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1.
EMBO Rep ; 22(1): e50615, 2021 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-33185004

RESUMO

The retinoblastoma tumour suppressor protein (RB) regulates a number of diverse cellular functions including differentiation, angiogenesis, chromatin remodelling, senescence and apoptosis. The best-characterised function of RB is cell cycle regulation, and it has been considered a phosphoprotein regulated by cyclin-dependent kinases. In its hypophosphorylated form, RB binds the transcription factor E2F1, arresting the cell cycle in the G1 phase. Here, we show that MDM2 controls the cell cycle through synthesis and degradation of RB protein in a cell cycle condition-dependent fashion. MDM2 induces G1 cell cycle arrest by enhancing the translation of the RB mRNA under genotoxic stress. Translation requires direct interaction between the RB mRNA and the MDM2 protein that accompanies the RB mRNA to the polysomes. However, MDM2 ubiquitinates and degrades RB protein at the G2/M phase under genotoxic stress. The ATM phosphomimetic mutant MDM2(S395D) corroborates that the effect on the RB levels is dependent on the DNA damage. These results provide the basis of a dual regulatory mechanism by which MDM2 controls cell cycle progression during DNA damage.


Assuntos
Ciclo Celular , Dano ao DNA , Proteínas Proto-Oncogênicas c-mdm2 , Proteína do Retinoblastoma , Ciclo Celular/genética , Fosforilação , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Proteína do Retinoblastoma/genética , Proteína do Retinoblastoma/metabolismo
2.
Scand J Gastroenterol ; 57(1): 124-130, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34669534

RESUMO

BACKGROUND/AIMS: The effectiveness of screening esophagogastroduodenoscopy (EGD) for refractory gastroesophageal reflux disease (GERD) symptoms alone has not been validated. METHODS: We performed an observational study of patients with refractory GERD who underwent EGD from 2013 to 2016 at a tertiary hospital. Among 928 patients with GERD, we excluded patients with other alarm features, other indications for EGD, history of gastroesophageal surgery, or EGD done for other diagnostic procedures, and identified 301 patients who underwent EGD solely for persistent reflux symptoms such as heartburn or regurgitation. RESULTS: Among 301 patients with refractory GERD, 81.4% of patients were taking PPIs. 49.8% of patients had completely normal EGD findings and 33.6% of patients had benign or incidental findings. Two patients (0.6%) had LA grade C or D esophagitis, and 16.3% of patients had irregular Z line or salmon-colored mucosa. 91.0% (122/134) who had a biopsy had normal or benign findings. 4.0% (12/301) of patients had biopsy-proven intestinal metaplasia which is similar to the previously known prevalence of intestinal metaplasia in patients without heartburn (5.6%) and none had dysplasia or malignancy. Male sex was associated with endoscopic intestinal metaplasia suspected lesions in multivariate analysis (OR: 1.96, 95% CI: 1.04-3.70, p = .036) but not biopsy-proven intestinal metaplasia. Elderly age, obesity, alcohol or cigarette consumption, PPI use, GERD duration >3-5 years did not predict endoscopically suspected or biopsy-proven intestinal metaplasia. Only 5% of patients had a pH-impedance study for refractory reflux symptoms. CONCLUSIONS: Most patients who underwent EGD for refractory GERD symptoms alone did not have pathological findings requiring a change in management. Screening EGD for patients only with persistent reflux symptoms should not be routinely recommended.


Assuntos
Refluxo Gastroesofágico , Idoso , Pré-Escolar , Endoscopia do Sistema Digestório/métodos , Refluxo Gastroesofágico/complicações , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/tratamento farmacológico , Azia/etiologia , Humanos , Masculino , Inibidores da Bomba de Prótons/uso terapêutico , Resultado do Tratamento
4.
JAMA Ophthalmol ; 142(3): 243-247, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38358749

