Reversal of high-glucose-induced transcriptional and epigenetic memories through NRF2 pathway activation.

Diabetes complications such as nephropathy, retinopathy, or cardiovascular disease arise from vascular dysfunction. In this context, it has been observed that past hyperglycemic events can induce long-lasting alterations, a phenomenon termed "metabolic memory." In this study, we evaluated the genome-wide gene expression and chromatin accessibility alterations caused by transient high-glucose exposure in human endothelial cells (ECs) in vitro. We found that cells exposed to high glucose exhibited substantial gene expression changes in pathways known to be impaired in diabetes, many of which persist after glucose normalization. Chromatin accessibility analysis also revealed that transient hyperglycemia induces persistent alterations, mainly in non-promoter regions identified as enhancers with neighboring genes showing lasting alterations. Notably, activation of the NRF2 pathway through NRF2 overexpression or supplementation with the plant-derived compound sulforaphane, effectively reverses the glucose-induced transcriptional and chromatin accessibility memories in ECs. These findings underscore the enduring impact of transient hyperglycemia on ECs' transcriptomic and chromatin accessibility profiles, emphasizing the potential utility of pharmacological NRF2 pathway activation in mitigating and reversing the high-glucose-induced transcriptional and epigenetic alterations.

IWATE criteria are associated with perioperative outcomes in robotic hepatectomy: a retrospective review of 225 resections.

BACKGROUND: Robotic hepatectomy (RH) is increasingly utilized for minor and major liver resections. The IWATE criteria were developed to classify minimally invasive liver resections by difficulty. The objective of this study was to apply the IWATE criteria in RH and to describe perioperative and oncologic outcomes of RH over the last decade at our institution. METHODS: Perioperative and oncologic outcomes of patients who underwent RH between 2011 and 2019 were retrospectively collected. The difficulty level of each operation was assessed using the IWATE criteria, and outcomes were compared at each level. Univariate linear regression was performed to characterize the relationship between IWATE criteria and perioperative outcomes (OR time, EBL, and LOS), and a multivariable model was also developed to address potential confounding by patient characteristics (age, sex, BMI, prior abdominal surgery, ASA class, and simultaneous non-hepatectomy operation). RESULTS: Two hundred and twenty-five RH were performed. Median IWATE criteria for RH were 6 (IQR 5-9), with low, intermediate, advanced, and expert resections accounting for 23% (n = 51), 34% (n = 77), 32% (n = 72), and 11% (n = 25) of resections, respectively. The majority of resections were parenchymal-sparing approaches, including anatomic segmentectomies and non-anatomic partial resections. 30-day complication rate was 14%, conversion to open surgery occurred in 9 patients (4%), and there were no deaths within 30 days postoperatively. In the univariate linear regression analysis, IWATE criteria were positively associated with OR time, EBL, and LOS. In the multivariable model, IWATE criteria were independently associated with greater OR time, EBL, and LOS. Two-year overall survival for hepatocellular carcinoma and intrahepatic cholangiocarcinoma was 94% and 50%, respectively. CONCLUSION: In conclusion, the IWATE criteria are associated with surgical outcomes after RH. This series highlights the utility of RH for difficult hepatic resections, particularly parenchymal-sparing resections in the posterosuperior sector, extending the indication of minimally invasive hepatectomy in experienced hands and potentially offering select patients an alternative to open hepatectomy or other less definitive liver-directed treatment options.

Food Insecurity in a Pediatric Emergency Department and the Feasibility of Universal Screening.

