue mRNA expression (qPCR) and protein levels of key enzymes and transcription factors involved in main metabolic pathways. Ptn deletion was associated with a reduction in body weight gain, hyperglycemia and glucose intolerance. Moreover, we observed an impairment in glucose synthesis and degradation during late pregnancy in Ptn-/- mice. Hepatic lipid content was significantly lower (73.6%) in Ptn-/- mice and was associated with a clear reduction in fatty acid, triacylglycerides and cholesterol synthesis. Ptn deletion was accompanying with a diabetogenic state in the mother and a decreased expression of key proteins involved in glucose and lipid uptake and metabolism. Moreover, Ptn-/- pregnant mice have a decreased expression of transcription factors, such as PPAR-α, regulating lipid uptake and glucose and lipid utilization. Furthermore, the augmented expression and nuclear translocation of glycerol kinase, and the decrease in NUR77 protein levels in the knock-out animals can further explain the alterations observed in hepatic glucose metabolism. Our results point out for the first time that pleiotrophin is an important player in maintaining hepatic metabolic homeostasis during late gestation, and further highlighted the moonlighting role of glycerol kinase in the regulation of maternal glucose homeostasis during pregnancy.


Assuntos
Proteínas de Transporte/genética , Citocinas/deficiência , Citocinas/genética , Deleção de Genes , Intolerância à Glucose/genética , Glicerol Quinase/metabolismo , Metabolismo dos Lipídeos , Fígado/metabolismo , Animais , Colesterol/metabolismo , Ácidos Graxos/metabolismo , Feminino , Glucose/biossíntese , Glucose/metabolismo , Lipoproteínas/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Camundongos , Gravidez , Fatores de Transcrição/metabolismo , Triglicerídeos/metabolismo , Aumento de Peso/genética
11.
Cell Commun Signal ; 20(1): 53, 2022 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-35428325

RESUMO

BACKGROUND: Peroxisome proliferator-activated receptor γ (PPARγ) coactivator 1α (PGC-1α) downregulation in skeletal muscle contributes to insulin resistance and type 2 diabetes mellitus. Here, we examined the effects of endoplasmic reticulum (ER) stress on PGC-1α levels in muscle and the potential mechanisms involved. METHODS: The human skeletal muscle cell line LHCN-M2 and mice exposed to different inducers of ER stress were used. RESULTS: Palmitate- or tunicamycin-induced ER stress resulted in PGC-1α downregulation and enhanced expression of activating transcription factor 4 (ATF4) in human myotubes and mouse skeletal muscle. Overexpression of ATF4 decreased basal PCG-1α expression, whereas ATF4 knockdown abrogated the reduction of PCG-1α caused by tunicamycin in myotubes. ER stress induction also activated mammalian target of rapamycin (mTOR) in myotubes and reduced the nuclear levels of cAMP response element-binding protein (CREB)-regulated transcription co-activator 2 (CRTC2), a positive modulator of PGC-1α transcription. The mTOR inhibitor torin 1 restored PCG-1α and CRTC2 protein levels. Moreover, siRNA against S6 kinase, an mTORC1 downstream target, prevented the reduction in the expression of CRTC2 and PGC-1α caused by the ER stressor tunicamycin. CONCLUSIONS: Collectively, these findings demonstrate that ATF4 and the mTOR-CRTC2 axis regulates PGC-1α transcription under ER stress conditions in skeletal muscle, suggesting that its inhibition might be a therapeutic target for insulin resistant states. Video Abstract.


Assuntos
Fator 4 Ativador da Transcrição , Diabetes Mellitus Tipo 2 , Estresse do Retículo Endoplasmático , Músculo Esquelético , Serina-Treonina Quinases TOR , Fatores de Transcrição , Fator 4 Ativador da Transcrição/metabolismo , Animais , Diabetes Mellitus Tipo 2/metabolismo , Regulação para Baixo , Camundongos , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Fatores de Transcrição/metabolismo , Tunicamicina/metabolismo , Tunicamicina/farmacologia
12.
Nucleic Acids Res ; 48(17): e102, 2020 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-32813015

RESUMO

Transposon sequencing is commonly applied for identifying the minimal set of genes required for cellular life; a major challenge in fields such as evolutionary or synthetic biology. However, the scientific community has no standards at the level of processing, treatment, curation and analysis of this kind data. In addition, we lack knowledge about artifactual signals and the requirements a dataset has to satisfy to allow accurate prediction. Here, we have developed FASTQINS, a pipeline for the detection of transposon insertions, and ANUBIS, a library of functions to evaluate and correct deviating factors known and uncharacterized until now. ANUBIS implements previously defined essentiality estimate models in addition to new approaches with advantages like not requiring a training set of genes to predict general essentiality. To highlight the applicability of these tools, and provide a set of recommendations on how to analyze transposon sequencing data, we performed a comprehensive study on artifacts corrections and essentiality estimation at a 1.5-bp resolution, in the genome-reduced bacterium Mycoplasma pneumoniae. We envision FASTQINS and ANUBIS to aid in the analysis of Tn-seq procedures and lead to the development of accurate genome essentiality estimates to guide applications such as designing live vaccines or growth optimization.