RESUMO

Importance: Strabismus is a common ocular disorder of childhood. There is a clear genetic component to strabismus, but it is not known if esotropia and exotropia share genetic risk factors. Objective: To determine whether genetic duplications associated with esotropia are also associated with exotropia. Design, Setting, and Participants: This was a cross-sectional study conducted from November 2005 to December 2023. Individuals with constant or intermittent exotropia of any magnitude or a history of surgery for exotropia were recruited from pediatric ophthalmic practices. Data were analyzed from March to December 2023. Exposure: Genetic duplication. Main Outcomes and Measures: Presence of genetic duplications at 2p11.2, 4p15.2, and 10q11.22 assessed by digital droplet polymerase chain reaction. Orthoptic measurements and history of strabismus surgery were performed. Results: A total of 234 individuals (mean [SD] age, 19.5 [19.0] years; 127 female [54.3%]) were included in this study. The chromosome 2 duplication was present in 1.7% of patients with exotropia (4 of 234; P = .40), a similar proportion to the 1.4% of patients with esotropia (23 of 1614) in whom it was previously reported and higher than the 0.1% of controls (4 of 3922) previously reported (difference, 1.6%; 95% CI, 0%-3.3%; P < .001). The chromosome 4 duplication was present in 3.0% of patients with exotropia (7 of 234; P = .10), a similar proportion to the 1.7% of patients with esotropia (27 of 1614) and higher than the 0.2% of controls (6 of 3922) in whom it was previously reported (difference, 2.8%; 95% CI, 0.6%-5.0%; P < .001). The chromosome 10 duplication was present in 6.0% of patients with exotropia (14 of 234; P = .08), a similar proportion to the 4% of patients with esotropia (64 of 1614) and higher than the 0.4% of controls (18 of 3922) in whom it was previously reported (difference, 5.6%; 95% CI, 2.5%-8.6%; P < .001). Individuals with a duplication had higher mean (SD) magnitude of deviation (31 [13] vs 22 [14] prism diopters [PD]; difference, 9 PD; 95% CI, 1-16 PD; P = .03), were more likely to have constant (vs intermittent) exotropia (70% vs 29%; difference, 41%; 95% CI, 20.8%-61.2%; P < .001), and had a higher rate of exotropia surgery than those without a duplication (58% vs 34%; difference, 24%; 95% CI, 3%-44%; P = .02). Conclusions and Relevance: In this cross-sectional study, results suggest that the genetic duplications on chromosomes 2, 4, and 10 were risk factors for exotropia as well as esotropia. These findings support the possibility that esotropia and exotropia have shared genetic risk factors. Whether esotropia or exotropia develops in the presence of these duplications may be influenced by other shared or independent genetic variants or by environmental factors.


Assuntos
Esotropia , Exotropia , Estrabismo , Humanos , Criança , Feminino , Adulto Jovem , Adulto , Esotropia/genética , Esotropia/cirurgia , Exotropia/genética , Estudos Transversais , Variações do Número de Cópias de DNA , Músculos Oculomotores/cirurgia , Genótipo , Fenótipo
5.
J Clin Gastroenterol ; 47(10): 857-60, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23632349

RESUMO

BACKGROUND: Oblique-viewing echoendoscopes may miss luminal lesions. There is no consensus on whether to routinely perform esophagogastroduodenoscopy (EGD) before endoscopic ultrasonography (EUS). Currently, practice patterns are variable and prospective data are needed. AIM: : To determine the proportion of clinically meaningful lesions detected when EGD is performed routinely before EUS. STUDY: This was a multicenter prospective cohort study conducted at tertiary referral center and large community practice. Patients undergoing EUS for pancreatico-biliary and mediastinal indications were enrolled. MAIN OUTCOMES: The primary outcome was the proportion of patients with a clinically meaningful lesion found on EGD. This was a combined outcome defined as any lesion that would alter medical management, or impact the subsequent EUS examination. RESULTS: Two hundred four patients were included in the final analysis. Clinically meaningful lesions were found on EGD in 45 patients [22.1%; 95% confidence interval (CI), 16.4-27.8]. Lesions that altered medical management were found in 32 patients (15.7%; 95% CI, 10.7-20.7). Lesions impacting the subsequent EUS examination were found in 20 patients (9.8%; 95% CI, 5.7-13.9). Clinically meaningful lesions found were (number of patients): esophagitis (14), ulcer (9), ring/stricture (7), large hiatal hernia (6), hyperplastic gastric polyp (5), Barrett esophagus (3), surgically altered anatomy (2), neoplastic lesion (2), subepithelial mass/GIST (1), stenosis (1), diverticulum (1), and fistula (1). CONCLUSIONS: EGD before EUS may detect enough clinically meaningful lesions to support the routine performance of EGD before EUS.


