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1.
Cell ; 143(3): 367-78, 2010 Oct 29.
Artículo en Inglés | MEDLINE | ID: mdl-21029860

RESUMEN

ATRX is an X-linked gene of the SWI/SNF family, mutations in which cause syndromal mental retardation and downregulation of α-globin expression. Here we show that ATRX binds to tandem repeat (TR) sequences in both telomeres and euchromatin. Genes associated with these TRs can be dysregulated when ATRX is mutated, and the change in expression is determined by the size of the TR, producing skewed allelic expression. This reveals the characteristics of the affected genes, explains the variable phenotypes seen with identical ATRX mutations, and illustrates a new mechanism underlying variable penetrance. Many of the TRs are G rich and predicted to form non-B DNA structures (including G-quadruplex) in vivo. We show that ATRX binds G-quadruplex structures in vitro, suggesting a mechanism by which ATRX may play a role in various nuclear processes and how this is perturbed when ATRX is mutated.


Asunto(s)
ADN Helicasas/metabolismo , Proteínas Nucleares/metabolismo , Animales , Células Cultivadas , Inmunoprecipitación de Cromatina , Cromosomas de los Mamíferos/metabolismo , Islas de CpG , ADN Helicasas/genética , ADN Ribosómico/metabolismo , G-Cuádruplex , Expresión Génica , Estudio de Asociación del Genoma Completo , Histonas/metabolismo , Humanos , Ratones , Repeticiones de Minisatélite , Mutación , Proteínas Nucleares/genética , Telómero/metabolismo , Proteína Nuclear Ligada al Cromosoma X
2.
Purinergic Signal ; 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38976175

RESUMEN

Medulloblastoma is the most common malignant tumor in the pediatric population. Its classification has incorporated key molecular variations alongside histological characterization. CD39 (also known as ENTPD1) and CD73 (also known as NT5E), enzymes of the purinergic signaling pathway, act in synergy to generate extracellular adenosine, creating an immunosuppressive tumor microenvironment. Our study examined the expression of mRNA of these genes in previously described transcriptome data sets of medulloblastoma patient samples from the Cavalli Cohort (n = 763). Survival distribution was estimated according to the Kaplan-Meier method using a median cut-off and log-rank statistics (p ≤ 0.05). In non-WNT and non-SHH medulloblastoma Group 4 (n = 264), the high expression of ENTPD1 and NT5E was significantly related to a lower overall survival (p = 2.7e-04; p = 2.6e-03). In the SHH-activated group (n = 172), the high expression of ENTPD1 was significantly related to lower overall survival (p = 7.8e-03), while the high expression of NT5E was significantly related to greater overall survival (p = 0.017). In the WNT group (n = 63), the expressions of ENTPD1 and NT5E were not significantly correlated with overall survival (p = 0.212; p = 0.101). In non-WNT and non-SHH medulloblastoma Group 3 (n = 113), the high expression of ENTPD1 was significantly related to greater survival (p = 0.034), while expression of NT5E was not significantly related to survival of patients (p = 0.124). This in silico analysis indicates that ENTPD1 (CD39) and NT5E (CD73) can be seen as potential prognostic markers and therapeutic targets for primary medulloblastomas in non-WNT and non-SHH Group 4.

3.
Pain Med ; 25(1): 8-12, 2024 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-37656943

RESUMEN

OBJECTIVES: To describe and assess the feasibility of an ultrasound-guided technique for intra-articular injection of the costovertebral joints, in an unembalmed cadaveric specimen, utilizing fluoroscopy and cone beam computerized tomography for confirmation of contrast spread and needle tip position, respectively. METHODOLOGY: A single unembalmed cadaveric specimen was obtained. A single interventionist performed the placement of the needles under ultrasound guidance. Contrast dye was then injected through each of the needles under real-time fluoroscopy. Finally, the specimen was submitted to a cone beam computerized tomography with 3-dimensional acquisition and multiplanar reformatting to assess final needle tip position relative to the costovertebral joints. RESULTS: In total, 18 spinal needles were placed under ultrasound guidance. Fluoroscopy showed 4 distinct patterns of contrast spread: intra-articular in the costovertebral joint (13 levels in total), epidural (1 level), intra-articular in the facet joint of the target level (3 levels), and undetermined (1 level). Cone-beam computerized tomography confirmed 13 out of 18 needles to be adequately placed in the costovertebral joints (72% of the total) and 5 out of the 18 needles to be misplaced: 3 needles were placed in the facet joint of the target level, and 2 needles were placed in the epidural space. CONCLUSIONS: This study suggests that, when performed by experienced interventionists, this technique has an accuracy rate of 72%. Further studies are warranted before these results can be extrapolated to daily clinical practice.


