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1.
Genet Mol Biol ; 46(3 Suppl 1): e20230133, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38252059

RESUMEN

The TP53 3'UTR variant rs78378222 A>C has been detected in different tumor types as a somatic alteration that reduces p53 expression through modification of polyadenylation and miRNA regulation. Its prevalence is not yet known in all tumors. Herein, we examine tumor tissue prevalence of rs7837822 in Brazilian cohorts of patients from south and southeast regions diagnosed with lung adenocarcinoma (LUAD, n=586), sarcoma (SARC, n=188) and uterine leiomyoma (ULM, n=41). The minor allele (C) was identified in heterozygosity in 6/586 LUAD tumors (prevalence = 1.02 %) and none of the SARC and ULM samples. Additionally, next generation sequencing analysis revealed that all variant-positive tumors (n=4) with sample availability had additional pathogenic or likely pathogenic somatic variants in the TP53 coding regions. Among them, 3/4 (75 %) had the same pathogenic or likely pathogenic sequence variant (allele frequency <0.05 in tumor DNA) namely c.751A>C (p.Ile251Leu). Our results indicate a low somatic prevalence of rs78378222 in LUAD, ULM and SARC tumors from Brazilian patients, which suggests that no further analysis of this variant in the specific studied regions of Brazil is warranted. However, these findings should not exclude tumor molecular testing of this TP53 3'UTR functional variant for different populations.

2.
Eur J Orthop Surg Traumatol ; 33(3): 571-580, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36094673

RESUMEN

INTRODUCTION: The standard treatment of anterior glenaoid fractures carrying > 20% of the glenoid fossa is open reduction and internal fixation (ORIF). In the herein study, we report our outcomes in a retrospective cohort of anterior and anteroinferior glenoid rim fractures using an accelerated postoperative rehabilitation protocol. A secondary aim is to describe the surgical steps for ORIF of anterior and anteroinferior glenoid rim fractures using the anterior axillary approach, describing the tricks, pearls, and pitfalls of this surgical technique. METHODS: A retrospective cohort of skeletally mature patients treated for an anterior glenoid rim fracture carrying > 20% of the glenoid fossa during a 10-year period were operated on using a vertical axillary incision, osteosynthesis with 2.0-mm cortical screws, and labral repair with small diameter metallic anchors and non-absorbable sutures. Rehabilitation began on the first postoperative day, including passive external rotation exercises and active-assisted flexion, adduction, and abduction exercises as tolerated. The exercises are performed with the patient sitting or lying down. Phase 1 is continued for 6-10 weeks until the patient regains painless, normal, or near-normal ROM. Usually by 10 weeks, the fracture and labrum are healed, so phase 2 rehabilitation begins with strengthening and ROM exercises. Radiologic and clinical outcomes, including active range of motion (ROM), glenohumeral stability, and visual analogue scale (VAS) were measured. RESULTS: About 33 patients (35 fractures) had complete medical records and pre- and post-operative imaging exams available for further analysis regarding the surgical protocol, with a mean of 4.8 years. The mean DASH questionnaire was 3.75 ± 9.0 and the mean CM score was 62.5 ± 0.1. Active flexion and internal rotation were recovered in all patients, while external rotation presented an average loss of 8° (p = 0.12) and abduction of 5° (p = 0.33). The mean VAS was 1.1 ± 0.8. No patient reported major or disabling symptoms, or great difficulty or inability to perform daily or recreational activities. No patient presented residual instability of the glenohumeral joint. CONCLUSION: In this retrospective cohort, ORIF using a vertical axillary incision, osteosynthesis with 2.0-mm screws, and labral repair with small diameter metallic anchors and non-absorbable sutures was a safe approach, with a minimal risk of complications and residual instability. The accelerated postoperative rehabilitation protocol, allowing immediate passive external rotation of the operated shoulder, resulted in a non-significant loss of ROM compared to the contralateral side. Therefore, we recommend this management strategy for anterior glenoid rim fractures in patients with unstable shoulder joint after traumatic glenohumeral dislocation. LEVEL OF EVIDENCE IV: Therapeutic Study (Surgical technique and Retrospective cohort).