Assuntos
Doenças Biliares/diagnóstico , Endoscopia do Sistema Digestório/métodos , Endossonografia/métodos , Doenças do Mediastino/diagnóstico , Pancreatopatias/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Biliares/fisiopatologia , Estudos de Coortes , Feminino , Humanos , Masculino , Doenças do Mediastino/fisiopatologia , Pessoa de Meia-Idade , Pancreatopatias/fisiopatologia , Estudos Prospectivos , Adulto Jovem
6.
Artigo em Inglês | MEDLINE | ID: mdl-38500555

RESUMO

Strabismus, or misalignment of the eyes, is the most common ocular disorder in the pediatric population, affecting approximately 2%-4% of children. Strabismus leads to the disruption of binocular vision, amblyopia, social and occupational discrimination, and decreased quality of life. Although it has been recognized since ancient times that strabismus runs in families, its inheritance patterns are complex, and its precise genetic mechanisms have not yet been defined. Family, population, and twin studies all support a role of genetics in the development of strabismus. There are multiple forms of strabismus, and it is not known if they have shared genetic mechanisms or are distinct genetic disorders, which complicates studies of strabismus. Studies assuming that strabismus is a Mendelian disorder have found areas of linkage and candidate genes in particular families, but no definitive causal genes. Genome-wide association studies searching for common variation that contributes to strabismus risk have identified two risk loci and three copy number variants in white populations. Causative genes have been identified in congenital cranial dysinnervation disorders, syndromes in which eye movement is limited or paralyzed. The causative genes lead to either improper differentiation of cranial motor neurons or abnormal axon guidance. This article reviews the evidence for a genetic contribution to strabismus and the recent advances that have been made in the genetics of comitant strabismus, the most common form of strabismus.

7.
Nutrients ; 15(21)2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37960149

RESUMO

Vegetables are an essential component of a healthy dietary pattern in children; however, their consumption is often insufficient due to lack of preference. To address this, the influence of combining vegetables (mixed peas and carrots-MPACs) with potatoes, a generally liked food, on overall vegetable consumption among children aged 7-13 years was explored. The research involved a cross-over study design with 65 participants who completed five lunchtime meal conditions, each with different combinations of MPACs and potatoes versus a control (MPACs with a wheat roll). The meals were provided in a cafeteria setting, and plate waste was used to measure vegetable consumption. Anthropometric data and other variables were also measured. Notably, self-reported hunger did not significantly differ between conditions. Meal condition was a significant predictor of MPACs (F = 5.20; p = 0.0005), with MPAC consumption highest when combined with shaped potato faces in the same bowl (+8.77 g compared to serving MPACs and shaped potato faces in separate bowls) and lowest when combined with diced potatoes in the same bowl (-2.85 g compared to serving MPACs and diced potatoes in separate bowls). The overall model for MPAC consumption was influenced by age, height z-score, body fat percentage z-score, and condition (likelihood ratio = 49.1; p < 0.0001). Age had the strongest correlation with vegetable consumption (r = 0.38), followed by male gender, height z-score (r = 0.30), and body fat z-score (r = -0.15). The results highlight the positive impact of combining potatoes with vegetables in school meals, particularly when using shaped potato faces. These findings emphasize the potential of potatoes as a valuable vegetable option in promoting healthier eating habits among children. Additionally, future research could explore the impact of different potato combinations and investigate other factors influencing meal consumption in school settings.


Assuntos
Solanum tuberosum , Verduras , Criança , Humanos , Masculino , Estudos Cross-Over , Dieta , Comportamento Alimentar , Frutas , Feminino , Adolescente
8.
Hepatology ; 53(4): 1377-87, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21480339

RESUMO

Recent progress in understanding the molecular mechanisms of bile formation and cholestasis have led to new insights into the pathogenesis of drug-induced cholestasis. This review summarizes their variable clinical presentations, examines the role of transport proteins in hepatic drug clearance and toxicity, and addresses the increasing importance of genetic determinants, as well as practical aspects of diagnosis and management.