Asunto(s)
Agujas , Ultrasonografía Intervencional , Humanos , Estudios de Factibilidad , Ultrasonografía Intervencional/métodos , Tomografía Computarizada por Rayos X , Fluoroscopía/métodos , Cadáver
4.
Cochrane Database Syst Rev ; 7: CD014920, 2024 07 03.
Artículo en Inglés | MEDLINE | ID: mdl-38958136

RESUMEN

BACKGROUND: Postoperative myocardial infarction (POMI) is associated with major surgeries and remains the leading cause of mortality and morbidity in people undergoing vascular surgery, with an incidence rate ranging from 5% to 20%. Preoperative coronary interventions, such as coronary artery bypass grafting (CABG) or percutaneous coronary interventions (PCI), may help prevent acute myocardial infarction in the perioperative period of major vascular surgery when used in addition to routine perioperative drugs (e.g. statins, angiotensin-converting enzyme inhibitors, and antiplatelet agents), CABG by creating new blood circulation routes that bypass the blockages in the coronary vessels, and PCI by opening up blocked blood vessels. There is currently uncertainty around the benefits and harms of preoperative coronary interventions. OBJECTIVES: To assess the effects of preoperative coronary interventions for preventing acute myocardial infarction in the perioperative period of major open vascular or endovascular surgery. SEARCH METHODS: We searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE Ovid, Embase Ovid, LILACS, and CINAHL EBSCO on 13 March 2023. We also searched the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) or quasi-RCTs that compared the use of preoperative coronary interventions plus usual care versus usual care for preventing acute myocardial infarction during major open vascular or endovascular surgery. We included participants of any sex or any age undergoing major open vascular surgery, major endovascular surgery, or hybrid vascular surgery. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes of interest were acute myocardial infarction, all-cause mortality, and adverse events resulting from preoperative coronary interventions. Our secondary outcomes were cardiovascular mortality, quality of life, vessel or graft secondary patency, and length of hospital stay. We reported perioperative and long-term outcomes (more than 30 days after intervention). We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included three RCTs (1144 participants). Participants were randomised to receive either preoperative coronary revascularisation with PCI or CABG plus usual care or only usual care before major vascular surgery. One trial enrolled participants if they had no apparent evidence of coronary artery disease. Another trial selected participants classified as high risk for coronary disease through preoperative clinical and laboratorial testing. We excluded one trial from the meta-analysis because participants from both the control and the intervention groups were eligible to undergo preoperative coronary revascularisation. We identified a high risk of performance bias in all included trials, with one trial displaying a high risk of other bias. However, the risk of bias was either low or unclear in other domains. We observed no difference between groups for perioperative acute myocardial infarction, but the evidence is very uncertain (risk ratio (RR) 0.28, 95% confidence interval (CI) 0.02 to 4.57; 2 trials, 888 participants; very low-certainty evidence). One trial showed a reduction in incidence of long-term (> 30 days) acute myocardial infarction in participants allocated to the preoperative coronary interventions plus usual care group, but the evidence was very uncertain (RR 0.09, 95% CI 0.03 to 0.28; 1 trial, 426 participants; very low-certainty evidence). There was little to no effect on all-cause mortality in the perioperative period when comparing the preoperative coronary intervention plus usual care group to usual care alone, but the evidence is very uncertain (RR 0.79, 95% CI 0.31 to 2.04; 2 trials, 888 participants; very low-certainty evidence). The evidence is very uncertain about the effect of preoperative coronary interventions on long-term (follow up: 2.7 to 6.2 years) all-cause mortality (RR 0.74, 95% CI 0.30 to 1.80; 2 trials, 888 participants; very low-certainty evidence). One study reported no adverse effects related to coronary angiography, whereas the other two studies reported five deaths due to revascularisations. There may be no effect on cardiovascular mortality when comparing preoperative coronary revascularisation plus usual care to usual care in the short term (RR 0.07, 95% CI 0.00 to 1.32; 1 trial, 426 participants; low-certainty evidence). Preoperative coronary interventions plus usual care in the short term may reduce length of hospital stay slightly when compared to usual care alone (mean difference -1.17 days, 95% CI -2.05 to -0.28; 1 trial, 462 participants; low-certainty evidence). We downgraded the certainty of the evidence due to concerns about risk of bias, imprecision, and inconsistency. None of the included trials reported on quality of life or vessel graft patency at either time point, and no study reported on adverse effects, cardiovascular mortality, or length of hospital stay at long-term follow-up. AUTHORS' CONCLUSIONS: Preoperative coronary interventions plus usual care may have little or no effect on preventing perioperative acute myocardial infarction and reducing perioperative all-cause mortality compared to usual care, but the evidence is very uncertain. Similarly, limited, very low-certainty evidence shows that preoperative coronary interventions may have little or no effect on reducing long-term all-cause mortality. There is very low-certainty evidence that preoperative coronary interventions plus usual care may prevent long-term myocardial infarction, and low-certainty evidence that they may reduce length of hospital stay slightly, but not cardiovascular mortality in the short term, when compared to usual care alone. Adverse effects of preoperative coronary interventions were poorly reported in trials. Quality of life and vessel or graft patency were not reported. We downgraded the certainty of the evidence most frequently for high risk of bias, inconsistency, or imprecision. None of the analysed trials provided significant data on subgroups of patients who could potentially experience more substantial benefits from preoperative coronary intervention (e.g. altered ventricular ejection fraction). There is a need for evidence from larger and homogeneous RCTs to provide adequate statistical power to assess the role of preoperative coronary interventions for preventing acute myocardial infarction in the perioperative period of major open vascular or endovascular surgery.