Assuntos
Elementos de DNA Transponíveis , Genômica/métodos , Análise de Sequência de DNA/métodos , Software , Genômica/normas , Mycoplasma pneumoniae , Recombinação Genética , Análise de Sequência de DNA/normas
13.
HPB (Oxford) ; 24(6): 933-941, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34815189

RESUMO

BACKGROUND: Surgical resection is a first-line curative option for hepatocellular carcinoma, but its role is still unclear in elderly patients. The aim of our study was to compare short- and long-term outcomes of laparoscopic and open liver resection in elderly patients with hepatocellular carcinoma. METHODS: The study included 665 consecutive hepatocellular carcinoma liver resection cases in patients with ≥70 years of age treated in eight European hospital centres. Patients were divided into laparoscopic and open liver resection groups. Perioperative and long-term outcomes were compared between these groups. RESULTS: After a 1:1 propensity score matching, 219 patients were included in each group. Clavien-Dindo grades III/IV (6 vs. 20%, p = 0.04) were lower in the laparoscopic than in the open matched group. Hospital stay was shorter in the laparoscopic than in the open matched group (5 vs. 7 days, p < 0.001). There were no significant differences between laparoscopic and open groups regarding overall survival and disease-free survival at 1-, 3- and 5- year periods. CONCLUSION: Laparoscopic liver resection for hepatocellular carcinoma is associated with good short-term outcomes in patients with ≥70 years of age compared to open liver resection. Laparoscopic liver resection is safe and feasible in elderly patients with hepatocellular carcinoma.


Assuntos
Carcinoma Hepatocelular , Laparoscopia , Neoplasias Hepáticas , Idoso , Carcinoma Hepatocelular/patologia , Hepatectomia/efeitos adversos , Humanos , Laparoscopia/efeitos adversos , Tempo de Internação , Neoplasias Hepáticas/patologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Pontuação de Propensão , Estudos Retrospectivos , Resultado do Tratamento
14.
Bioinformatics ; 36(14): 4208-4210, 2020 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-32437555

RESUMO

SUMMARY: Accurate 3D modelling of protein-protein interactions (PPI) is essential to compensate for the absence of experimentally determined complex structures. Here, we present a new set of commands within the ModelX toolsuite capable of generating atomic-level protein complexes suitable for interface design. Among these commands, the new tool ProteinFishing proposes known and/or putative alternative 3D PPI for a given protein complex. The algorithm exploits backbone compatibility of protein fragments to generate mutually exclusive protein interfaces that are quickly evaluated with a knowledge-based statistical force field. Using interleukin-10-R2 co-crystalized with interferon-lambda-3, and a database of X-ray structures containing interleukin-10, this algorithm was able to generate interleukin-10-R2/interleukin-10 structural models in agreement with experimental data. AVAILABILITY AND IMPLEMENTATION: ProteinFishing is a portable command-line tool included in the ModelX toolsuite, written in C++, that makes use of an SQL (tested for MySQL and MariaDB) relational database delivered with a template SQL dump called FishXDB. FishXDB contains the empty tables of ModelX fragments and the data used by the embedded statistical force field. ProteinFishing is compiled for Linux-64bit, MacOS-64bit and Windows-32bit operating systems. This software is a proprietary license and is distributed as an executable with its correspondent database dumps. It can be downloaded publicly at http://modelx.crg.es/. Licenses are freely available for academic users after registration on the website and are available under commercial license for for-profit organizations or companies. CONTACT: javier.delgado@crg.eu or luis.serrano@crg.eu. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Algoritmos , Software , Proteínas
15.
Ann Surg Oncol ; 28(5): 2819-2827, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33471266

