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1.
Diseases ; 12(5)2024 May 08.
Article in English | MEDLINE | ID: mdl-38785751

ABSTRACT

BACKGROUND: Appendiceal neuroendocrine tumors (NETs) rank as the third most frequent neoplasm affecting the appendix, originating from enterochromaffin cells. This study aims to evaluate the influence of various prognostic factors on the mortality rates of patients diagnosed with NETs of the appendix. METHODS: Conducted retrospectively, the study involved 3346 patients, utilizing data sourced from the Surveillance, Epidemiology, and End Results (SEER) database. Our analysis centered on investigating demographic characteristics, clinical features, overall mortality (OM), and cancer-specific mortality (CSM) among the cohort. Variables showing a p-value < 0.1 in the univariate Cox regression were incorporated into the multivariate Cox regression analysis. A Hazard Ratio (HR) > 1 indicated an unfavorable prognosis. RESULTS: In the multivariate analysis, higher OM and CSM were observed in males, older age groups, tumors with distant metastasis, poorly differentiated tumors, and those who underwent chemotherapy. Non-Hispanic Black individuals showed elevated mortality rates. CONCLUSION: Delayed diagnosis may contribute to the increased mortality in this community. Improved access to healthcare and treatment is crucial for addressing these disparities. Larger prospective studies are needed to pinpoint the underlying causes of elevated mortality in non-Hispanic Black populations, and randomized controlled trials (RCTs) are warranted to evaluate therapies for advanced-stage appendix NETs.

2.
Health Aff (Millwood) ; 40(11): 1784-1791, 2021 11.
Article in English | MEDLINE | ID: mdl-34724418

ABSTRACT

Racial health inequities exemplified during the COVID-19 crisis have awakened a sense of urgency among public health and policy experts to examine contributing factors. One potential factor includes the socioeconomic disadvantage of racially segregated neighborhoods. This study quantified associations of neighborhood socioeconomic disadvantage in Chicago, Illinois, as measured by the Area Deprivation Index (ADI), with racial disparities in COVID-19 positivity. A retrospective cohort included 16,684 patients tested for COVID-19 at an academic medical center and five community-based testing sites during Chicago's "first wave" (March 12, 2020-June 25, 2020). Patients living in Black majority neighborhoods had two times higher odds of COVID-19 positivity relative to those in White majority neighborhoods. The ADI accounted for 20 percent of the racial disparity; however, COVID-19 positivity remained substantially higher at every decile of the ADI in Black relative to White neighborhoods. The remaining disparities (80 percent) suggest a large, cumulative effect of other structural disadvantages in urban communities of color.


Subject(s)
COVID-19 , Chicago/epidemiology , Humans , Racial Groups , Residence Characteristics , Retrospective Studies , SARS-CoV-2 , Socioeconomic Factors
3.
Science ; 372(6538)2021 04 09.
Article in English | MEDLINE | ID: mdl-33833093

ABSTRACT

DNA methylation is essential to mammalian development, and dysregulation can cause serious pathological conditions. Key enzymes responsible for deposition and removal of DNA methylation are known, but how they cooperate to regulate the methylation landscape remains a central question. Using a knockin DNA methylation reporter, we performed a genome-wide CRISPR-Cas9 screen in human embryonic stem cells to discover DNA methylation regulators. The top screen hit was an uncharacterized gene, QSER1, which proved to be a key guardian of bivalent promoters and poised enhancers of developmental genes, especially those residing in DNA methylation valleys (or canyons). We further demonstrate genetic and biochemical interactions of QSER1 and TET1, supporting their cooperation to safeguard transcriptional and developmental programs from DNMT3-mediated de novo methylation.


Subject(s)
DNA Methylation , DNA/metabolism , Human Embryonic Stem Cells/metabolism , CRISPR-Cas Systems , DNA (Cytosine-5-)-Methyltransferases/metabolism , DNA Methyltransferase 3A , Enhancer Elements, Genetic , Gene Expression Regulation, Developmental , Gene Knock-In Techniques , Gene Knockout Techniques , Genome, Human , Humans , Mixed Function Oxygenases/genetics , Mixed Function Oxygenases/metabolism , Promoter Regions, Genetic , Protein Binding , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins/metabolism , Transcription, Genetic , DNA Methyltransferase 3B
4.
Rev. méd. Hosp. José Carrasco Arteaga ; 12(2): 112-118, 31-07-2020. Tablas, Gráficos
Article in Spanish | LILACS | ID: biblio-1178984