Asunto(s)
Puente de Arteria Coronaria , Procedimientos Endovasculares , Infarto del Miocardio , Intervención Coronaria Percutánea , Complicaciones Posoperatorias , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Infarto del Miocardio/prevención & control , Infarto del Miocardio/mortalidad , Intervención Coronaria Percutánea/efectos adversos , Puente de Arteria Coronaria/efectos adversos , Puente de Arteria Coronaria/mortalidad , Puente de Arteria Coronaria/métodos , Complicaciones Posoperatorias/prevención & control , Procedimientos Endovasculares/métodos , Procedimientos Endovasculares/efectos adversos , Procedimientos Quirúrgicos Vasculares/efectos adversos , Procedimientos Quirúrgicos Vasculares/mortalidad , Cuidados Preoperatorios/métodos , Sesgo , Periodo Perioperatorio , Tiempo de Internación
5.
Odontology ; 112(4): 1167-1177, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38514512

RESUMEN

To evaluate the impact on the quality of filling with of low-fusion and conventional gutta-percha cones. Thirty-six maxillary canines were prepared and divided into three groups: I-conventional cone with Downpack at 200 °C at 4 mm from the WL; II-low-fusion cone with Downpack at 100 °C up to 4 mm from the WL; III-low-fusion cone with Downpack at 100 °C up to 7 mm from the WL. Temperature variations were measured in thirds on the external surface of the root. The bond strength was evaluated using the push-out test. The adhesive interface was analyzed by scanning electron microscopy. The bond strength and the temperature variation data were analyzed using analysis of variance and the failure type using the chi-square test. The low-fusion cone group with 7 mm Downpack showed higher bond strength (4.2 ± 2.7) compared with conventional cones (2.8 ± 1.6) and low-fusion cones with 4 mm Downpack (2.9 ± 1.6) (p < 0.05), with occurrence of a higher number of adhesive failures to the filling material and mixed failures. Relative to temperature variation, there was less temperature change in the apical third, in the low-fusion cone with Downpack 7 mm (1.0 ± 1.0) (p < 0.05). The use of low-fusion cones allowed the continuous wave condensation technique to be performed at a lower depth of Downpack at 100 °C at 7 mm, with less heating in the apical third, without compromising the quality of filling. Using gutta-percha cones with low fusion, which permits a lower condensation temperature and reduced Downpack depth, maintains the quality of filling, in order to minimize possible damage to the periapical tissues.


Asunto(s)
Recubrimiento Dental Adhesivo , Gutapercha , Ensayo de Materiales , Microscopía Electrónica de Rastreo , Materiales de Obturación del Conducto Radicular , Obturación del Conducto Radicular , Gutapercha/química , Materiales de Obturación del Conducto Radicular/química , Obturación del Conducto Radicular/métodos , Humanos , Recubrimiento Dental Adhesivo/métodos , Técnicas In Vitro , Cerámica/química , Propiedades de Superficie , Diente Canino , Análisis del Estrés Dental , Temperatura
6.
J Esthet Restor Dent ; 2024 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-39377103

RESUMEN

OBJECTIVES: To evaluate the effects of dentifrices containing sodium fluoride (NaF) combined with NovaMin (Sensodyne Repair & Protect-SRP), NaF combined with stannous fluoride (SnF2, Oral-B Pro-Gengiva-OBP), and amine fluoride (AmF, Colgate Elmex-ELM) on enamel subjected to simulated erosive cycling. MATERIALS AND METHODS: Bovine enamel-dentin discs (n = 10/group) were subjected to erosive cycling with orange juice (pH = 3.29, 5 min, 3x/day), artificial saliva (SA-2 h, 3x/day and overnight) and treated with dentifrice (2 min, 2x/day) or without treatment (CONT). Surface microhardness (SMH) was evaluated at baseline (T0), on the first (T1) and fifth (T5) days. SMH loss (%SHL) was calculated. Surface roughness (Ra, µm) was determined at T0 and T5. Morphology and mineral content were evaluated under scanning electron microscopy and energy-dispersive x-ray spectroscopy. Data were analyzed using ANOVA/Tukey or Bonferroni (α = 5%). RESULTS: No differences in %SHL were detected among groups at T1. At T5, OBP promoted %SHL, Ra, and ΔRa significantly lower than all the other groups (p < 0.05). All groups exhibited morphological changes in topography and similar Ca/P means before and after treatments. CONCLUSIONS: Dentifrice containing SnF2 minimized the negative effects on the SMH and Ra caused by exposure to orange juice after 5 days of simulated cycling. CLINICAL RELEVANCE: Patients who are more exposed to risk factors for dental erosion could benefit from the use of dentifrice containing SnF2.