INTRODUCTION: Children with food insecurity (FI) experience adverse health outcomes due to inadequate quantity or quality of food. Food insecurity may be high among families seeking emergency care. The Hunger Vital Sign (HVS) is a two-question validated tool used to screen families for FI. Our goal in this study was to assess prevalence of FI among emergency department (ED) patients, patient-level risk factors for FI, and the feasibility of screening. METHODS: This was a cross-sectional analysis of FI in the ED. Parents or guardians of ED patients and adult patients (18 years or older) were approached for screening using the HVS during screening periods spanning weekdays/weekends and days/evenings. All ED patients were eligible, excluding siblings, repeat visits, critically ill patients, minors without a guardian, and families that healthcare staff asked us not to disturb. Families answered the HVS questions verbally or in writing, based on preference. Families with positive screens received information about food resources. We summarized patient and visit characteristics and defined medical complexity using a published algorithm. Multivariable logistic regression was used to assess FI risk factors. RESULTS: In July-August 2019, 527 patients presented during screening periods: 439 agreed to screening, 18 declined, 19 met exclusions, and 51 were missed. On average the screening tool required five minutes (range 3-10 minutes) to complete. Most families (328; 75%) preferred to answer in writing rather than verbally. Overall, 77 participants (17.5%) screened positive for FI. In regression analyses, FI was associated with self-reported race/ethnicity (combined variable) of African American or Black (odds ratio [OR] 5.21, 95% confidence interval [CI], 2.13-12.77), Hispanic (OR 3.47, 95% CI, 1.48-8.15), or mixed/other (OR 3.81, 95% CI, 1.54-9.39), compared to non-Hispanic white. FI was also associated with public insurance type (OR 5.74, 95% CI, 2.52-13.07, reference: private insurance), and each year of increasing patient age (OR 1.05, 95% CI, 1.01-1.09). There were no associations between FI and medical complexity or preferred language. CONCLUSION: Food insecurity was common among our ED patients. Race and ethnicity, insurance status, and increasing patient age were associated with increased odds of FI. Efforts to include universal FI screening for ED patients with immediate connection to resources will enhance overall care quality and address important health needs.

Perioperative protocol to reduce blood transfusions in total knee o hip replacement patients / [Implementación de protocolo perioperatorio para disminuir tasa de transfusiones en pacientes sometidos a reemplazo total de cadera o rodilla primarios]

Introduction: Patient Blood Management (PBM) programs improve patient care and reduce health costs. It includes detection of presurgical anemia, reduction of blood loss and improvement of patient-specific anemic reserve. The aim of this study is to assess the effect of a PBM program on transfusion rate, length of stay (LOS) and adverse events. Methods: We developed a retrospective observational study. We included patients who underwent total hip (THR) o knee replacement (TKR). Our PBM involved preoperative assessment, administration of 2 doses of tranexamic acid, application of restrictive transfusion criteria and use of IV iron. We compared results between the group of patients before and the one after the PBM implementation. Results: We included 179 patients (80 TKR and 99 THR) who underwent surgery before PBM implementation from January to December 2014 (Group A), and 187 patients (103 TKR and 84 THR) who underwent arthroplasty after PBM application from January to November 2016 (Group B). In Group A, hemoglobin drop was larger than in Group B, for TKR (5.1±1.2 vs. 4.2±1.2 g/dl; p<0,05) and for THR (4.7±1.3 vs. 3.8±1.3 g/dl; p<0,05). In group A, more patients were transfused (31.8% vs. 2.7%; p<0.001). LOS was longer for patients in group A, in both surgeries (for TKA, 3.98±1.4days vs. 2.99±0.95 days; p<0.0001; for THA 3.68±1.06days vs. 2.88±0.75days; p<0.0001). No significant differences were found regarding adverse events. Conclusion: Our PBM program saved transfusions after primary TKR and THR and lowered LOS, without risking patients to higher number of complications or death.

Introducción: Los protocolos de manejo de anemia perioperatoria mejoran el cuidado del paciente y disminuyen los costos en salud. El objetivo de este estudio fue identificar el efecto de dicho programa en pacientes sometidos a reemplazo total de cadera (RTC) o rodilla (RTR), en la tasa de transfusiones, tiempo de estadía hospitalaria y eventos adversos. Métodos: Se realizó un estudio observacional retrospectivo, incluyendo pacientes sometidos a RTC o RTR primarios. El programa abarcó la valoración preoperatoria, el uso de 2 dosis de ácido tranexámico, la aplicación de transfusiones restringidas, y el uso de hierro suplementario. Se compararon los resultados entre pacientes pre y post implementación del protocolo. Resultados: Se incluyeron 179 pacientes (80 RTR y 99 RTC) pre protocolo entre enero y diciembre 2014 (grupo A) y 187 casos (103 RTR y 84 RTC) post protocolo entre enero y noviembre 2016 (grupo B). En el grupo A, la caida de hemoglobina fue mayor que en el grupo B en RTR (5,1±1,2 vs. 4,2±1,2 g/dl; p<0,05) y en RTC (4,7±1.3 vs. 3,8±1.3 g/dl; p<0,05). Hubo mayor requerimiento transfusional en el grupo A (31,8% vs. 2,7%; p<0,001). El tiempo de estadía hospitalaria (TEH) fue mayor en el grupo A para ambas cirugías (en RTR 3,98±1,4días vs. 2,99±0,95 días; p<0,0001; en RTC 3,68±1,06días vs. 2,88±0,75días; p<0,0001). No se encontraron diferencias significativas respecto a eventos adversos. Conclusión: En ambas artroplastias, nuestro programa disminuyó la cantidad de transfusiones, la caída de hemoglobina y la estadía hospitalaria, sin aumentar el número de complicaciones.