ABSTRACT

INTRODUCCIÓN: La apendicitis aguda (AA) es la principal causa de abdomen agudo no traumático en el mundo, continúa siendo un problema de salud pública y su diagnóstico aún es desafiante. Ante los cuadros atípicos es necesario apoyarse con la utilización de escalas o scores diagnósticos, los más estudiados son la Escala de Alvarado, Escala de Alvarado Modificada, RIPASA entre otras. El objetivo de este estudio fue determinar la validez de la Escala de Respuesta Inflamatoria versus la Escala de Alvarado, para el diagnóstico de apendicitis aguda en pacientes de 16 años y más de edad. MATERIALES Y MÉTODOS: Estudio transversal, observacional, de validación de pruebas diagnósticas, entre las escalas AIR y Alvarado, con el resultado de anatomía patológica como Gold estándar. Con una muestra de 292 pacientes apendicectomizados en el hospital José Carrasco Arteaga durante el 2018. Para el análisis estadístico se obtuvo la sensibilidad, especificidad, VPP y VPN, curva ROC y Razón de Verosimilitud. RESULTADOS: El 49.7% de pacientes correspondieron al grupo etario de adultos jóvenes, con predominio del sexo masculino (62.7%). La Escala de Alvarado presentó una sensibilidad de 88.5%, especificidad de 29.6%, VPP de 81.7% y VPN de 42.2%, un LR + de 1.23 y un LR ­ de 0.38; en comparación con los registrados para la Escala AIR de 94.7% (sensibilidad), 76.5% (especificidad), VPP 93.5%, VPN de 80.3%, LR + de 4.02 y un LR ­ de 0.07. La curva ROC de la AIRS fue de 0.897, superior a la de Alvarado de 0.611; confiriendo a la primera escala mayor precisión diagnóstica. CONCLUSIÓN: La escala de Respuesta Inflamatoria en Apendicitis (AIR) mostró una mayor sensibilidad de 94.7% y especificidad de 76.5%, mientras que la escala de Alvarado mostró sensibilidad de 88.5% y especificidad de 29.6%. La escala de Alvarado es una herramienta lo suficientemente sensible para diagnosticar apendicitis aguda, pero no es específica para excluirla. La escala AIR presenta un valor de verosimilitud y una Curva ROC mayor a la de Alvarado, sin embargo, presenta una probabilidad post test baja al momento de identificar a los casos de apendicitis aguda.(au)


BACKGROUND: Acute appendicitis is the main cause of non-traumatic acute abdomen worldwide, it is still a public health issue and the diagnosis can be challenging. When an atypical case is presented, is necessary to use diagnostic scores, like Alvarado Score, Modified Alvarado Score, RIPASA, among others. The aim of this study was to determine the test validity of Inflammatory Response Score versus Alvarado Score, for acute appendicitis diagnosis in 16 year old and older patients. METHODS: This is a descriptive, cross-sectional, validity test study, to compare AIR Score and Alvarado Score, with the Gold-Standard histopathology results. A sample of 292 patients that went under appendectomy at Hospital José Carrasco Arteaga during 2018 was studied. We considered sensitivity, specificity, positive predictive value (PPV), negative predictive value (VPN), ROC curve and Likelihood Ratio. RESULTS: 49.7% patients were young adults, 62.7% of the patients were male. Alvarado Score showed a 88.5% sensitivity, 29.6% specificity, PPV of 81.7%, 42.2% NPV, 1.23 LR+ and 0.38 ­LR; compared to 94.7% sensitivity, 76.5% specificity, 93.5% PPV, 80.3% NPV, 4.02 +LR, 0.611 -LR for Appendicitis Immflamatory Response Score. ROC curve for AIRS was 0.897, higher than Alvarado Score (0.611); being AIRS a more precise diagnostic test than Alvarado Score. CONCLUSIÓN: AIRS showed higher sensitivity (94.7%) and specificity (76.5%) than Alvarado Score (88.5%, 29.6% respectively). Alvarado Score is sensitive enough for acute appendicitis diagnosis, but not specific enough to exclude the diagnosis. AIRS shows a higher Likelihood Ratio and ROC curve than Alvarado Score, but the posttest probability is low for identifying acute appendicitis cases.(au)


Subject(s)
Humans , Male , Female , Adolescent , Adult , Appendectomy , Appendicitis , Abdomen, Acute , Patients
5.
Cancer Metastasis Rev ; 38(4): 553-571, 2019 12.
Article in English | MEDLINE | ID: mdl-31836951

ABSTRACT

Pediatric solid tumors have long been known to shed tumor cells, DNA, RNA, and proteins into the blood. Recent technological advances have allowed for improved capture and analysis of these typically scant circulating materials. Efforts are ongoing to develop "liquid biopsy" assays as minimally invasive tools to address diagnostic, prognostic, and disease monitoring needs in childhood cancer care. Applying these highly sensitive technologies to serial liquid biopsies is expected to advance understanding of tumor biology, heterogeneity, and evolution over the course of therapy, thus opening new avenues for personalized therapy. In this review, we outline the latest technologies available for liquid biopsies and describe the methods, pitfalls, and benefits of the assays that are being developed for children with extracranial solid tumors. We discuss what has been learned in several of the most common pediatric solid tumors including neuroblastoma, sarcoma, Wilms tumor, and hepatoblastoma and highlight promising future directions for the field.