Asunto(s)
Fracturas Óseas , Inestabilidad de la Articulación , Luxación del Hombro , Articulación del Hombro , Humanos , Estudios Retrospectivos , Escápula/cirugía , Fracturas Óseas/cirugía , Fracturas Óseas/complicaciones , Fijación Interna de Fracturas/efectos adversos , Fijación Interna de Fracturas/métodos , Articulación del Hombro/cirugía , Luxación del Hombro/cirugía , Inestabilidad de la Articulación/etiología , Rango del Movimiento Articular , Artroscopía/métodos , Resultado del Tratamiento
3.
J Sci Food Agric ; 102(9): 3665-3672, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34893984

RESUMEN

BACKGROUND: We evaluated different machine learning (ML) models for predicting soybean productivity up to 1 month in advance for the Matopiba agricultural frontier (States of Maranhão, Tocantins, Piauí, and Bahia). We collected meteorological data on the NASA-POWER platform and soybean yield on the SIDRA/IBGE base between 2008 and 2017. The ML models evaluated were random forest (RF), artificial neural networks, radial base support vector machines (SVM_RBF), linear model and polynomial regression. To assess the performance of the models, cross-validation was used, obtaining the value of precision by R2 , accuracy by root mean square error (RMSE), and trend by the mean error of the estimate (EME). RESULTS: The results showed that the RF algorithm achieves the highest precision and accuracy, with R2 of 0.81, RMSE of 176.93 kg ha-1 and trend (EME) of 1.99 kg ha-1 . On the other hand, the SVM_RBF algorithm showed the lowest performance, with R2 of 0.74, RMSE of 213.58 kg ha-1 and EME of -15.06 kg ha-1 . The average yield values predicted by the models were within the expected range for the region, which has a historical average value of 2.730 kg ha-1 . CONCLUSION: All models had acceptable precision, accuracy and trend indices, which makes it possible to use all algorithms to be applied in the prediction of soybean crop yield, observing the particularities of the region to be studied, in addition to being a useful tool for agricultural planning and decision making in soy-producing regions such as the Brazilian Cerrado. © 2021 Society of Chemical Industry.


Asunto(s)
Fabaceae , Glycine max , Algoritmos , Brasil , Aprendizaje Automático , Máquina de Vectores de Soporte
4.
Clin Psychol Psychother ; 29(3): 1080-1088, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-34806246

RESUMEN

The aim of this paper is to analyse the factors associated with the dropout from brief psychotherapy for adults with major depressive disorder (MDD) treated at a mental health outpatient clinic. This is a randomized clinical trial with two models of psychotherapy: cognitive behavioural therapy (CBT) and supportive expressive dynamic psychotherapy (SEDP). MDD and anxiety disorders were evaluated through the Mini International Neuropsychiatric Interview-Plus. The personality disorders were evaluated by the Millon Clinical Multiaxial Inventory-III. The severity of depressive symptoms was measured using the Beck Depression Inventory-II and resilience through Resilience Scale. Of the 215 participants, 41.9% abandoned psychotherapy (n = 90), and, of these, 54.4% (n = 49) abandoned after the fourth session. The proportion of psychotherapy dropout was higher among those with nonwhite skin colour, belonging to economic classes C and D, who had children and whose depressive symptoms were moderate. Presence of obsessive-compulsive personality trait was protective against dropout. The damage caused by this abrupt interruption is evident for all those involved in the psychotherapeutic process, so the clinician should pay attention to the predictors found in this study in order to develop strategies that promote therapeutic adherence.


Asunto(s)
Terapia Cognitivo-Conductual , Trastorno Depresivo Mayor , Psicoterapia Breve , Adulto , Trastornos de Ansiedad/complicaciones , Trastornos de Ansiedad/psicología , Trastornos de Ansiedad/terapia , Niño , Trastorno Depresivo Mayor/psicología , Trastorno Depresivo Mayor/terapia , Humanos , Psicoterapia , Resultado del Tratamiento
5.
Oncology ; 94(6): 383-393, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29539615

RESUMEN

OBJECTIVE: Ewing sarcoma (ES) is a type of childhood cancer probably arising from stem mesenchymal or neural crest cells. The epidermal growth factor receptor (EGFR) acts as a driver oncogene in many types of solid tumors. However, its involvement in ES remains poorly understood. METHODS: Human SK-ES-1 and RD-ES ES cells were treated with EGF, the EGFR inhibitor tyrphostin (AG1478), or phosphoinositide 3-kinase (PI3K) or extracellular-regulated kinase (ERK)/mitogen-activated kinase (MAPK) inhibitors. Cell proliferation survival, cycle, and senescence were analyzed. The protein content of possible targets of EGFR manipulation was measured by Western blot. RESULTS: Cell proliferation and survival were increased by EGF and inhibited by AG1478. The EGFR inhibitor also altered the cell cycle, inducing arrest in G1 and increasing the sub-G1 population, reduced polyploidy and increased the population of senescent cells. In addition, AG1478 reduced the levels of phosphorylated AKT (p-AKT), ERK, p-ERK, cyclin D1, and brain-derived neurotrophic factor (BDNF), while enhancing p53 levels. Cell proliferation was also impaired by inhibitors of PI3K or ERK, alone or combined with AG1478. CONCLUSIONS: Our findings reveal novel aspects of EGFR regulation of ES cells and provide early evidence for antitumor activities of EGFR inhibitors in ES.