Prevalence of Health Care and Hospital Worker SARS-CoV-2 IgG Antibody in a Pediatric Hospital.

OBJECTIVES: Asymptomatic transmission of coronavirus disease 2019 (COVID-19) in health care settings is not well understood. In this study, we aimed to determine the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) antibodies in health care and hospital workers (HCHWs) and assess how antibody levels change over time. METHODS: Cross-sectional study of employed HCHWs at a freestanding, urban pediatric tertiary care hospital. Employed HCHWs ≥18 years old who were asymptomatic and worked in clinical hospital locations were eligible to participate. Participants completed blood draws and surveys at baseline (between May 4, 2020, and June 2, 2020) and 2 months later (between July 6, 2020, and August 7, 2020). Surveys collected demographic information, SARS-CoV-2 exposures, and previous COVID-19 diagnosis. RESULTS: In total, 530 participants enrolled in and completed baseline study activities. The median age was 37 years (range 19-67 years); 86% identified as female, and 80% identified as white. Two months later, 481 (91%) HCHWs completed another survey and blood draw. Four of 5 (0.9%) seropositive subjects at baseline remained seropositive at 2 months, although 3 had decreasing IgG indices. Five (1.0%) seropositive individuals, including 4 who were previously seropositive and 1 newly seropositive, were detected 2 months later. History of positive SARS-CoV-2 polymerase chain reaction testing results (P < .001) and history of COVID-19 exposure (P < .001) were associated with presence of SARS-CoV-2 antibodies. CONCLUSIONS: SARS-CoV-2 antibodies were detected in 1% of HCHWs in an urban pediatric hospital in a city with moderate SARS-CoV-2 prevalence. Participants with a known previous COVID-19 diagnosis showed a decline or loss of IgG antibodies over 2 months. These results have implications for identifying those with previous exposure and for ongoing public health recommendations for ensuring workplace safety.

In Kluyveromyces lactis a Pair of Paralogous Isozymes Catalyze the First Committed Step of Leucine Biosynthesis in Either the Mitochondria or the Cytosol.

Divergence of paralogous pairs, resulting from gene duplication, plays an important role in the evolution of specialized or novel gene functions. Analysis of selected duplicated pairs has elucidated some of the mechanisms underlying the functional diversification of Saccharomyces cerevisiae (S. cerevisiae) paralogous genes. Similar studies of the orthologous pairs extant in pre-whole genome duplication yeast species, such as Kluyveromyces lactis (K. lactis) remain to be addressed. The genome of K. lactis, an aerobic yeast, includes gene pairs generated by sporadic duplications. The genome of this organism comprises the KlLEU4 and KlLEU4BIS paralogous pair, annotated as putative α-isopropylmalate synthases (α-IPMSs), considered to be the orthologs of the S. cerevisiae ScLEU4/ScLEU9 paralogous genes. The enzymes encoded by the latter two genes are mitochondrially located, differing in their sensitivity to leucine allosteric inhibition resulting in ScLeu4-ScLeu4 and ScLeu4-ScLeu9 sensitive dimers and ScLeu9-ScLeu9 relatively resistant homodimers. Previous work has shown that, in a Scleu4Δ mutant, ScLEU9 expression is increased and assembly of ScLeu9-ScLeu9 leucine resistant homodimers results in loss of feedback regulation of leucine biosynthesis, leading to leucine accumulation and decreased growth rate. Here we report that: (i) K. lactis harbors a sporadic gene duplication, comprising the KlLEU4, syntenic with S. cerevisiae ScLEU4 and ScLEU9, and the non-syntenic KlLEU4BIS, arising from a pre-WGD event. (ii) That both, KlLEU4 and KlLEU4BIS encode leucine sensitive α-IPMSs isozymes, located in the mitochondria (KlLeu4) and the cytosol (KlLeu4BIS), respectively. (iii) That both, KlLEU4 or KlLEU4BIS complement the Scleu4Δ Scleu9Δ leucine auxotrophic phenotype and revert the enhanced ScLEU9 transcription observed in a Scleu4Δ ScLEU9 mutant. The Scleu4Δ ScLEU9 growth mutant phenotype is only fully complemented when transformed with the syntenic KlLEU4 mitochondrial isoform. KlLEU4 and KlLEU4BIS underwent a different diversification pathways than that leading to ScLEU4/ScLEU9. KlLEU4 could be considered as the functional ortholog of ScLEU4, since its encoded isozyme can complement both the Scleu4Δ Scleu9Δ leucine auxotrophy and the Scleu4Δ ScLEU9 complex phenotype.