Subject(s)
Liquid Biopsy/methods , Neoplasms/blood , Pediatrics/methods , Child , Humans , Neoplasms/pathology , Randomized Controlled Trials as Topic
6.
Rev. méd. Hosp. José Carrasco Arteaga ; 11(3): 205-214, 30/11/2019. Tablas
Article in Spanish | LILACS | ID: biblio-1103652

ABSTRACT

INTRODUCCIÓN: El protocolo de recuperación rápida (Fast Track o ERAS) en pacientes apendicectomizados por apendicitis complicada, ha mostrado beneficios como: la disminución en la estancia hospitalaria, menor morbilidad y una recuperación postoperatoria rápida brindando al paciente una pronta reinserción laboral y social. MATERIALES Y MÉTODOS: Estudio analítico, participaron 384 pacientes, sometidos a apendicectomía laparoscópica o convencional por apendicitis complicada, se valoró la relación de la aplicabilidad Fast Track con la disminución de la estancia hospitalaria y complicaciones posquirúrgicas, con análisis de las variables estadísticas en el programa SPSS versión 23 y EPIDAT 3.1. RESULTADOS: Prevalencia del sexo femenino con el 51.1%. El 51.6%% se sometieron a cirugía laparoscópica. El uso de antieméticos y opioides postquirúrgicos evitó la náusea posquirúrgica. La deambulación antes de las 12 horas y la ingesta de líquidos evitaron la náusea, vómito y dolor posquirúrgico. La estancia hospitalaria se prolongó más de 4 días en: quienes se usó dren, tuvieron tiempo de cirugía mayor a 91 minutos, presencia de náusea, vómito, dolor, retardo en la aparición de los ruidos hidroaéreos. El reingreso hospitalario se relaciona con antibióticos por más de 4 días, hospitalización por más de 4 días, en cirugía laparoscópica como convencional. CONCLUSIONES: El protocolo Fast Track en apendicitis complicada, se relaciona con: estancia hospitalaria corta, recuperación postoperatoria rápida y menor morbilidad(AU)


BACKGROUND: the fast recovery protocol (Fast Track or ERAS) in patients appendectomized because of complicated appendicitis, has shown benefits such as: hospital stay decrease, lower morbidity and a faster postoperative recovery providing the patient a sooner work and social reintegration. METHODS: analytical study, with 384 participants, undergoing laparoscopic or conventional appendectomy because of complicated appendicitis, we assessed the relationship of the applicability of the postoperative protocol with the reduction of hospital stay and post-surgery complications, using statistical software SPSS version 23 variables and EPIDAT 3.1. RESULTS: prevalence of female patients was 51.1%, 51.6% underwent laparoscopic surgery. The use of antiemetic and postoperative opioids avoided the post-surgical nausea. Early walking and fluid intake avoided nausea, vomiting and post-surgerical pain. Hospital stay lasted more than 4 days for those who used drain, had greater than 91 minutes operating time, presence of post-surgical nausea, vomiting or pain, and delayed appearance of bowel sounds. While hospital re-entry was related to the use of intravenous antibiotics for more than 4 days, hospitalization for more than 4 days in both as conventional laparoscopic surgery. CONCLUSION: Fast Track Protocol for complicated appendicitis is related to a shorter hospital stay, faster postoperative recovery and less postoperative morbidity. (AU)


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Appendicitis/surgery , Peritonitis/surgery , Laparoscopy , Pain/prevention & control , Sex , Methods , Nausea/prevention & control
7.
Rev. méd. Hosp. José Carrasco Arteaga ; 10(2): 155-159, Jul 2018. Imagenes
Article in Spanish | LILACS | ID: biblio-1000322

ABSTRACT

INTRODUCCIÓN: Los tumores neuroendocrinos gástricos son tumores de muy baja prevalencia, constituyendo el aproximadamente 1.8 % de los tumores gástricos. Suelen ser solitarios, con un tamaño entre 4 y 8 cm, con más frecuencia en el sexo masculino con edad promedio de presentación entre 60 - 70 años. Su diagnóstico es cada vez mayor, gracias al uso generalizado de la endoscopia digestiva alta, siendo ésta la prueba de oro. En cuanto a su tratamiento, la resección quirúrgica de los tumores carcinoides gástricos es de elección cuando no se puede optar por resección endoscópica. CASO CLÍNICO: Paciente de 45 años con cuadro clínico de epigastralgia, náusea y diarrea, de dos meses de evolución. Se realiza endoscopía digestiva alta con reporte de úlcera de antro Forrest III. Biopsia: neruroendocrino grado II. Tomografia abdomen: sin datos de actividad en otro sitio fuera de estómago. EVOLUCIÓN: Se realizó gastrectomía subtotal, con reporte negativo en el estudio transoperatorio de líquido de lavado peritoneal. El reporte de patología confirmó el diagnóstico de tumor neuroendócrino GII 3.5 cm unifocal; en estadio III B según las guías clínicas, con vigilancia por un período de un año sin actividad tumoral. CONCLUSIÓN: Al ser el tumor neuroendocrino gástrico un tipo de cáncer poco frecuente, la endoscopía digestiva alta fue fundamental en el diagnóstico de este caso que le llevó al paciente a buscar evaluación médica. Sin embargo, para disminuir el riesgo de su incidencia se recomienda una alimentación rica en frutas, y verduras frescas acompañado de una actividad física adecuada.