7.
Public Health Nurs ; 41(3): 589-601, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38528749

RESUMEN

OBJECTIVE: To understand the factors associated with the practice of chemsex among MSM in Brazil, especially during the Mpox health crisis, and to design effective prevention and intervention strategies specifically for this population. DESIGN: A cross-sectional and analytical study using an electronic survey, conducted from September to December 2022, during the peak of the Mpox outbreak in Brazil. SAMPLE: A total of 1452 MSM aged 18 and older. MEASUREMENTS: Data were collected via the REDCap platform through a survey with 46 questions. These addressed demographic data, sexual affiliations, practices, experiences with Mpox, healthcare service usage, and stigma or fear related to Mpox. RESULTS: The prevalence of chemsex was 19.42% (n = 282). Multivariate Poisson modeling indicated a high incidence of chemsex among those diagnosed with Mpox and those involved in high-risk behaviors. The practice of chemsex was six times higher among those diagnosed with Mpox (95% CI: 4.73-9.10). MSM who engage in bugchasing had a prevalence twice that of the main outcome (95% CI: 1.31-3.16). CONCLUSION: There is a significant need for targeted interventions for MSM in Brazil, especially given the Mpox outbreak. This study highlights the strong relationships between chemsex, experiences with Mpox, and various sexual behaviors, underscoring the importance of effective public health initiatives.


Asunto(s)
Infecciones por VIH , Mpox , Minorías Sexuales y de Género , Trastornos Relacionados con Sustancias , Masculino , Humanos , Homosexualidad Masculina , Brasil/epidemiología , Estudios Transversales , Trastornos Relacionados con Sustancias/epidemiología , Conducta Sexual , Infecciones por VIH/epidemiología
8.
Nurs Inq ; 31(3): e12635, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38558441

RESUMEN

Our goal was to explore self-care practices among men who have sex with men in the context of Mpox in Brazil. This study used qualitative research methods, including interviews and thematic analysis, to collect and analyze data from male participants across the Brazilian territory. The narratives unveil men's perspectives on self-care, risk reduction, and health beliefs during the Mpox pandemic. Our findings highlight a multifaceted approach to self-care among men, encompassing hygiene, physical contact management, mask usage, skin lesion vigilance, and adherence to official guidelines. Men's attitudes toward sexual behaviors emphasize the importance of reducing sexual partners, practicing safe sex, and combating misinformation through accurate information dissemination. The development of these behaviors and self-care practices can be facilitated by nurses guided by Dorothea Orem's Self-Care Theory, supported by patient-centered care, with strategies to address and confront the stigma associated with the disease and provide emotional support. Thus, the study underscores the pivotal role of self-care in mitigating infection risks, especially in the context of emerging infectious diseases. It acknowledges the impact of socio-cultural factors and healthcare policies on men's preventive measures. However, it also recognizes limitations, such as potential bias due to stigma concerns and a nonrepresentative sample. Ultimately, the research advocates for tailored education, promotion of gender equity, and healthcare empowerment to effectively manage health risks in such contexts.


Asunto(s)
Enfermedades Transmisibles Emergentes , Investigación Cualitativa , Autocuidado , Humanos , Masculino , Brasil , Autocuidado/psicología , Adulto , Enfermedades Transmisibles Emergentes/prevención & control , Homosexualidad Masculina/psicología , Persona de Mediana Edad , Conocimientos, Actitudes y Práctica en Salud , Pandemias
9.
Purinergic Signal ; 2023 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-37402102

RESUMEN

Glioblastoma (GB) is the most common primary brain tumor in adults and carries a dismal prognosis, despite the best available treatment. The 2021 WHO Classification of CNS tumors incorporated molecular profiling to better define the characteristics and prognosis of tumor types and subtypes. These recent advances in diagnosis have not yet resulted in breakthrough therapies capable of shifting the treatment paradigm. NT5E/CD73 is a cell surface enzyme that participates in a complex purinergic pathway in synergy with ENTPD1/CD39 producing extracellular adenosine (ADO) from ATP. ADO promotes tumor progression by inducing immunosuppression, stimulating adhesion, invasion, and angiogenesis. In this study, we performed an in silico analysis of 156 human glioblastoma samples in an unexplored public database to investigate the transcriptional levels of NT5E and ENTPD1. The analysis revealed a significant increase in transcription levels of the genes under study in GB samples versus non-tumor brain tissue samples, in concordance with previous studies. High transcriptional levels of NT5E or ENTPD1 were independently related to a decrease in overall survival (p = 5.4e-04; 1.1e-05), irrespective of the IDH mutation status. NT5E transcriptional levels were significantly higher in GB IDH wild-type patients compared to GB IDH-mutant; however, ENTPD1 levels showed no significant difference, p ≤ 0.001. This in silico study indicates the need for a deeper understanding of the purinergic pathway relation to GB development, also inspiring future population studies that could explore ENTPD1 and NT5E not only as prognostic markers but also as potential therapeutic targets.