Asunto(s)
Neoplasias Óseas/patología , Proliferación Celular/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Receptores ErbB/metabolismo , Quinazolinas/farmacología , Sarcoma de Ewing/patología , Tirfostinos/farmacología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Línea Celular Tumoral , Ciclina D1/metabolismo , Factor de Crecimiento Epidérmico/farmacología , Receptores ErbB/antagonistas & inhibidores , Quinasas MAP Reguladas por Señal Extracelular/antagonistas & inhibidores , Puntos de Control de la Fase G1 del Ciclo Celular/efectos de los fármacos , Humanos , Inhibidores de las Quinasa Fosfoinosítidos-3 , Fosforilación/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Proteína p53 Supresora de Tumor/metabolismo
6.
Transplant Proc ; 56(5): 1092-1095, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38744591

RESUMEN

BACKGROUND: Hepatic artery pseudoaneurysm after liver transplantation is a rare condition that can lead to spontaneous bleeding, depending on its extent and location. Treatment involves endovascular and surgical approaches in addition to liver retransplantation in cases of graft failure. CASE REPORT: A 42-year-old female underwent deceased donor liver transplantation due to cryptogenic cirrhosis and schistosomiasis with an uneventful postoperative course. However, 18 days after the operation, she presented to the emergency department with abdominal pain, hypotension, and lipothymia. A computed tomography scan revealed a hepatic artery anastomotic pseudoaneurysm, and due to hemodynamic instability, emergency laparotomy was indicated. During the operation, the pseudoaneurysm was found to be ruptured, and the recipient's hepatic artery was ligated due to life-threatening bleeding. She later developed ischemic cholangiopathy and biliary complications, eventually undergoing retransplantation 7 months after the emergency operation. The patient remains well 11 months after the retransplantation. CONCLUSION: We report a rare case of life-threatening rupture of hepatic artery pseudoaneurysm, which required emergency ligation of the recipient's hepatic artery and subsequent liver retransplantation due to biliary complications.


Asunto(s)
Aneurisma Falso , Aneurisma Roto , Arteria Hepática , Trasplante de Hígado , Humanos , Trasplante de Hígado/efectos adversos , Aneurisma Falso/cirugía , Aneurisma Falso/etiología , Femenino , Arteria Hepática/cirugía , Arteria Hepática/diagnóstico por imagen , Adulto , Aneurisma Roto/cirugía , Aneurisma Roto/etiología , Reoperación , Complicaciones Posoperatorias/cirugía , Complicaciones Posoperatorias/etiología , Tomografía Computarizada por Rayos X
7.
Transplant Proc ; 56(5): 1087-1091, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38862365

RESUMEN

BACKGROUND: Liver adenomatosis is characterized by multiple adenomas diffusely distributed throughout the liver parenchyma. Studies addressing liver transplantation for those cases are scarce, and the criteria used to indicate transplantation are still debatable. OBJECTIVE: To report a single-center experience of liver transplantation for diffuse adenomatosis. METHODS: Single-center retrospective study involving all adult patients who underwent liver transplantation due to adenomatosis from January/2010 to June/2023. RESULTS: A total of 13 patients were identified, corresponding to 0.89% of liver transplants performed during the study period. The mean age was 33 ± 6.55 years, and most of them were female (n = 9, 69.23%). There were 12 transplants with deceased donors and 1 with a right lobe from a living donor. The most frequent reason to preclude liver resection was multiple and large unresectable adenomas in patients without previous liver disease (n = 8, 61.58%), followed by underlying liver disease (Abernethy Malformation, n = 3, 23.07%) and recurrence after liver resection (n = 2, 15.38%). The indications for liver transplantation were high risk of malignant transformation (n = 7, 53.84%), increasing size and number of nodules (n = 3, 23.07%), confirmed malignant transformation (n = 2, 15.38%), and hemorrhage (n = 2, 15.38%). There was 1 perioperative death due to primary non-function. Another patient died during follow-up because of COVID-19. CONCLUSION: Liver adenomatosis is a rare indication for liver transplantation, with acceptable post-transplant outcomes. Unresectable adenomas with high-risk or confirmed malignant transformation are the main indications for transplant. Reasons for unresectability involve underlying liver disease, multiple and large high-risk nodules, and recurrence after previous resection.