Assuntos
Colestase/induzido quimicamente , Proteínas de Transporte/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Colestase/metabolismo , Colestase/fisiopatologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Hepatopatias/metabolismo
9.
FEBS J ; 289(15): 4371-4382, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-34042282

RESUMO

The retinoblastoma gene (RB1) was the first tumour suppressor cloned; the role of its protein product (RB) as the principal driver of the G1 checkpoint in cell cycle control has been extensively studied. However, many other RB functions are continuously reported. Its role in senescence, DNA repair and apoptosis, among others, is indications of the significance of RB in a vast network of cellular interactions, explaining why RB loss or its malfunction is one of the leading causes of a large number of paediatric and adult cancers. RB was first reported in retinoblastoma, a common intraocular malignancy in the paediatric population worldwide. Currently, its diagnosis is clinical, and in nondeveloped countries, where the incidence is higher, it is performed in advanced stages of the disease, compromising the integrity of the eye and the patient's life. Even though new treatments are being continuously developed, enucleation is still a major choice due to the late disease stage diagnosis and treatments costs. Research into biomarkers is our best option to improve the chances of good results in the treatment and hopes of patients' good quality of life. Here, we recapitulated the history of the disease and the first treatments to put the advances in its clinical management into perspective. We also review the different functions of the protein and the progress in the search for biomarkers. It is clear that there is still a long way to go, but we should offer these children and their families a better way to deal with the disease with the community's effort.


Assuntos
Neoplasias da Retina , Retinoblastoma , Adulto , Criança , Genes Supressores de Tumor , Humanos , Qualidade de Vida , Neoplasias da Retina/diagnóstico , Neoplasias da Retina/genética , Neoplasias da Retina/terapia , Retinoblastoma/diagnóstico , Retinoblastoma/genética , Retinoblastoma/terapia , Proteína do Retinoblastoma/genética
10.
Neurogastroenterol Motil ; 34(3): e14233, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34532898

RESUMO

BACKGROUND AND AIMS: Chronic opioid effects on the esophagus are poorly understood. We investigated whether opioids were associated with increased prevalence of esophageal motility disorders. METHODS: A retrospective study of all patients undergoing high-resolution manometry (HREM) at the Yale Gastrointestinal Motility Lab between January 2014 and August 2019. Data were extracted from the electronic medical record after studies were reviewed by two motility specialists using the Chicago Classification v.3.0. We compared the manometric results of patients who use opioids to those who do not and adjusted for type and dose of opioids using a 24 h Morphine Milligram Equivalents (MME) scale to compare patients taking low or high amounts of opioids. RESULTS: Four manometric abnormalities were significantly different between the opioid and non-opioid users. Achalasia type III, esophagogastric junction outflow obstruction (EGJOO), and distal esophageal spasm (DES) (p < 0.005, p < 0.01, and p < 0.005, respectively) were common among opioid users, whereas ineffective esophageal motility (IEM) was more common among non-opioid users (p < 0.01). The incidence of EGJOO was significantly higher in opioid users compared to non-opioid users (p < 0.001). Lastly, IRP, DCI, and distal latency were significantly different between the two groups. Patients in the high MME group had significantly greater IRP, DCI, and lower distal latency than non-opioids (p < 0.001). Also, achalasia type III and DES were more common in the high but not the low MME group. CONCLUSIONS: Opioid use is associated with multiple abnormalities on esophageal motility and these effects may be dose-dependent.