10.
Vasc Med ; 28(1): 36-44, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36759936

RESUMEN

INTRODUCTION: Evaluation of limb hemodynamics using the ankle-brachial index (ABI) may be difficult due to skin lesions, extensive necrosis, and obesity, such as commonly present in patients with diabetes with chronic limb-threatening ischemia (CLTI). We hypothesized that the pedal acceleration time (PAT) correlates with ABI and Wound, Ischemia, and foot Infection (WIfI) scores in patients with diabetes to serve as a new modality to accurately stage CLTI. METHODS: A single-center, cross-sectional study included patients with and without diabetes > 18 years with CLTI. Limbs were categorized in three grades of ischemia based on the ABI (ABI < 0.8, < 0.6, and < 0.4) and in two classes based on WIfI stages of amputation risk. Receiver operator characteristic (ROC) curves were used to determine PAT sensitivity, specificity, and accuracy to predict lower-limb ischemia. RESULTS: A total of 141 patients (67 nondiabetic and 74 diabetic) and 198 lower limbs (94 nondiabetic and 104 diabetic) met the inclusion criteria. In patients without diabetes, the accuracy of PAT for detecting an ABI < 0.8 was 85%; for detecting an ABI < 0.6 was 85%; and for detecting an ABI < 0.4 was 87%. In patients with diabetes, the accuracy of PAT in detecting an ABI < 0.8 was 91%; for detecting an ABI < 0.6 was 79%; and for detecting an ABI < 0.4 was 88%. In patients without diabetes, the accuracy for detecting WIfI stages of moderate and high amputation risk was 77% and for patients with diabetes was also 77%. CONCLUSIONS: PAT shows high correlation with the ABI as well as with the WIfI stages of amputation risk and the grades of ischemia, with high accuracy.


Asunto(s)
Diabetes Mellitus , Enfermedad Arterial Periférica , Humanos , Estudios Transversales , Factores de Riesgo , Resultado del Tratamiento , Recuperación del Miembro , Estudios Retrospectivos , Isquemia , Medición de Riesgo
11.
J Clin Densitom ; 26(1): 97-103, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36543669

RESUMEN

BACKGROUND: Despite the well-established role of muscle in maintaining bone mass and physical performance, there are still few studies that assess the relationship between muscle groups and specific bone sites and its contribution to physical function in older people. The aim of the study is to verify the association between hip and knee's muscle strength and bone mineral density of the femoral neck (BMD-FN) and investigated which muscle strength that are related with BMD-FN is associated with physical function in older women. METHODOLOGY: This is a cross-sectional study of 94 women over the age of 60 years, physically independent. Muscle strength of the hip and knee was evaluated using an isokinetic dynamometer (Biodex, USA) to obtain peak torque (PT). The BMD-FN was obtained using dual-energy x-ray absorption densitometry (DXA). Physical function was evaluated by the Timed Up and Go (TUG), gait speed (GS), five times stand to sit (5TSS) and single-leg stance (SS). To verify the association between muscle strength (independent variable) and the BMD-FN (dependent variable) and the relationship between muscle strength (independent variable) and clinical tests (dependent variable), the multiple linear regression was carried out, adjusted for age, time of menopause, height and level of physical activity. All of the analyses were carried out by the SPSS 17.0 software, with a level of p < 0.05 significance. RESULTS: We found an association between the hip abductors PT and the BMD-FN and between hip abductors PT and all clinical tests. CONCLUSION: We observe that hip abductor muscle strength contributes to BMD-FN and to performance in several clinical tests in older women. These findings reinforce the importance of this musculature not only for improving balance and gait, but also it can be a strategy to maintain/improve bone mass in the femoral neck in this population.


Asunto(s)
Densidad Ósea , Músculo Esquelético , Humanos , Femenino , Anciano , Persona de Mediana Edad , Densidad Ósea/fisiología , Estudios Transversales , Músculo Esquelético/diagnóstico por imagen , Músculo Esquelético/fisiología , Absorciometría de Fotón , Cuello Femoral/diagnóstico por imagen , Cuello Femoral/fisiología
12.
Mol Cell Proteomics ; 20: 100091, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33971369

RESUMEN

Non-T cell activation linker (NTAL) membrane protein depletion from lipid rafts by alkylphospholipids or downregulation by shRNA knockdown decreases cell viability through regulation of the Akt/PI3K pathway in mantle cell lymphoma and acute promyelocytic leukemia cells. Here, we confirmed that the knockdown of NTAL in acute myeloid leukemia (AML) cell lines was associated with decreased cell proliferation and survival. Similarly, a xenograft model using AML cells transduced with NTAL-shRNA and transplanted into immunodeficient mice led to a 1.8-fold decrease in tumor burden. Using immunoprecipitation, LC-MS/MS analysis, and label-free protein quantification, we identified interactors of NTAL in two AML cell lines. By evaluating the gene expression signatures of the NTAL protein interactors using the PREdiction of Clinical Outcomes from Genomic Profiles database, we found that 12 NTAL interactors could predict overall survival in AML, in at least two independent cohorts. In addition, patients with AML exhibiting a high expression of NTAL and its interactors were associated with a leukemic granulocyte-macrophage progenitor-like state. Taken together, our data provide evidence that NTAL and its protein interactors are relevant to AML cell proliferation and survival and represent potential therapeutic targets for granulocyte-macrophage progenitor-like leukemias.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Leucemia Mieloide Aguda/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Animales , Línea Celular Tumoral , Proliferación Celular , Supervivencia Celular , Humanos , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/patología , Masculino , Ratones Endogámicos NOD , Ratones SCID , Fosforilación , Mapas de Interacción de Proteínas , Proteínas Proto-Oncogénicas c-akt/metabolismo , Análisis de Supervivencia , Transcriptoma
13.
Oral Dis ; 29(2): 649-660, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34510641