Asunto(s)
Neoplasias Hepáticas , Trasplante de Hígado , Humanos , Femenino , Estudios Retrospectivos , Adulto , Masculino , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , Adenoma/cirugía , Adenoma/patología , Persona de Mediana Edad , Resultado del Tratamiento , Adulto Joven
8.
Gene ; 898: 148069, 2024 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-38070788

RESUMEN

PURPOSE: Li-Fraumeni Syndrome (LFS) is a rare cancer predisposing condition caused by germline pathogenic TP53 variants, in which core tumors comprise sarcomas, breast, brain and adrenocortical neoplasms. Clinical manifestations are highly variable in carriers of the Brazilian germline founder variant TP53 p.R337H, possibly due to the influence of modifier genes such as miRNA genes involved in the regulation of the p53 pathway. Herein, we investigated the potential phenotypic effects of two miRNA-related functional SNPs, pri-miR-34b/c rs4938723 and 3'UTR KRAS rs61764370, in a cohort of 273 LFS patients from Southern and Southeastern Brazil. METHODS: The genotyping of selected SNPs was performed by TaqMan® allelic discrimination and subsequently custom TaqMan® genotyping results were confirmed by Sanger sequencing in all SNP-positive LFS patients. RESULTS: Although the KRAS SNP showed no effect as a phenotype modulator, the rs4938723 CC genotype was significantly associated with development of LFS non-core tumors (first tumor diagnosis) in p.R337H carriers (p = 0.039). Non-core tumors were also more frequently diagnosed in carriers of germline TP53 DNA binding domain variants harboring the rs4938723 C variant allele. Previous studies described pri-miR-34b/c rs4938723 C as a risk allele for sporadic occurrence of thyroid and prostate cancers (non-core tumors of the LFS spectrum). CONCLUSION: With this study, we presented additional evidence about the importance of analyzing miRNA genes that could indirectly regulate p53 expression, and, therefore, may modulate the LFS phenotype, such as those of the miR-34 family.


Asunto(s)
Síndrome de Li-Fraumeni , MicroARNs , Masculino , Humanos , Síndrome de Li-Fraumeni/genética , Síndrome de Li-Fraumeni/epidemiología , Proteína p53 Supresora de Tumor/genética , Regiones no Traducidas 3'/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Polimorfismo de Nucleótido Simple , Predisposición Genética a la Enfermedad , MicroARNs/genética , Mutación de Línea Germinal , Fenotipo
9.
Transplant Proc ; 56(5): 1104-1109, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-39048477

RESUMEN

BACKGROUND: Simultaneous liver-kidney transplantation is indicated for patients with concomitant end-stage liver disease and end-stage renal disease. The traditional technique involves separate implantations of the liver and the kidney. In the en bloc approach, the liver is recovered en bloc with the right kidney and the donor renal artery is anastomosed to the donor splenic artery. We aimed to compare the outcomes of the traditional and en bloc techniques for simultaneous liver-kidney transplantation in a single center. METHODS: This single-center retrospective study involved all adult patients who underwent simultaneous liver-kidney transplantation from brain-dead donors from January 2017 to December 2022. RESULTS: A total of 15 patients were included: 10 transplanted with the traditional technique and 5 with the en bloc approach. Patients in the en bloc group presented higher body mass index, shorter kidney cold and total ischemia times, shorter overall surgical time and longer kidney warm ischemia time (29.07 kg/m2vs 23.20 kg/m2 [P = .048]; 560 minutes vs 880 minutes [P = .026]; 615 minutes vs 908 minutes [P = 0.025]; 405 minutes vs 485 minutes [P = .046]; 46 minutes vs 33.5 minutes [P = 0.027], respectively). Ureteroneocystostomy was performed in 2 patients of the en bloc group and ureteroureterostomy in the remaining 3 patients. One patient in the en bloc group presented stenosis of renal artery anastomosis and underwent percutaneous angioplasty. This same patient eventually developed late urinary fistula. In the traditional technique group, there were 2 cases of renal vein thrombosis and 1 of ureteral stenosis. CONCLUSIONS: Compared with the traditional technique, the en bloc approach is feasible and safe, reducing kidney total ischemia time and overall surgical time.


Asunto(s)
Trasplante de Riñón , Trasplante de Hígado , Humanos , Trasplante de Riñón/métodos , Trasplante de Hígado/métodos , Estudios Retrospectivos , Femenino , Masculino , Persona de Mediana Edad , Adulto , Resultado del Tratamiento , Fallo Renal Crónico/cirugía , Enfermedad Hepática en Estado Terminal/cirugía , Tempo Operativo , Isquemia Tibia , Arteria Renal/cirugía
10.
Transplant Proc ; 56(5): 1098-1103, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38862363