BACKGROUND: Gastric neuroendocrine are very low tumors prevalence, constituting approximately 1.8 % of gastric tumors. They are usually solitary, with a size between 4 and 8 cm, most often in the male with average age of presentation between 60 - 70 years. It is diagnosis is increasing, thanks to the widespread use of upper digestive endoscopy, this being the gold standar. Regarding it is treatment; surgical resection of gastric neruroendocrine tumors is one of the choices when endoscopic resection is not possible. CASE REPORT: 45-year-old patient refers epigastralgia, nauseas and diarrhea, since two months ago. Upper digestive endoscopy is performed with report of Forrest III antrum ulcer. Biopsy: grade II neuroendocrine tumor. Abdominal tomography: no activity data in another place outside the stomach. EVOLUTION: Subtotal gastrectomy was performed, with a negative report in the transoperative study of peritoneal lavage fluid. The pathology report confirmed the diagnosis of unifocal neuroendocrine GII 3.5 cm tumor; in stage III B according to clinical guidelines, with surveillance for a period of one year without tumor activity. CONCLUSION: The gastric neuroendocrine is a rare type of cancer; upper gastrointestinal endoscopy was a fundamental in the diagnosis of this case that led the patient to seek medical evaluation. However, to reduce it is incidence is recommended to eat a diet rich in fruits, and fresh vegetables accompanied by adequate physical activity.


Subject(s)
Humans , Male , Stomach Ulcer/etiology , Endoscopy, Gastrointestinal/methods , Carcinoma, Neuroendocrine/diagnosis , Case Management
8.
AIChE J ; 64(12): 4308-4318, 2018 Dec.
Article in English | MEDLINE | ID: mdl-31527922

ABSTRACT

The successful engineering of biosynthetic pathways hinges on understanding the factors that influence acyl carrier protein (ACP) stability and function. The stability and structure of ACPs can be influenced by the presence of divalent cations, but how this relates to primary sequence remains poorly understood. As part of a course-based undergraduate research experience, we investigated the thermostability of type II polyketide synthase (PKS) ACPs. We observed an approximate 40 °C range in the thermostability amongst the 14 ACPs studied, as well as an increase in stability (5 - 26 °C) of the ACPs in the presence of divalent cations. Distribution of charges in the helix II-loop-helix III region was found to impact the enthalpy of denaturation. Taken together, our results reveal clues as to how the sequence of type II PKS ACPs relates to their structural stability, information that can be used to study how ACP sequence relates to function.

9.
Pflugers Arch ; 450(4): 255-61, 2005 Jul.
Article in English | MEDLINE | ID: mdl-15909181

ABSTRACT

K+ depletion exerts dramatically variable effects on different potassium channels. Here we report that Shab channels are rather stable in the absence of either internal or external K+ alone; however, its stability is greater with K+ outside the cell. In contrast, with 0 K+ (non-added) solutions on both sides of the membrane, the conductance (G(K)) is rapidly and irreversibly lost. G(K) is lost with the channels closed and regardless of the composition of the 0 K+ solutions. In comparison, it is known that the Shaker B G(K) collapses only if the channels are gated in 0 K+, Na+-containing solutions. In order to compare the behavior of Shab to that of Shaker, we show that after extensively gating the channels in 0 K+ N-methyl-D-glucamine solutions, most Shaker channels remain stable, and in a conformation where G(K) collapses as soon as there is Na+ in the solutions. Regarding ion conduction, in contrast to Kv2.1 and Shaker A463C that have a sizable G(Na) in 0 K+, Shab, which shares a 463-cysteine and an identical signature sequence with these channels, does not appreciably conduct Na+, although it presents a significant Cs+ conductance. The observations suggest that there are at least two sites where K+ binds and thus maintains Shab G(K) stable, one internal and the other(s) most likely located outside the selectivity filter.


Subject(s)
Potassium/physiology , Animals , Cells, Cultured , Electric Conductivity , Patch-Clamp Techniques , Spodoptera
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