RESUMEN

OBJECTIVES: To investigate the potential effect of fatty acid synthase (FASN) inhibitor orlistat to enhance the effectiveness of chemotherapy drugs widely used to treat oral squamous cell carcinomas (OSCC), such as 5-fluorouracil, cisplatin, and paclitaxel. METHODS: The OSCC SCC-9 LN-1 metastatic cell line, which expresses high levels of FASN, was used for drug combination experiments. Cell viability was analyzed by crystal violet staining and automatic cell counting. Apoptosis and cell cycle were analyzed by flow cytometry with Annexin-V/7-AAD and propidium iodide staining, respectively. Cyclin B1, Cdc25C, Cdk1, FASN, and ERBB2 levels were assessed by Western blotting. Finally, cell scratch and transwell assays were performed to assess cell migration and invasion. RESULTS: Inhibition of FASN with orlistat sensitized SCC-9 LN-1 cells to the cytotoxic effects of paclitaxel and cisplatin, but not 5-fluorouracil, which was accompanied by a significant reduction in cyclin B1. The suppression of proliferation, migration, and invasion of SCC-9 LN-1 cells induced by orlistat plus cisplatin or paclitaxel was not superior to the effects of chemotherapy drugs alone. CONCLUSION: Our results suggest that orlistat enhances the chemosensitivity of SCC-9 LN-1 cells to cisplatin and paclitaxel by downregulating cyclin B1.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Humanos , Cisplatino/farmacología , Paclitaxel/farmacología , Paclitaxel/uso terapéutico , Orlistat/farmacología , Orlistat/uso terapéutico , Carcinoma de Células Escamosas de Cabeza y Cuello , Ciclina B1/farmacología , Ácido Graso Sintasas/metabolismo , Ácido Graso Sintasas/farmacología , Neoplasias de la Boca/tratamiento farmacológico , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/patología , Fluorouracilo/farmacología , Línea Celular Tumoral , Apoptosis , Proliferación Celular , Acido Graso Sintasa Tipo I
14.
Int J Qual Health Care ; 35(4)2023 Dec 29.
Artículo en Inglés | MEDLINE | ID: mdl-38157269

RESUMEN

Lean healthcare visual management has been successfully integrated into infection control programs, leading to lower healthcare-associated infection (HAI) rates and greater provider compliance with evidence-based prevention practices; however, its implementation during quality improvement (QI) initiatives in limited-resource settings has not yet been well exploited. We aimed to describe a low-cost strategy involving Kamishibai cards to sustain bundles' adherence to prevent HAIs in a middle-income country. This descriptive case study evaluated the implementation of a lean healthcare visual management tool-Kamishibai board (K-board)-during a nationwide QI collaborative preventing three critical HAIs in 189 adult and pediatric/neonatal intensive care units (ICUs) from September 2021 to January 2023. Considering a limited-resource setting, our team adapted a K-board using simple, cheap, and easy-to-handle materials for routine monitoring of QI procedures, including safety bundles' compliance. After test prototypes, the final K-board version was implemented. The chart materials and assembly cost BRL 80.00 (USD 15.48). Before launching, expert working group meetings were held to shape the contents, refine technical issues, and prepare the ICU teams for implementation. After starting, plan-do-study-act cycles were conducted according to the Breakthrough Series model. Participating ICU teams, including leaders and front-line health workers, performed bedside audits following a weekly chronogram. Two indicators were calculated: the percentage of ICUs in which K-boards were being implemented and whether bundles' compliance was addressed in the K-board. Audit data were recorded in 'SimpleQI'. After 17 months of this initiative, 177 (93.7%) participating ICUs had included this visual management tool in their daily care routines. When more than 94 (>50%) ICUs posted K-board data, the mean compliance for the bundles for each HAI was sustained above 85%. A lean healthcare visual management tool can be adapted to local settings, including healthcare facilities with limited resources. K-board seems to be a feasible method for auditing evidence-based practices in medical care, including safety bundles to simultaneously prevent three types of HAIs.


Asunto(s)
Infecciones Relacionadas con Catéteres , Infección Hospitalaria , Niño , Recién Nacido , Adulto , Humanos , Infección Hospitalaria/prevención & control , Control de Infecciones/métodos , Unidades de Cuidados Intensivos , Unidades de Cuidado Intensivo Neonatal , Adhesión a Directriz , Atención a la Salud , Infecciones Relacionadas con Catéteres/prevención & control
15.
Clin Oral Investig ; 27(12): 7919-7933, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38032392