RESUMEN

INTRODUCTION: Polycystic liver disease and giant hepatic hemangioma may present with severe symptom burden and indicate orthotopic liver transplantation. The left-to-right piggyback approach is a useful technique for performing total hepatectomy of enlarged livers. OBJECTIVE: The purpose of this study is to analyze the results of liver transplantation in patients with benign massive hepatomegaly. METHODS: This is a single-center retrospective study involving all adult patients who underwent liver transplantation due to benign massive hepatomegaly from January 2002 to June 2023. RESULTS: A total of 22 patients underwent liver transplantation (21 cases of polycystic live disease and 1 case of giant hepatic hemangioma). During the same time, there were 2075 transplants; therefore, benign massive hepatomegaly accounted for 1.06% of cases. Most patients (59.09%) were transplanted using the left-to-right piggyback technique. Seven patients had previous attempted treatment of hepatic cysts. Another patient previously underwent bilateral nephrectomy and living-donor kidney transplantation. Among these patients, in 5 cases there were massive abdominal adhesions with increased bleeding. Four of these 8 patients died in the very early perioperative period. In comparison to patients without previous cysts manipulation, massive adhesions and perioperative death were significantly higher in those cases (62.5 vs 0%, P = .002 and 50% vs 0%, P = .004, respectively). CONCLUSION: Liver transplantation due to polycystic liver disease and giant hemangioma is a rare event. Total hepatectomy is challenging due to the enlarged native liver. The left-to-right piggyback technique is useful, because it avoids vena cava twisting and avulsion of its branches. Massive adhesions due to previous cysts manipulation may lead to increased bleeding, being a risk factor for mortality.


Asunto(s)
Quistes , Hepatomegalia , Hepatopatías , Trasplante de Hígado , Humanos , Estudios Retrospectivos , Masculino , Hepatomegalia/cirugía , Hepatomegalia/etiología , Femenino , Adulto , Persona de Mediana Edad , Quistes/cirugía , Hepatopatías/cirugía , Hemangioma/cirugía , Hepatectomía/métodos , Resultado del Tratamiento , Neoplasias Hepáticas/cirugía
11.
Transplant Proc ; 56(5): 1080-1082, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38862364

RESUMEN

BACKGROUND: Hepatic artery thrombosis is the most common vascular complication of liver transplantation. When occurring late in the postoperative course, it may have no clinical repercussions, and conservative treatment may be implemented. Some patients, however, will develop severe biliary complications due to ischemic cholangiopathy and require retransplantation. The aim of this study is to report the outcomes of retransplantation in this population. METHODS: This is a single-center retrospective study involving all adult patients who underwent liver retransplantation due to late hepatic artery thrombosis from January/2010 to December/2022. RESULTS: During the study period, 1378 liver transplants were performed in our center; 147 were retransplantations, with 13 cases of late hepatic artery thrombosis (0.94%). All had symptomatic ischemic cholangiopathy. Twelve of them had already presented previous cholangitis, bilomas, or liver abscesses and had undergone biliary stenting or percutaneous drainage. The median time between the first liver transplant and late hepatic artery thrombosis diagnosis and between this diagnosis and retransplantation were 73 and 50 days, respectively. Arterial reconstruction using splenic artery, celiac trunk, or arterial conduit from the aorta was performed in 7 cases, whereas biliary reconstruction was mostly done with choledochojejunostomy (n = 8). There were 4 perioperative deaths, 2 due to primary non-function and 2 due to refractory shock after exceedingly complex retransplants. CONCLUSION: Liver retransplantation due to late hepatic artery thrombosis is a rare condition that should be offered to patients who develop severe biliary complications and recurrent infections. It is nonetheless a challenging procedure associated with significant perioperative mortality.


Asunto(s)
Arteria Hepática , Trasplante de Hígado , Reoperación , Trombosis , Humanos , Arteria Hepática/cirugía , Trasplante de Hígado/efectos adversos , Trombosis/etiología , Trombosis/cirugía , Estudios Retrospectivos , Masculino , Persona de Mediana Edad , Femenino , Adulto , Complicaciones Posoperatorias/cirugía , Resultado del Tratamiento , Anciano
12.
AMB Express ; 13(1): 131, 2023 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-37989852

RESUMEN

The methylotrophic yeast Komagataella phaffii is one of the most important microbial platforms to produce recombinant proteins. Despite its importance in the context of industrial biotechnology, the use of synthetic biology approaches in K. phaffii is hampered by the fact that few genetic tools are available for precise control of gene expression in this system. In this work, we used an RNA aptamer activated by tetracycline to modulate protein production at the translational level. Using lacZ as gene reporter, we have demonstrated significant reduction of the heterologous protein upon addition of tetracycline. Furthermore, this genetic control device was applied for the control of Ku70p. This protein is involved in non-homologous recombination and the control of its production paves the way for the development of strains exhibiting higher rates of homologous recombination.