Assuntos
Acalasia Esofágica , Transtornos da Motilidade Esofágica , Transtornos Relacionados ao Uso de Opioides , Analgésicos Opioides/efeitos adversos , Transtornos da Motilidade Esofágica/induzido quimicamente , Transtornos da Motilidade Esofágica/diagnóstico , Transtornos da Motilidade Esofágica/epidemiologia , Junção Esofagogástrica , Humanos , Manometria/métodos , Espasticidade Muscular/induzido quimicamente , Estudos Retrospectivos
11.
Nucl Med Commun ; 43(12): 1163-1170, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36266992

RESUMO

Cardiovascular diseases (CVDs) are the leading cause of mortality in Latin America and the Caribbean (LAC), with the risk in men being slightly higher than in women. The coronavirus disease 2019 (COVID-19) pandemic caused a significant reduction in the number of cardiac diagnostic procedures globally and in particular in LAC. Nuclear cardiology is available in the region, but there is variability in terms of existing technology, radiopharmaceuticals, and human resources. In the region, there are 2385 single photon emission computed tomography (SPECT) and 315 PET scanners, Argentina and Brazil have the largest number. There is an increasing number of new technologies such as cadmium-zinc-telluride (CZT) cardiac-dedicated gamma cameras, SPECT/computed tomography (CT), and PET/CT. All countries performed myocardial perfusion imaging studies, mainly gated-SPECT; the rest are multi-gated acquisition, mainly for cardiac toxicity; detection of viability; rest gated SPECT in patients with dilated cardiomyopathy, and bone-avid tracer cardiac scintigraphy for transthyretin cardiac amyloidosis diagnosis. Regarding other non-nuclear cardiac imaging modalities, Argentina, Colombia, and Chile have the highest ratio of CT scanners, while Brazil, Argentina, and Chile show the highest ratio of MRI scanners. The development of nuclear cardiology and other advanced imaging modalities is challenged by the high cost of equipment, lack of equipment maintenance and service, insufficient-specific training both for imaging specialists and referring clinicians, and lack of awareness of cardiologists or other referring physicians on the clinical applications of nuclear cardiology. Another important aspect to consider is the necessity of implementing cardiac imaging multimodality training. A joint work of nuclear medicine specialists, radiologists, cardiologists, and clinicians, in general, is mandatory to achieve this goal. National, regional, and international cooperation including support from scientific professional societies such as the American Society of Nuclear Cardiology and Latin American Association of Biology and Nuclear Medicine Societies, cardiological societies, and organizations such as the International Atomic Energy Agency, and Pan American Health Organization, as well as government commitment are key factors in the overall efforts to tackle the burden of cardiovascular diseases in the region.


Assuntos
COVID-19 , Cardiologia , Doenças Cardiovasculares , Imagem de Perfusão do Miocárdio , Masculino , Humanos , Feminino , América Latina , Doenças Cardiovasculares/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , COVID-19/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Região do Caribe
12.
J Health Care Poor Underserved ; 31(4S): 104-113, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-35061612

RESUMO

As the COVID-19 pandemic and national reckoning with racism reveal social disparities and their connection to health outcomes, we consider medical education's role in addressing pervasive health inequities and the labor of students, faculty, and community members who have come together to engage with these issues. We encourage institutions to consider a more socially-grounded model where all medical students-regardless of background, specialty, and career trajectory-participate in community-engaged and health equity-focused learning opportunities and curricula. As non-physician newcomers to medical education who are experienced in community-engaged work, in this commentary we consider how institutions might develop preclinical proximity-focused learning experiences. Reimagining academic medicine-community experiences has the potential to support medical students and community partnerships in fostering health equity in times of crisis and normalcy.

13.
PLoS One ; 15(6): e0234337, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32502182

RESUMO

Loss of retinoblastoma (RB) function in the cone cells during retina development is necessary but not sufficient for retinoblastoma development. It has been reported that in the absence of RB activity, a retinoma is generated, and the onset of retina cancer occurs until the p53 pathway is altered. Unlike other types of cancer, in retinoblastoma the p53 tumour suppressor is mostly wild type, although its two primary regulators, MDMX and MDM2, are commonly dysregulated. A mutated RB form is inherited in around 35% of the cases, but normally two, somatic mutations are needed to alter the RB function. Here we investigated the mRNA levels of RB, p53, MDMX and MDM2 in peripheral blood samples of retinoblastoma patients to monitor the pathway status of p53 in somatic cells. We sought to investigate the involvement of these genes in the development of retina cancer, with the aim of identifying biomarkers for early diagnosis of this disease.