[Preferences and limitations of hematologists to address the complexity of myelodysplastic syndromes]. / Preferencias y limitaciones de los hematólogos para afrontar la complejidad de los síndromes mielodisplásicos.

Argentina is a country characterized by a heterogeneous distribution of its population, its economic resources and, consequently, access to health services, which could affect the diagnosis and treatment of patients with myelodysplastic syndromes. Based on the increasing complexity to arrive at the diagnosis, estimate the risk and indicate an adequate treatment, we have conducted a survey of twenty-three questions to evaluate patterns of clinical practice. The questionnaire was distributed among 850 hematologists registered at the XXII Argentine Congress of Hematology, and 195 (22.9%) were answered; 40.0% report that < 75% of their patients access the karyotype, bone marrow histology and flow cytometry. This access decreases significantly due to low health coverage (OR 6.3), in the adult population (OR 3.8), when the cytogenetic study is derived (OR 3.2) and outside the metropolitan area of Buenos Aires (OR 2.4). The respondents avoid oncological terminologies (77.0%) when introducing the diagnosis and use the international prediction system or its review (74.2%) to stage risk. However, they prioritize age when selecting treatment and pediatricians preferentially recommend the transplantation of hematopoietic precursors. Most of the haematologists have prescribed the recommended treatments, whose suspensions were related to lack of response (62.7%), with reduced participation in clinical trials (8.9%). Therefore, they report heterogeneity in the access to complementary diagnostic tools with differences at the time of indicating a treatment, depending on the age of their patients without apparent limitations in their prescription.

La Argentina es un país caracterizado por una distribución heterogénea de su población, de sus recursos económicos y, consiguientemente, del acceso a los servicios de salud, lo cual podría afectar el diagnóstico y tratamiento de los pacientes con síndromes mielodisplásicos. Basados en la complejidad creciente para arribar al diagnóstico, estimar el riesgo e indicar un tratamiento adecuado, hemos conducido una encuesta de veintitrés preguntas para evaluar patrones de práctica clínica. El cuestionario se distribuyó entre los 850 hematólogos argentinos inscriptos al XXII Congreso Argentino de Hematología y 195 (22.9%) fueron contestados. El 40.0% refieren que < 75% de sus pacientes acceden al cariotipo, histología de la médula ósea y citometría de flujo. Este acceso disminuye significativamente por una baja cobertura sanitaria (OR 6.3), en población adulta (OR 3.8), al derivar el estudio citogenético (OR 3.2) y fuera del área metropolitana de Buenos Aires (OR 2.4). Los encuestados evitan terminologías oncológicas (77.0%) al introducir el diagnóstico y utilizan el sistema internacional de predicción o su revisión (74.2%) para estadificar riesgo. Sin embargo, éstos priorizan la edad al seleccionar tratamiento y los pediatras indican preferentemente el trasplante de precursores hematopoyéticos. La mayoría de los hematólogos ha prescripto los tratamientos recomendados, cuyas suspensiones se relacionaron con falta de respuesta (62.7%), con participación reducida en ensayos clínicos (8.9%). Por ende, refieren heterogeneidad en el acceso a las herramientas diagnósticas complementarias con diferencias al momento de indicar un tratamiento, dependiendo de la edad de sus pacientes, sin limitaciones aparentes en su prescripción.