13.
J Affect Disord ; 330: 291-299, 2023 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-36871912

RESUMEN

OBJECTIVE: To evaluate the effect of psychotherapies on ego defense mechanisms and the reduction of depressive symptoms in a 12-month follow-up period. METHODS: This longitudinal and quasi-experimental study nested within a randomized clinical trial included a clinical sample of adults (18-60 years) diagnosed with major depressive disorder using the Mini-International Neuropsychiatric Interview. Two models of psychotherapy were used: Supportive Expressive Dynamic Psychotherapy (SEDP) and Cognitive Behavioral Therapy (CBT). Defense Style Questionnaire 40 was used to analyze defense mechanisms and the Beck Depression Inventory was used to measure the depressive symptoms. RESULTS: The total sample comprised 195 patients (113 SEDP and 82 CBT), with the mean age was 35.63 (11.44) years. After adjustments, increased mature defenses was significantly associated with reduced depressive symptoms at all follow-up times (p < 0.001) and the decrease in immature defenses was significantly associated with the reduction of depressive symptoms at all follow-up times (p < 0.001). While neurotic defenses were not associated with a reduction in depressive symptoms at any time of follow-up (p > 0.05). CONCLUSION: Both models of psychotherapy were effective in increasing mature defenses and decreasing immature ones, as well as decreasing depressive symptoms at all evaluation times. With this, it is understood that a greater understanding of these interactions will allow a more adequate diagnostic and prognostic evaluation and the design of useful strategies that adapt to the patient's reality.


Asunto(s)
Trastorno Depresivo Mayor , Psicoterapia Breve , Humanos , Adulto , Trastorno Depresivo Mayor/terapia , Psicoterapia , Mecanismos de Defensa , Ego
14.
Gene ; 862: 147281, 2023 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-36775216

RESUMEN

In the context of cancer predisposition syndromes, it is widely known that the correct interpretation of germline variants identified in multigene panel testing is essential for adequate genetic counseling and clinical decision making, in which variants of uncertain significance (VUS) are not considered actionable findings. Thus, their periodic re-evaluation using appropriate guidelines is notably important. In the present study, we compared the performance of the main variant classification guidelines (ACMG, Sherloc and ENIGMA) in variant reassessment, using as input a BRCA1/2 VUS case series (retrospective analysis) from Brazil, an ethnically diverse and admixed country with substantial challenges in VUS reclassification. As main findings, two of the 15 VUS analyzed were reclassified as likely pathogenic by the 3 guidelines, BRCA1 c.4987-3C > G (rs397509213) and BRCA2 c.7868A > G (rs80359012). Moreover, challenges in variant classification and reassessment are described and additional in silico data about structural impact of the variant BRCA2 c.7868A > G are provided. We hypothesize that the establishment of a framework to reassess VUS could improve this process in health centers that have not yet implemented this practice. Results of this study underscore that periodic monitoring of the functional, clinical, and bioinformatics data of a VUS by a multidisciplinary team are of utmost importance in clinical practice. When there is a specific guideline for a given gene, such as ENIGMA for BRCA1/2, it should be considered the first option for variant assessment. Finally, recruitment of VUS carriers and their relatives to participate in variant segregation studies and publication of VUS reclassification results in the international scientific literature should be encouraged.


Asunto(s)
Neoplasias de la Mama , Predisposición Genética a la Enfermedad , Humanos , Femenino , Estudios Retrospectivos , Pruebas Genéticas/métodos , Proteína BRCA2/genética , Asesoramiento Genético , Síndrome , Proteína BRCA1/genética , Neoplasias de la Mama/genética
15.
Epigenetics ; 18(1): 2145061, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36411728

RESUMEN

Zika virus (ZIKV) cause Congenital Zika Syndrome (CZS) in individuals exposed during pregnancy. Studies have shown that ZIKV infection positively regulates the miR-124 expression in neural cells, which leads to a decrease of TFRC, a gene targeted of this miRNA. Both miR-124 and TFRC exhibit a pivotal role in nervous system development. Therefore, in this study we aimed to investigate whether genetic variants that affect the expression of these genes could act together with ZIKV to increase the risk of individuals developing CZS. TFRC rs406271 and MIR-124-1 rs531564 polymorphisms were genotyped, using TaqMan® Genotyping Assays, in a sample of children who were exposed to ZIKV during pregnancy, of whom 40 were born with CZS and 48 without congenital anomalies. We identified that individuals with CZS presented a higher frequency of CG genotype of rs531564 polymorphism in MIR-124-1 (p=0.048), which is associated with increased expression of miR-124. Since ZIKV also upregulates the expression of this miRNA, the presence of CG genotype in individuals exposed to the virus could lead to a scenario of overexpression of miR-124 in the brain. Since teratogenesis is a multifactorial event, this genetic finding could partly explain why such individuals are more susceptible to CZS, considering both the downregulation of important neurodevelopment genes, as well as deregulation of the neurogenesis process. Thus, we provide preliminary evidence about a possible genetic risk factor to CZS and highlight the importance of analyzing functional polymorphisms related to epigenetic modulators of neurodevelopment genes in the context of ZIKV teratogenesis.