Assuntos
Retinoblastoma/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Adulto , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Criança , Pré-Escolar , Feminino , Genes do Retinoblastoma/genética , Humanos , Lactente , Recém-Nascido , Masculino , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Retina/patologia , Células Fotorreceptoras Retinianas Cones/metabolismo , Neoplasias da Retina/patologia , Retinoblastoma/sangue , Retinoblastoma/genética , Proteína do Retinoblastoma/genética , Proteína do Retinoblastoma/metabolismo , Proteína Supressora de Tumor p53/sangue , Proteína Supressora de Tumor p53/genética
14.
J Hepatol ; 51(6): 1091-6, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19836097

RESUMO

BACKGROUNDS/AIMS: Hepatitis B virus (HBV) reactivation following treatment with rituximab has been reported in patients with either HBsAg-positive, or HBsAg-negative and anti-HBc positive infection. Patients with severe reactivation often have a fatal outcome despite treatment with lamivudine. The use of entecavir has not been reported in patients with severe HBV reactivation. METHODS: We present a case of a HBsAg-negative patient diagnosed with chronic lymphocytic leukemia who received a chemotherapeutic regimen that included rituximab, who subsequently presented with severe HBV reactivation with ascites, jaundice and coagulopathy and was treated with entecavir. A review of the literature and underlying HBV associated mutations are discussed. RESULTS: Entecavir produced a rapid and sustained suppression of HBV that was associated with rapid clinical improvement without any side effects. CONCLUSION: Entecavir is an efficacious and safe treatment for severe HBV reactivation.


Assuntos
Anticorpos Monoclonais/efeitos adversos , Antivirais/uso terapêutico , Guanina/análogos & derivados , Hepatite B/tratamento farmacológico , Anticorpos Monoclonais Murinos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Guanina/uso terapêutico , Hepatite B/complicações , Hepatite B/virologia , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/genética , Humanos , Imunossupressores/efeitos adversos , Leucemia Linfocítica Crônica de Células B/complicações , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva , Rituximab , Vidarabina/efeitos adversos , Vidarabina/análogos & derivados
15.
BMJ Case Rep ; 12(6)2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31227569

RESUMO

Annular pancreas (AP) is a rare diagnosis in the adult population but can cause significant morbidity if not correctly identified. In adults, the most common symptoms are abdominal pain, nausea and vomiting. While these are not specific to AP, they are important clues to this diagnosis in the right clinical context. We present the case of a 24-year-old woman presenting with a 6-year history of progressive abdominal pain and dyspepsia in the context of an extensive negative workup. Upper gastrointestinal (GI) series and MRI revealed partial duodenal obstruction, concerning for AP. While patients with chronic abdominal pain and vague GI complaints may be diagnosed with functional bowel disorders, it is important to appropriately address the possibility of an underlying structural lesion such as AP. This strategy is not only cost-effective but also saves the patient discomfort associated with unnecessary procedures and allows a timely intervention.


Assuntos
Dor Abdominal/etiologia , Obstrução Duodenal/diagnóstico por imagem , Pâncreas/anormalidades , Pancreatopatias/diagnóstico , Obstrução Duodenal/cirurgia , Feminino , Humanos , Laparoscopia , Pâncreas/cirurgia , Pancreatopatias/cirurgia , Resultado do Tratamento , Trato Gastrointestinal Superior/diagnóstico por imagem , Adulto Jovem
16.
ACG Case Rep J ; 6(9): e00214, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31750381

RESUMO

Graft-versus-host disease (GVHD) is a common complication of hematopoietic stem cell transplantation but can rarely occur after solid organ transplants. Small bowel and liver transplants are typically implicated, but solid organ transplant-associated GVHD has also been associated with other organs. We present a 40-year-old diabetic woman who underwent renal followed by pancreatic transplantation over a span of 21 months and ultimately developed acute classic GVHD. The diagnosis proved to be challenging in the context of confounding infections and inconclusive bone marrow and skin biopsy findings. She had multiorgan failure at the time of endoscopic confirmation and died after having minimal response to aggressive immunosuppression.