Preferencias y limitaciones de los hematólogos para afrontar la complejidad de los síndromes mielodisplásicos / Preferences and limitations of hematologists to address the complexity of myelodysplastic syndromes

La Argentina es un país caracterizado por una distribución heterogénea de su población, de sus recursos económicos y, consiguientemente, del acceso a los servicios de salud, lo cual podría afectar el diagnóstico y tratamiento de los pacientes con síndromes mielodisplásicos. Basados en la complejidad creciente para arribar al diagnóstico, estimar el riesgo e indicar un tratamiento adecuado, hemos conducido una encuesta de veintitrés preguntas para evaluar patrones de práctica clínica. El cuestionario se distribuyó entre los 850 hematólogos argentinos inscriptos al XXII Congreso Argentino de Hematología y 195 (22.9%) fueron contestados. El 40.0% refieren que < 75% de sus pacientes acceden al cariotipo, histología de la médula ósea y citometría de flujo. Este acceso disminuye significativamente por una baja cobertura sanitaria (OR 6.3), en población adulta (OR 3.8), al derivar el estudio citogenético (OR 3.2) y fuera del área metropolitana de Buenos Aires (OR 2.4). Los encuestados evitan terminologías oncológicas (77.0%) al introducir el diagnóstico y utilizan el sistema internacional de predicción o su revisión (74.2%) para estadificar riesgo. Sin embargo, éstos priorizan la edad al seleccionar tratamiento y los pediatras indican preferentemente el trasplante de precursores hematopoyéticos. La mayoría de los hematólogos ha prescripto los tratamientos recomendados, cuyas suspensiones se relacionaron con falta de respuesta (62.7%), con participación reducida en ensayos clínicos (8.9%). Por ende, refieren heterogeneidad en el acceso a las herramientas diagnósticas complementarias con diferencias al momento de indicar un tratamiento, dependiendo de la edad de sus pacientes, sin limitaciones aparentes en su prescripción.

Argentina is a country characterized by a heterogeneous distribution of its population, its economic resources and, consequently, access to health services, which could affect the diagnosis and treatment of patients with myelodysplastic syndromes. Based on the increasing complexity to arrive at the diagnosis, estimate the risk and indicate an adequate treatment, we have conducted a survey of twenty-three questions to evaluate patterns of clinical practice. The questionnaire was distributed among 850 hematologists registered at the XXII Argentine Congress of Hematology, and 195 (22.9%) were answered; 40.0% report that < 75% of their patients access the karyotype, bone marrow histology and flow cytometry. This access decreases significantly due to low health coverage (OR 6.3), in the adult population (OR 3.8), when the cytogenetic study is derived (OR 3.2) and outside the metropolitan area of Buenos Aires (OR 2.4). The respondents avoid oncological terminologies (77.0%) when introducing the diagnosis and use the international prediction system or its review (74.2%) to stage risk. However, they prioritize age when selecting treatment and pediatricians preferentially recommend the transplantation of hematopoietic precursors. Most of the haematologists have prescribed the recommended treatments, whose suspensions were related to lack of response (62.7%), with reduced participation in clinical trials (8.9%). Therefore, they report heterogeneity in the access to complementary diagnostic tools with differences at the time of indicating a treatment, depending on the age of their patients without apparent limitations in their prescription.

Flow cytometry "Ogata score" for the diagnosis of myelodysplastic syndromes in a real-life setting. A Latin American experience.