Asunto(s)
MicroARNs , Teratogénesis , Infección por el Virus Zika , Virus Zika , Embarazo , Niño , Femenino , Humanos , Infección por el Virus Zika/epidemiología , Infección por el Virus Zika/genética , Virus Zika/genética , Teratogénesis/genética , Metilación de ADN
16.
Arq Neuropsiquiatr ; 80(9): 970-972, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-36252738

RESUMEN

Augusta Dejerine-Klumpke was ahead of her time, with extensive contributions to the field of neuroanatomy and neurology, achieving international recognition. Despite her great contribution to world neurology, she was expelled from the Salpêtrière hospital in 1917, due to the rivalry and mutual hatred between Pierre Marie and his rival Jules Déjerine, her husband and collaborator.


Augusta Dejerine-Klumpke era uma pessoa à frente de seu tempo, com extensas contribuições para o campo da neuroanatomia e neurologia, alcançando reconhecimento internacional. Apesar de sua grande contribuição para a neurologia mundial, ela foi expulsa do hospital Salpêtrière em 1917, devido à grande rivalidade e ódio mútuo entre Pierre Marie e seu rival Jules Dejerine.


Asunto(s)
Neurología , Humanos , Femenino , Neuroanatomía , Hospitales
17.
Infect Genet Evol ; 98: 105228, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-35104680

RESUMEN

The investigation of conventional complete blood-count (CBC) data for classifying the SARS-CoV-2 infection status became a topic of interest, particularly as a complementary laboratory tool in developing and third-world countries that financially struggled to test their population. Although hematological parameters in COVID-19-affected individuals from Asian and USA populations are available, there are no descriptions of comparative analyses of CBC findings between COVID-19 positive and negative cases from Latin American countries. In this sense, machine learning techniques have been employed to examine CBC data and aid in screening patients suspected of SARS-CoV-2 infection. In this work, we used machine learning to compare CBC data between two highly genetically distinguished Latin American countries: Brazil and Ecuador. We notice a clear distribution pattern of positive and negative cases between the two countries. Interestingly, almost all red blood cell count parameters were divergent. For males, neutrophils and lymphocytes are distinct between Brazil and Ecuador, while eosinophils are distinguished for females. Finally, neutrophils, lymphocytes, and monocytes displayed a particular distribution for both genders. Therefore, our findings demonstrate that the same set of CBC features relevant to one population is unlikely to apply to another. This is the first study to compare CBC data from two genetically distinct Latin American countries.


Asunto(s)
COVID-19/sangre , COVID-19/fisiopatología , Pruebas Hematológicas/métodos , Pruebas Hematológicas/estadística & datos numéricos , Tamizaje Masivo/métodos , Tamizaje Masivo/estadística & datos numéricos , SARS-CoV-2/patogenicidad , Adulto , Anciano , Anciano de 80 o más Años , Brasil/epidemiología , Ecuador/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad
18.
Braz J Psychiatry ; 44(5): 469-477, 2022 11 05.
Artículo en Inglés | MEDLINE | ID: mdl-35896153

RESUMEN

OBJECTIVE: To evaluate the impact of defense mechanisms at baseline on depressive symptoms after brief psychotherapies and after 6-months of follow-up among depressed patients with and without cluster B personality disorders (PDs). METHODS: This quasi-experimental study nested within a randomized clinical trial included a clinical sample of adults (18-60 years) diagnosed with major depressive disorder using the Mini-International Neuropsychiatric Interview. The Millon Clinical Multiaxial Inventory-III was applied to assess PD, the Defense Style Questionnaire 40 was used to analyze defense mechanisms, and the Beck Depression Inventory was used to measure the severity of depressive symptoms. Adjusted analysis was performed by linear regression. RESULTS: The final sample consisted of 177 patients diagnosed with major depressive disorder, of whom 39.5% had cluster B PDs. Immature defenses at baseline significantly predicted the persistence of depressive symptoms at post-intervention and at 6-months of follow-up only in patients with PDs. CONCLUSION: In depressed patients with cluster B PDs, immature defenses predicted a poor response to brief therapies. The assessment of immature defenses at baseline can help identify patients at greater risk of poor therapeutic results and enable more appropriate treatment choices.