RESUMEN

AIM: To evaluate the bond strength (BS) and analysis of the adhesive interface in root canals filled with bioceramic gutta percha sealers and cones. MATERIAL AND METHODS: Ninety-six maxillary canines were divided into eight groups according to the endodontic sealer (AH Plus, AH Plus Bioceramic, Bio-C Sealer or Bio-C Sealer Ion+ and gutta percha cones (conventional or bioceramic) tested. They were analyzed using the BS test, failure pattern, analysis of the adhesive interface by scanning electron microscopy and confocal laser scanning microscopy. The BS data were compared between groups using the analysis of variance test with the Turkey post-test. The chi-square test was used to assess the type of failure and the non-parametric Mann-Whitney and Kruse-Wallis tests (P < 0.05). RESULTS: Analysis of variance showed higher BS values for the groups of bioceramic gutta percha cones in Bio-C Sealer Ion+ (8.38 ± 4.27), AH Plus Bioceramic (6.19 ± 3.28), Bio-C Sealer (5.70 ± 3.18), AH Plus (4.61 ± 2.11) and for conventional gutta percha cones in AH Plus sealers (4.26 ± 2.35), Bio-C Sealer Ion + (3.63 ± 2.29), Bio-C Sealer (2.94 ± 2.32) and AH Plus Bioceramic (1.19 ± 0.89) (P < 0.05). Relative to the type of failure and adaptation of the types of filling material, a higher percentage of mixed failures was observed (gaps between 1 µm-10 µm) for the group with bioceramic gutta percha cones (P < 0.001). CONCLUSION: The bond between sealers and bioceramic gutta percha cones showed higher bond strength values and greater penetration into the dentin tubules. CLINICAL RELEVANCE: The filling the root canal system with bioceramic sealers should be associated with bioceramic gutta percha cones.


Asunto(s)
Gutapercha , Materiales de Obturación del Conducto Radicular , Gutapercha/química , Materiales de Obturación del Conducto Radicular/química , Resinas Epoxi/química , Cavidad Pulpar , Cementos Dentales , Obturación del Conducto Radicular , Ensayo de Materiales
16.
J Vasc Bras ; 22: e20230052, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38021275

RESUMEN

Chronic kidney disease is a worldwide public health problem, and end-stage renal disease requires dialysis. Most patients requiring renal replacement therapy have to undergo hemodialysis. Therefore, vascular access is extremely important for the dialysis population, directly affecting the quality of life and the morbidity and mortality of this patient population. Since making, managing and salvaging of vascular accesses falls within the purview of the vascular surgeon, developing guideline to help specialists better manage vascular accesses for hemodialysis if of great importance. Thus, the objective of this guideline is to present a set of recommendations to guide decisions involved in the referral, evaluation, choice, surveillance and management of complications of vascular accesses for hemodialysis.


A doença renal crônica é um problema de saúde pública global e em seu estágio terminal está associada à necessidade de terapia dialítica. A grande maioria dos pacientes que necessitam realizar a terapia renal substitutiva, a fazem através da hemodiálise. Portanto, o acesso vascular é de extrema importância para a população dialítica, implicando diretamente na qualidade de vida e na morbimortalidade deste grupo de pacientes. Sendo a confecção, gerenciamento e resgate dos acessos vasculares uma das áreas de atuação do cirurgião vascular, é de grande importância a elaboração de uma diretriz que oriente o especialista no manejo mais adequado do acesso vascular para hemodiálise. Assim, o objetivo desta diretriz é apresentar um conjunto de recomendações para guiar as decisões na referenciação, avaliação, escolha, vigilância e gestão das complicações do acesso vascular para hemodiálise.

17.
FASEB J ; 35(7): e21685, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34085343

RESUMEN

Leucine zipper-EF-hand containing transmembrane protein 1 (Letm1) is a mitochondrial inner membrane protein involved in Ca2+ and K+ homeostasis in mammalian cells. Here, we demonstrate that the Letm1 orthologue of Trypanosoma cruzi, the etiologic agent of Chagas disease, is important for mitochondrial Ca2+ uptake and release. The results show that both mitochondrial Ca2+ influx and efflux are reduced in TcLetm1 knockdown (TcLetm1-KD) cells and increased in TcLetm1 overexpressing cells, without alterations in the mitochondrial membrane potential. Remarkably, TcLetm1 knockdown or overexpression increases or does not affect mitochondrial Ca2+ levels in epimastigotes, respectively. TcLetm1-KD epimastigotes have reduced growth, and both overexpression and knockdown of TcLetm1 cause a defect in metacyclogenesis. TcLetm1-KD also affected mitochondrial bioenergetics. Invasion of host cells by TcLetm1-KD trypomastigotes and their intracellular replication is greatly impaired. Taken together, our findings indicate that TcLetm1 is important for Ca2+ homeostasis and cell viability in T cruzi.


Asunto(s)
Proteínas de Unión al Calcio/metabolismo , Calcio/metabolismo , Diferenciación Celular , Enfermedad de Chagas/parasitología , Mitocondrias/metabolismo , Proteínas Protozoarias/metabolismo , Trypanosoma cruzi/crecimiento & desarrollo , Animales , Transporte Biológico , Proteínas de Unión al Calcio/antagonistas & inhibidores , Proteínas de Unión al Calcio/genética , Chlorocebus aethiops , Metabolismo Energético , Potencial de la Membrana Mitocondrial , Proteínas Protozoarias/antagonistas & inhibidores , Proteínas Protozoarias/genética , Trypanosoma cruzi/metabolismo , Células Vero
18.
Pain Med ; 23(11): 1875-1881, 2022 10 29.
Artículo en Inglés | MEDLINE | ID: mdl-35511153