17.
Protein Sci ; 27(5): 976-986, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29524278

RESUMO

HDM2 and HDMX are two homologs essential for controlling p53 tumor suppressor activity under normal conditions. Both proteins bind different sites on the p53 N-terminus, and while HDM2 has E3 ubiquitin ligase activity towards p53, HDMX does not. Nevertheless, HDMX is required for p53 polyubiquitination and degradation, but the underlying molecular mechanism remains unclear. Alone, HDMX and HDM2 interact via their respective C-terminal RING domains but here we show that the presence of p53 induces an N-terminal interface under normal cellular conditions. This results in an increase in HDM2-mediated p53 polyubiquitination and degradation. The HDM2 inhibitor Nutlin-3 binds the N-terminal p53 binding pocket and is sufficient to induce the HDM2-HDMX interaction, suggesting that the mechanism depends on allosteric changes that control the multiprotein complex formation. These results demonstrate an allosteric interchange between three different proteins (HDMX-HDM2-p53) and help to explain the molecular mechanisms of HDM2-inhibitory drugs.


Assuntos
Proteínas Nucleares/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Ubiquitina/metabolismo , Proteínas de Ciclo Celular , Linhagem Celular , Humanos , Imidazóis/farmacologia , Proteínas Nucleares/química , Proteínas Nucleares/deficiência , Piperazinas/farmacologia , Proteínas Proto-Oncogênicas/química , Proteínas Proto-Oncogênicas/deficiência , Proteínas Proto-Oncogênicas c-mdm2/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-mdm2/deficiência , Proteína Supressora de Tumor p53/química , Ubiquitina/química , Ubiquitinação
18.
Rev. cuba. med. mil ; 52(1)mar. 2023.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1521973

RESUMO

Introducción: La calidad de vida laboral es un proceso dinámico que favorece el desarrollo humano y el bienestar de los trabajadores, cuya percepción puede determinar el compromiso con su organización. Objetivo: Determinar la relación entre la calidad de vida laboral y el compromiso con el trabajo en el personal de enfermería de un hospital público. Métodos: Estudio transversal realizado en una muestra constituida por 43 enfermeros de un servicio de emergencia, los cuales respondieron el cuestionario de calidad de vida laboral en hospitales públicos y la escala Utrecht de compromiso en el trabajo. Se estimaron frecuencias y porcentaje, medias y desviación estándar. Se utilizó la prueba de correlación de Spearman. Resultados: Los enfermeros presentaron un buen nivel de compromiso en el trabajo (4,70 ± 0,99), la dedicación fue la dimensión mejor valorada, seguida del vigor (4,74 ± 0,85) y absorción (4,59 ± 1,35). La calidad de vida laboral media fue alta (2,18 ± 0,34). El bienestar logrado a través del trabajo fue la dimensión mejor valorada. El compromiso en el trabajo y la calidad de vida laboral tuvieron una relación significativa (rho= 0,875; p≤ 0,001). Conclusiones: La calidad de vida laboral en el personal de enfermería tiene una relación directa y alta con el compromiso.


Introduction: The quality of working life is a dynamic process that favors human development and the well-being of workers, whose perception can determine the commitment to their organization. Objective: To determine the relationship between the quality of working life and the engagement in the nursing staff of a public hospital. Methods: Cross-sectional study carried out in a sample of 43 nurses from an emergency department, who answered the questionnaire of quality of working life in public hospitals and the Utrecht scale of commitment at work. Frequencies and percentage, means and standard deviation were estimated. The Spearman correlation test was used. Results: Nurses presented a good level of commitment at work (4.70 ± 0.99), dedication was the best valued dimension, followed by vigor (4.74 ± 0.85) and absorption (4.59 ± 1.35). The mean quality of working life was high (2.18 ± 0.34). The well-being achieved through work was the dimension best valued. Work engagement and quality of working life had a significant relationship (rho= 0.875; p≤ 0.001). Conclusions: The quality of working life in the nursing staff had a direct and high relationship with engagement.