Asunto(s)
Trastorno Depresivo Mayor , Humanos , Adulto , Trastorno Depresivo Mayor/terapia , Trastorno Depresivo Mayor/diagnóstico , Trastornos de la Personalidad/psicología , Psicoterapia , Escalas de Valoración Psiquiátrica , Mecanismos de Defensa
19.
Anal Chem ; 83(18): 7035-43, 2011 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-21809823

RESUMEN

Biomedical sciences, and in particular biomarker research, demand efficient glycoprotein enrichment platforms. Herein magnetic nanoprobes (MNP), after being coated with three broad-spectrum lectins-concanavalin A (ConA), wheat germ agglutinin (WGA), and Maackia amurensis lectin (MA)-were utilized to selectively capture glycoproteins from human body fluids. Additionally, a new methodology, based on protection of the lectins with their target sugars prior to coupling with MNPs, was proposed to overcome the nonspecific nature of conjugation. This approach contributed to preserve lectin conformation, increasing by 40% and 90% the affinity of ConA and MA for glycoproteins in relation to synthesis with nonprotected lectins. Optimal operating conditions (temperature, time) and maximum binding capacities were further determined for each lectin by use of fetuin as a reference. The enhanced performance of lectin-based nanoplatforms was demonstrated by comparing MNP@ConA with conventional Sepharose@ConA. These experiments have shown that ConA immobilized on MNP exhibited 5 times higher affinity for fetuin and ovalbumin when compared with Sepharose@ConA with the same amount of immobilized lectin. MNP@Lectins were then applied to human serum, saliva, and urine and the recovered proteins were digested with trypsin and analyzed by nano-HPLC MALDI-TOF/TOF. This allowed the identification of 180 proteins, 90% of which were found to be glycosylated by use of bioinformatics tools, therefore revealing low levels of unspecific binding. Thus, MNP@lectins have proved to be a valuable tool for glycoproteomic studies, particularly when dealing with minute amounts of material.


Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Glicoproteínas/análisis , Lectinas/metabolismo , Nanopartículas de Magnetita/química , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Concanavalina A/química , Concanavalina A/metabolismo , Fetuínas/metabolismo , Glicoproteínas/sangre , Glicoproteínas/orina , Glicosilación , Humanos , Proteínas Inmovilizadas/química , Proteínas Inmovilizadas/metabolismo , Lectinas/química , Ovalbúmina/metabolismo , Unión Proteica , Saliva/metabolismo , Sefarosa/análogos & derivados , Sefarosa/química , Sefarosa/metabolismo , Tripsina/metabolismo , Aglutininas del Germen de Trigo/química , Aglutininas del Germen de Trigo/metabolismo
20.
Public Health Nutr ; 14(4): 661-9, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-20939941

RESUMEN

OBJECTIVE: To assess the dependence on fish consumption of families and its impact on nutritional status and neurodevelopment of pre-school children. DESIGN: Cross-sectional study that measured children's hair mercury (HHg) as an indicator of family fish consumption, growth (anthropometric Z-scores, WHO standards) and neurological (Gesell developmental scores (GDS)) development. SETTING: Traditional living conditions among families residing in the area adjacent to the Samuel Dam (Western Amazon) hydroelectric reservoir. SUBJECTS: Two hundred and forty-nine pre-school children (1-59 months of age) from families transitioning from the traditional Amazonian lifestyle. RESULTS: Family fish consumption was significantly correlated with children's HHg concentration (Spearman's r=0.246, P<0.0001); however, HHg had no significant association with growth (Z-scores). Overall, the prevalence of severe malnutrition, i.e. stunting (height-for-age Z-score (HAZ)≤-3), underweight (weight-for-age Z-score (WAZ)≤-3) and wasting (weight-for-height Z-score (WHZ)≤-3) was 5.2% (n 13), 0% and 0.8% (n 2), respectively. The prevalence of moderate stunting (HAZ≥-3 to ≤-2), underweight (WAZ≥-3 to ≤-2) and wasting (WHZ≥-3 to ≤-2) was 8.8% (n 22), 2.4% (n 6) and 4.8% (n 12), respectively. Although 76% of the children showed adequate GDS (>85), multiple regression analysis showed that fish consumption (as HHg) had no impact on GDS, but that some variables did interact significantly with specific domains (motor and language development). CONCLUSIONS: The study showed that the families' shift in fish consumption had no negative impact on the growth of young children and that ensuing methylmercury exposure has not been a noticeable neurodevelopmental hindrance.


Asunto(s)
Desarrollo Infantil/efectos de los fármacos , Trastornos de la Nutrición del Niño/epidemiología , Estilo de Vida , Compuestos de Metilmercurio , Alimentos Marinos/análisis , Animales , Brasil , Desarrollo Infantil/fisiología , Preescolar , Estudios Transversales , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/análisis , Femenino , Peces/metabolismo , Contaminación de Alimentos , Cabello/química , Humanos , Lactante , Masculino , Compuestos de Metilmercurio/administración & dosificación , Compuestos de Metilmercurio/efectos adversos , Compuestos de Metilmercurio/análisis , Estado Nutricional , Centrales Eléctricas , Alimentos Marinos/estadística & datos numéricos
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