RESUMEN

INTRODUCTION: Greater trochanteric pain syndrome may often mimic pain generated from other sources. However, it is most commonly caused by gluteus medius and gluteus minimus tendinopathy or tear. The purpose of this technical report was to: 1) describe the ultrasound-guided fascial plane block technique targeting the superior gluteal nerve in the plane between gluteus medius/gluteus minimus to treat moderate-to-severe, chronic, refractory greater trochanteric pain syndrome; 2) anatomically correlate the procedure with cadaveric dissections demonstrating the structures being imaged and the tissues along the needle trajectory; 3) demonstrate the feasibility of the technique with serial dissection of one cadaveric specimen following injection with color dye. TECHNIQUE DESCRIPTION: The ultrasound-guided fascial plane block targeting the superior gluteal nerve to treat moderate-to-severe, chronic, refractory greater trochanteric pain syndrome has been outlined with supporting ultrasound scans and anatomical dissections. The cadaveric dissections are correlated to the ultrasound scans of a healthy volunteer and provide visualization of the tissues in the needle trajectory. The feasibility study in a cadaveric specimen showed adequate stain of the superior gluteal nerve without spread to the piriformis muscle belly, the sciatic nerve, or the inferior gluteal nerve. CONCLUSIONS: This ultrasound-guided fascial plane block is a feasible option for blocking the superior gluteal nerve without inadvertent involvement of the sciatic and inferior gluteal nerves. Further randomized controlled clinical trials are necessary to assess the clinical efficacy of the gluteus medius/gluteus minimus fascial plane block to treat moderate-to-severe, chronic, refractory greater trochanteric pain syndrome.


Asunto(s)
Bursitis , Humanos , Correlación de Datos , Dolor , Ultrasonografía Intervencional , Cadáver
19.
Mar Drugs ; 20(2)2022 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-35200640

RESUMEN

Schistosomiasis has been controlled for more than 40 years with a single drug, praziquantel, and only one molluscicide, niclosamide, raising concern of the possibility of the emergence of resistant strains. However, the molecular targets for both agents are thus far unknown. Consequently, the search for lead compounds from natural sources has been encouraged due to their diverse structure and function. Our search for natural compounds with potential use in schistosomiasis control led to the identification of an algal species, Laurencia dendroidea, whose extracts demonstrated significant activity toward both Schistosoma mansoni parasites and their intermediate host snails Biomphalaria glabrata. In the present study, three seaweed-derived halogenated sesquiterpenes, (-)-elatol, rogiolol, and obtusol are proposed as potential lead compounds for the development of anthelminthic drugs for the treatment of and pesticides for the environmental control of schistosomiasis. The three compounds were screened for their antischistosomal and molluscicidal activities. The screening revealed that rogiolol exhibits significant activity toward the survival of adult worms, and that all three compounds showed activity against S. mansoni cercariae and B. glabrata embryos. Biomonitored fractioning of L. dendroidea extracts indicated elatol as the most active compound toward cercariae larvae and snail embryos.


Asunto(s)
Antihelmínticos , Laurencia , Moluscocidas , Sesquiterpenos , Animales , Antihelmínticos/aislamiento & purificación , Antihelmínticos/farmacología , Larva , Laurencia/química , Moluscocidas/aislamiento & purificación , Moluscocidas/farmacología , Schistosoma mansoni/efectos de los fármacos , Esquistosomiasis/tratamiento farmacológico , Sesquiterpenos/aislamiento & purificación , Sesquiterpenos/farmacología , Compuestos de Espiro/aislamiento & purificación , Compuestos de Espiro/farmacología
20.
Clin Oral Investig ; 26(8): 5105-5116, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35618962

RESUMEN

AIM: To evaluate the influence of root canal filling quality on periapical lesion status using cone-beam computed tomography (CBCT). MATERIALS AND METHODS: The bibliographic search was conducted in electronic databases of PubMed, Embase, Scopus, and Web of Science without restrictions related to the year of publication and language. Inclusion criteria were prospective or retrospective cohort studies that followed periapical pathosis for, at least, 1 year. Three reviewers independently evaluated the eligibility for inclusion, extracted data, and assessed the risk of bias. The quality of the studies was based on the Newcastle-Ottawa Scale. This meta-analysis was performed to evaluate the quality of treatment by the homogeneity and apical extension of the filling. RESULTS: Of the 1179 studies initially recovered, six cohort studies were included, out of which four were considered with a low risk of bias. The results showed that the absence of gaps in the filling reduced the chance of unhealed periapical lesions by 2.39 times (RR = 2.39; 95% CI: 1.62-3.53; p < 0.00001; I2 = 55%). An apical filling extension of 0-2 mm below the apex also contributed significantly to the absence of unhealed periapical lesions (RR = 1.49; 95% CI: 1.15-1.94; p = 0.003; I2 = 2%). CONCLUSION: The homogeneity and apical extension of the filling influenced the presence of unhealed periapical lesions in endodontically treated teeth evaluated using CBCT. CLINICAL RELEVANCE: Apical extension of the filling ranging between 0 and 2 mm short of the apical foramen and the homogeneity of the filling without gaps are directly related to the success rate of root canal treatment.


Asunto(s)
Cavidad Pulpar , Periodontitis Periapical , Tomografía Computarizada de Haz Cónico/métodos , Humanos , Periodontitis Periapical/terapia , Estudios Prospectivos , Estudios Retrospectivos , Tratamiento del Conducto Radicular/métodos
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