RESUMO

BACKGROUND: Several classifications have been used for pseudomyxoma peritonei (PMP), and among these, the Ronnett classification is the most commonly used. However, a new consensual Peritoneal Surface Oncology Group International (PSOGI) classification has recently been proposed. Nonetheless, to date, the ability of the PSOGI classification to predict survival based on its different disease histologic categories has not been validated. METHODS: This study enrolled 117 patients with PMP who had undergone cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) between 1997 and 2020. Cox proportional hazards regression models and time-dependent curve receiver operating characteristic (ROC) analyses were used to assess the predictive capacity of both classification systems for the overall survival (OS) and disease-free survival (DFS) of these patients. RESULTS: Significant differences in the 5-year OS rate were found for the different histologic grades according to each of the classifications. The completeness of cytoreduction score (CCS) was identified as a factor that predicted patient OS prognosis (p = 0.006). According to the time-dependent ROC curves at the "100" time point, adjusted by the CCS and DFS, the capacity to predict OS was optimal and achieved an area under the curve (AUC) of about 69% for OS and approximately 62% for DFS. CONCLUSIONS: Both the Ronnett and PSOGI classifications were able to predict survival optimally for this patient cohort. However, when the classifications were adjusted by the CCS, the predictive availability for OS was better with the PSOGI classification than with the Ronnett classification.


Assuntos
Hipertermia Induzida , Neoplasias Peritoneais , Pseudomixoma Peritoneal , Procedimentos Cirúrgicos de Citorredução , Humanos , Neoplasias Peritoneais/terapia , Modelos de Riscos Proporcionais , Pseudomixoma Peritoneal/cirurgia , Estudos Retrospectivos
16.
Surg Endosc ; 35(7): 3642-3652, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-32748269

RESUMO

BACKGROUND: Considering the increase in overall life expectancy and the rising incidence of hepatocellular carcinoma (HCC), more elderly patients are considered for hepatic resection. Traditionally, major hepatectomy has not been proposed to the elderly due to severe comorbidities. Indeed, only a few case series are reported in the literature. The present study aimed to compare short-term and long-term outcomes between laparoscopic major hepatectomy (LMH) and open major hepatectomy (OMH) in elderly patients with HCC using propensity score matching (PSM). METHODS: We performed a multicentric retrospective study including 184 consecutive cases of HCC major liver resection in patients aged ≥ 70 years in _8 European Hospital Centers. Patients were divided into LMH and OMH groups, and perioperative and long-term outcomes were compared between the 2 groups. RESULTS: After propensity score matching, 122 patients were enrolled, 38 in the LMH group and 84 in the OMH group. Postoperative overall complications were lower in the LMH than in the OMH group (18 vs. 46%, p < 0.001). Hospital stay was shorter in the LMH group than in the OMH group (5 vs. 7 days, p = 0.01). Mortality at 90 days was comparable between the two groups. There were no significant differences between the two groups in terms of overall survival (OS) and disease-free survival (DFS) at 1, 3, and 5 years. CONCLUSION: LMH for HCC is associated with appropriate short-term outcomes in patients aged ≥ 70 years as compared to OMH. LMH is safe and feasible in elderly patients with HCC.


Assuntos
Carcinoma Hepatocelular , Laparoscopia , Neoplasias Hepáticas , Idoso , Carcinoma Hepatocelular/cirurgia , Hepatectomia/efeitos adversos , Humanos , Tempo de Internação , Neoplasias Hepáticas/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Pontuação de Propensão , Estudos Retrospectivos , Resultado do Tratamento
17.
Int J Mol Sci ; 22(11)2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34071721

RESUMO

Changes in lifestyle in developed countries have triggered the prevalence of obesity and type 2 diabetes mellitus (T2DM) in the latest years. Consequently, these metabolic diseases associated to insulin resistance, and the morbidity associated with them, accounts for enormous costs for the health systems. The best way to face this problem is to identify potential therapeutic targets and/or early biomarkers to help in the treatment and in the early detection. In the insulin receptor signaling cascade, the activities of protein tyrosine kinases and phosphatases are coordinated, thus, protein tyrosine kinases amplify the insulin signaling response, whereas phosphatases are required for the regulation of the rate and duration of that response. The focus of this review is to summarize the impact of transmembrane receptor protein tyrosine phosphatase (RPTPs) in the insulin signaling cascade and secretion, and their implication in metabolic diseases such as obesity and T2DM.


Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Insulina/metabolismo , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/metabolismo , Animais , Humanos , Resistência à Insulina , Obesidade , Prevalência , Proteínas Tirosina Fosfatases/metabolismo , Receptor de Insulina/metabolismo , Transdução de Sinais/fisiologia
18.
HPB (Oxford) ; 23(9): 1311-1320, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34090805

RESUMO

BACKGROUND: The aim of this systematic review is to evaluate the current evidence in the context of clinical prediction model for post-hepatectomy liver failure (PHLF). METHODS: A systematic search of the English literature for a period from December 2005 to September 2020 was conducted. Primary outcome was defined using the three common PHLF criteria (50-50 criteria, peak bilirubin>7 mg/dl criteria, and ≥ grade B PHLF criteria by the International Study Group of Liver Surgery). Studies that reported the value of area under receiver operative characteristic curve (AUC) for the occurrence of PHLF were included. RESULTS: Twenty eight of 1327 screened articles were eligible for inclusion. Eighteen studies developed the prediction models. The median AUC was found to be 0.79 (0.65-0.933). The parameters related to the amount of future liver remnant volume were most commonly identified as significant predictors for PHLF in statistical analysis (24 studies) and were most frequently incorporated in the prediction models (18 studies). The parameters associated with portal hypertension were significant for predicting PHLF in 16 studies and were adopted in the prediction models in 14 studies. CONCLUSION: Parameters related to future liver remnant volume and portal hypertension seem to be facilitating in predicting PHLF.


Assuntos
Carcinoma Hepatocelular , Falência Hepática , Neoplasias Hepáticas , Carcinoma Hepatocelular/cirurgia , Hepatectomia/efeitos adversos , Humanos , Falência Hepática/diagnóstico , Falência Hepática/etiologia , Neoplasias Hepáticas/cirurgia , Modelos Estatísticos , Complicações Pós-Operatórias/etiologia , Prognóstico , Estudos Retrospectivos
19.
Int J Dent Hyg ; 19(2): 209-214, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33001564

RESUMO

OBJECTIVES: To compare clinical efficacy for plaque removal between dental floss with soft ellipsoidal knots and conventional floss. MATERIALS AND METHODS: We studied 33 university students (29 females and 4 males, 13 of them undergraduate/postgraduate students of dentistry), including regular and sporadic (less once/wk) users of dental floss, with interproximal spaces ≤1 mm, who used floss with and without knots in a randomized manner following a split-mouth design. The Modified Navy Plaque Index (RMNPI) by Rustogi et al. was applied to determine the total removed plaque (TPI) and that removed in the gingival area (GPI) and interproximal spaces (IPI). RESULTS: The reduction in GPI was greater with the knotted vs conventional floss in all cases (14.77 ± 12.38; 64.79% vs 17.38 ± 13.66; 57.51%) and especially among no floss users (12.469 ± 10.98; 68.02% vs 15.833 ± 11.88; 58.55%). No statistically significant difference between floss types was found in TPI and IPI (globally or by floss utilization frequency) or in the mean GPI of floss users. CONCLUSION: Floss with ellipsoidal knots showed similar efficacy to remove plaque in patients with less experience of flossing (but without statistically significant differences) compared with flossing themselves with conventional floss, and it may be an optimal solution for patients starting to use dental floss and for those with a lesser or only sporadic history of floss utilization.


Assuntos
Placa Dentária , Gengivite , Dispositivos para o Cuidado Bucal Domiciliar , Placa Dentária/prevenção & controle , Índice de Placa Dentária , Feminino , Humanos , Masculino , Escovação Dentária
20.
Eur J Orthop Surg Traumatol ; 31(8): 1657-1662, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34677661

RESUMO

PURPOSE: Several preoperation prognosis models used on the treatment of metastatic bone disease on appendicular skeleton have been devised. The purpose of this study was to compare the performance of different survival prognostic models on patients with metastatic bone disease in long bones in a Chilean population. METHODS: This is a multicentric retrospective study. We retrospectively reviewed the medical records of 136 patients who were confirmed with metastatic bone disease of the appendicular skeleton and who were treated surgically from 2016 to 2019. The minimum follow-up time was 12 months. All patients were assessed using four appendicular metastatic bone disease scoring systems. A preoperative predicted survival time for all 136 patients was retrospectively calculated making use of the revised Katagiri, PathFx, Optimodel and IOR score model. RESULTS: The PathFx model demonstrated an accuracy at predicting 3 (area under the curve [AUC] = 0.61) and 6-month (AUC = 0.65) survival time after surgical management. IOR score model demonstrated an accuracy at predicting 12-month survival time (AUC = 0.64). The survival rate reached the 44% in a year. The median survival time to death or last follow-up time was 14.9 months (SD ± 15). CONCLUSION: PathFx score model demonstrated the highest accuracy at predicting a survival time of 3 and 6 months. IOR score model was the most accurate measure at predicting a survival time of 12-months. To our knowledge, this is the first study reporting a comparative analysis of metastatic bone disease with predicting models in a country located in Latin America. PathFx's and IOR score models are the ones to be used in the Chilean population as the predictive models in metastatic bone disease of the appendicular skeleton.


Assuntos
Neoplasias Ósseas , Área Sob a Curva , Osso e Ossos , Humanos , Prognóstico , Estudos Retrospectivos
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