INTRODUCTION: Flow cytometry (FC) is a helpful tool for the diagnosis of myelodysplastic syndrome (MDS). Different FC score systems have been developed. The "Ogata score" is a simple diagnostic score that has been validated having a sensitivity of 69% and a specificity of 92% in low-risk MDS. We aimed to study the feasibility and the utility of the "Ogata score" for the diagnosis of MDS among Latin America (LA) Laboratories. METHODS: This is a case and control study conducted in LA institutions members of Grupo Latinoamericano de Mielodisplasia (GLAM). A total of 146 MDS patients and 57 control patients were included. "Ogata score" was calculated. RESULTS: The sensitivity of "Ogata score" was 75.6% (95% CI, 66.8-81.3), specificity was 91.2% (95% CI, 79.7-96.7), PPV was 95.6% (95% CI, 88.5-98.3), and NPV was 65.4% (95% CI, 49.1-71.9). In low/intermediate-1 IPSS patients group, the sensitivity was 70.1% (95% CI, 60.2-78.2), specificity was 91.2% (CI-95%, 79.7-96.7), PPV was 94.2% (95% CI, 86.4-97.8), and NPV was 62.1% (95% CI, 53.0-78.7). In the group of patients "without MDS specific markers" (patients without ring sideroblasts, blast excess, or chromosomal abnormalities), the sensitivity was 66.7% (CI-95%, 55.8-76.0), specificity was 91.2% (95% CI, 79.7-96.7), PPV was 92.3% (95% CI, 82.2-97.1), and NPV was 63.5% (95% CI, 51.9-73.5). CONCLUSIONS: The diagnostic power found in this study was similar to the reported by Della-Porta et al. Also in LA, the analysis was made in modern equipment with acquisition of at least 100 000 events which permits a good reproducibility of the results.

Factores psicosociales laborales y el síndrome de burnout en docentes de enseñanza media básica (secundaria) de la zona metropolitana de Guadalajara, México / Psychosocial occupational factors and burnout syndrome among secondary school teachers from the metropolitan zone of Guadalajara, México

Este estudio busca identificar la relación entre los factores psicosociales laborales y el Síndrome de burnout en los docentes del nivel medio básico del sistema educativo oficial, de la Zona Metropolitana de Guadalajara, Jalisco, México.Se realizó un estudio cuantitativo: descriptivo, transversal y observacional, en una muestra representativa de 360 maestros que laboraban frente a grupo, de una población de 8,935. Para la selección de los docentes se realizó un muestreo por conglomerados, seleccionando aleatoreamente29 escuelas y de ellas a 13 docentes.Para la captación de datos se utilizaron 3 instrumentos autoaplicados: Encuesta de datos generales y laborales, escala de Maslach Burnout Inventory (M.B.I:), Batería de Factores Psicosociales en el Trabajo Académico (FPSIS ACADEMICO).Para el análisis y proceso de datos se utilizó el paquete estadístico Epi.Info 6.Se encontró que el 80 por ciento de los docentes tenía alguna dimensión de la escala de Maslasch “quemada”. Se identificó un 43.7 por ciento con agotamiento emocional, un 40.3 por ciento en baja realización personal, y un 13.3 por ciento, con despersonalización. Los maestros identifican la presencia de factores de naturaleza psicosocial en los espacios laborales educativos, en las siete sub escalas que se evaluaron y como factor de riesgo para presentar agotamiento emocional, encontrando nivelesaltos con mayor frecuencia en: exigencias laborales 40.9 per cent y remuneración del rendimiento 29.5 per cent. Se concluye que la presencia de factores psicosociales laborales negativos en los espacios laborales afecta significativamente a los docentes, ocasionando un mayor riesgo de presentar agotamiento emocional.

The present study aims at identifying the link between psychosocial occupational factors and the burnout Syndrome among high school teachers from the mainstream educative system at the Metropolitan Zone of Guadalajara, Jalisco, México.A quantitative descriptive, cross-sectional and observational study was carried out on a representative sample of 360 teachers who worked in front of a group, selected from a total population of 8,935. Cluster sampling was used for teacher selection: 29 schools were randomly selected and from these, 13 teachers were chosen.Data collection used 3 self-applied instruments: a general and labor data survey, the Maslach Burnout Inventory (M.B.I) Scale, and a Psychosocial Factors in Academic Work assessment battery (ACADEMIC FPSIS).The Epi.Info 6 statistic pack was used or data process and analysis.The results showed that 80 percent of teachers had some dimension of the Maslach scale “burntout”. Emotional exhaustion was identified among 43.7 percent, low personal accomplishment was observed in 40.3 percent, and depersonalization in 13.3 percent. Teachers evidenced the presence of psychosocial factors in the fields of educative work in the seven subscales that were evaluated, and as a risk factor for emotional exhaustion. High levels were most commonly observed among occupational demands (40.9 percent) and performance compensation 29.5 percent.To conclude, the presence of negative labor psychosocial factors in occupational fields has a significant impact on teachers, resulting in a higher risk for emotional exhaustion.