19.
Rev. cuba. oftalmol ; 35(1): e1195, ene.-mar. 2022. tab
Artigo em Espanhol | LILACS, CUMED | ID: biblio-1409028

RESUMO

Objetivo: Relacionar el tipo y profundidad de la ambliopía con el tipo y magnitud del defecto refractivo. Métodos: Estudio transversal en 27 pacientes entre cinco y 18 años con ambliopía refractiva atendidos por vez primera en la consulta de Oftalmología Pediátrica y Estrabismo del Instituto Cubano de Oftalmología Ramón Pando Ferrer. Resultados: La edad en que fueron examinados por primera vez fue similar en ambos tipos de ambliopía, pero ligeramente mayor en la ambliopía anisometrópica (media ocho años). Se halló una correlación significativa entre el nivel de profundidad de la ambliopía y la magnitud del defecto refractivo, en el ojo derecho (p = 0,001), no siendo así en el ojo izquierdo (p = 0 ,304). Conclusiones: En el grupo de estudio la edad en que son examinados se considera tardía y no existen diferencias en cuanto a género y color de piel. Existe un ligero predominio de la ambliopía isoametrópica sobre la anisometrópica, predominando el ojo izquierdo en la ambliopía anisometrópica. El defecto refractivo que se asocia con más frecuencia a la ambliopía refractiva es el astigmatismo en contra de la regla. A medida que aumenta la magnitud del defecto refractivo aumenta la profundidad de la ambliopía en el ojo derecho, no siendo así en el ojo izquierdo(AU)


Objective: To relate the type and depth of amblyopia with the type and magnitude of refractive error. Methods: Cross-sectional study carried out in 27 patients aged 5-18 years with refractive amblyopia first treated in the pediatric ophthalmology and strabismus consultation of Ramón Pando Ferrer Cuban Institute of Ophthalmology. Results: The age at which the patients were first examined was similar in both types of amblyopia, but slightly higher in anisometropic amblyopia (mean of 8 years). A significant correlation was found between the depth of amblyopia and the magnitude of the refractive error in the right eye (P=0.001), not being so in the left eye (P=0.304). Conclusions: In the study group, the age at which they are examined is considered late and there are no differences in gender or skin color. There is a slight predominance of isometropic amblyopia over anisometropic amblyopia, with a predominance of the left eye in anisometropic amblyopia. The refractive error most frequently associated with refractive amblyopia is against-the-rule astigmatism. As the magnitude of the refractive error increases, the depth of amblyopia increases in the right eye, but not in the left eye(AU)


Assuntos
Humanos , Erros de Refração , Astigmatismo , Ambliopia , Estudos Transversais
20.
Rev. Eugenio Espejo ; 16(1): 39-49, 20220111.
Artigo em Espanhol | LILACS | ID: biblio-1352995

RESUMO

La hepatopatía crónica más prevalente en el mundo es la esteatosis hepática no alcohólica. Así, se realizó una investigación con el objetivo de determinar los factores asociados a esa patología en pacientes atendidos en el Centro de salud tipo B Chambo, Ecuador, durante 2020. Se realizó un estudio con enfoque cuantitativo, de tipo no experimental, correlacional y retrospectivo. Las historias clínicas seleccionadas aportaron los datos de las variables de interés. La media de la edad de los involucrados fue de 54,43 ± 8,10 años. El 60,38% tenía hipertensión arterial, el 52,83% diabetes mellitus, el 62,26% sobrepeso u obesidad y el 49,06% dislipidemia, determi-nando que estas comorbilidades tuvieron una relación significativa con la enfermedad objeto de estudio, la que resultó más incidente en edades mayores de 50 años. Las personas sedentarias o con bajos niveles de actividad física mostraron de ALT y AST.


The most prevalent chronic liver disease in the world is nonalcoholic fatty liver disease. Thus, research aimed to determine the factors associated with this pathology in patients treated at the Type B Chambo Health Center, Ecuador, during 2020. A study was carried out with a quantitati-ve, non-experimental, correlational, and retrospective approach. The selected medical records provided the information for the variables of interest. The mean age of the population was 54.43 ± 8.10 years of age. 60.38% had arterial hypertension, 52.83% diabetes mellitus, 62.26% overweight or obesity and 49.06% dyslipidemia. It was determined that these comorbidities had a significant relationship with the disease under study, which was more incident in ages older than 50. Sedentary people or those ones with low levels of physical activity showed ALT and AST.


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Comorbidade , Fatores Abióticos , Hepatopatias , Exercício Físico , Colesterol , Sobrepeso
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