Ketogenic diet modifies ribosomal protein dysregulation in KMT2D Kabuki syndrome.

BACKGROUND: Kabuki syndrome (KS) is a genetic disorder caused by DNA mutations in KMT2D, a lysine methyltransferase that methylates histones and other proteins, and therefore modifies chromatin structure and subsequent gene expression. Ketones, derived from the ketogenic diet, are histone deacetylase inhibitors that can 'open' chromatin and encourage gene expression. Preclinical studies have shown that the ketogenic diet rescues hippocampal memory neurogenesis in mice with KS via the epigenetic effects of ketones. METHODS: Single-cell RNA sequencing and mass spectrometry-based proteomics were used to explore molecular mechanisms of disease in individuals with KS (n = 4) versus controls (n = 4). FINDINGS: Pathway enrichment analysis indicated that loss of function mutations in KMT2D are associated with ribosomal protein dysregulation at an RNA and protein level in individuals with KS (FDR <0.05). Cellular proteomics also identified immune dysregulation and increased abundance of other lysine modification and histone binding proteins, representing a potential compensatory mechanism. A 12-year-old boy with KS, suffering from recurrent episodes of cognitive decline, exhibited improved cognitive function and neuropsychological assessment performance after 12 months on the ketogenic diet, with concomitant improvement in transcriptomic ribosomal protein dysregulation. INTERPRETATION: Our data reveals that lysine methyltransferase deficiency is associated with ribosomal protein dysfunction, with secondary immune dysregulation. Diet and the production of bioactive molecules such as ketone bodies serve as a significant environmental factor that can induce epigenetic changes and improve clinical outcomes. Integrating transcriptomic, proteomic, and clinical data can define mechanisms of disease and treatment effects in individuals with neurodevelopmental disorders. FUNDING: This study was supported by the Dale NHMRC Investigator Grant (APP1193648) (R.D), Petre Foundation (R.D), and The Sydney Children's Hospital Foundation/Kids Research Early and Mid-Career Researcher Grant (E.T).

Development, validation and implementation of a program to detect malnutrition with NRS-2002 screening tool in patients, between 16 and 93 years, from the oncology and hematology service from Valencia during 2017 and 2018 / Desarrollo, validación e implementación de un programa de detección de desnutrición con herramienta de cribado NRS-2002 en pacientes del servicio de oncología y hematología

INTRODUCTION: Hospital malnutrition (HM) is an increasingly prevalent situation, which involves both an increase in health costs, and also a decrease in the life quality and greater morbimortality. Nutritional screening is essential to detect malnutrition early and avoid these complications. OBJECTIVES: To develop, validate and implement the Nutritional Risk Screening 2002 (NRS-2002) tool at the admission and during the hospitalization of a patient in the oncohematology service in a third level hospital, and know their nutritional status at the admission and the discharge. METHODS: NRS-2002 was performed on all patients admitted to the oncohaematology service, followed by the complete nutritional assessment (NA) to check its validity. NRS-2002 is repeated weekly to determine the degree of malnutrition during the hospital stay. RESULTS: 573 patients were admitted to the oncohematology service, of which a 34.4% suffered from malnutrition, 44.7% had risk of malnutrition and 20.9% were in good nutritional condition, at the time they were admitted to hospital according to the NRS-2002. In patients admitted for more than a week, NRS-2002 was performed weekly and found that, upon discharge, a 34.4% were malnourished, 50.8% had a risk of malnutrition and the last 14.76% were in good nutritional status; also a 12.3% worsened their nutritional status, the 68.9% maintained it and only a 18.9% improved it. 78.8% of patients with longer admissions require a NA. DISCUSSION: Due to the high risk of malnutrition in hospital admission, the use of nutritional screening is necessary, both at admission and during hospital stay to avoid nutritional deterioration during the same. CONCLUSIONS: Our results suggest that the NRS-2002 is a simple and effective method for early malnutrition detection

INTRODUCCIÓN: La desnutrición hospitalaria es una situación cada vez más prevalente, que implica un aumento de los costos de salud, una disminución de la calidad de vida y una mayor morbimortalidad. El cribado nutricional es fundamental para detectar precozmente la desnutrición y evitar complicaciones. OBJETIVOS: Desarrollar, validar e implementar la herramienta Nutritional Risk Screening 2002 (NRS-2002) al ingreso y durante la hospitalización de un paciente en el servicio de oncohematología de un hospital de tercer nivel, y conocer su estado nutricional al ingreso y al alta. MÉTODOS: se realizó la NRS-2002 a todos los pacientes ingresados ​​en el servicio de oncohematología, seguida de la valoración nutricional completa (VN) para comprobar su validez. Para medir la concordancia entre los dos diagnósticos, se calculó el Kappa de Cohen para cada visita. El nivel de asociación entre las variables se midió mediante la medida de Goodman y Kruskal. RESULTADOS: 573 pacientes ingresaron en el servicio de oncohematología, de los cuales: 34,4% desnutrición, 44,7% riesgo de desnutrición y 20,9% buen estado nutricional, al ingreso hospitalario según ENN-2002. En los pacientes ingresados ​​por más de una semana, se realizó NRS-2002 semanalmente y se encontró que al alta presentaban: 34,4% de desnutrición, 50,8% de riesgo de desnutrición y 14,76% de buen estado nutricional; además el 12,3% empeora su estado nutricional, el 68,9% lo mantiene y solo el 18,9% lo mejora. El 78,8% de los pacientes con ingresos más prolongados requieren una NV. CONCLUSIONES: Nuestros resultados sugieren que el NRS-2002 es un método simple y efectivo para la detección temprana de desnutrición. Es importante un seguimiento nutricional durante el período de hospitalización, ya que los pacientes son susceptibles de empeoramiento de su estado nutricional

Estado Nutricional e indicadores de qualidade em terapia nutricional de pacientes hematológicos internados em Hospital Público Universitário do Brasil / Nutritional status ans quality indicators in nutritional therapy of hematological patients hospitalized in Public University Hospital of Brazil

Objetivo: Avaliar o estado nutricional e a prevalência de adequação dos indicadores de qualidade em terapia nutricional (IQTNs) de pacientes hospitalizados na unidade de hematologia. Métodos: Estudo de caráter transversal, retrospectivo e descritivo, realizado no período fevereiro a maio de 2017, no qual foi avaliado o estado nutricional e os IQTNs (1- realização de triagem nutricional até 48 horas de internação, 2- medida de Índice de Massa Corporal (IMC), 3- catabolismo proteico pela circunferência do braço) de 133 pacientes internados na unidade de hematologia do Hospital Universitário da rede pública de saúde em Fortaleza, por meio de informações contidas no banco de dados dos serviços de nutrição. Resultados: A amostra predominante era do sexo feminino (60,9%). A idade média geral foi em torno de 45±16,0 anos. Observou-se que a maioria dos pacientes avaliados foram classificados como eutróficos pelo IMC (41,6%) e circunferência do braço (43,6%); no entanto, de acordo com a triagem nutricional, a maioria dos pacientes internados encontrava- se em risco nutricional (55,3%). Com relação aos IQTNs, observou-se conformidade no indicador 1 e não conformidade nos indicadores 2 e 3. Conclusão: Conclui-se que a maioria dos pacientes eram eutróficos; no entanto, apresentavam risco nutricional. Além disso, O IMC foi o único indicador de qualidade que atingiu a meta proposta. Sendo assim, ressalta-se a importância da avaliação periódica dos outros IQTNs do serviço de nutrição, visto que os pacientes hematológicos merecem atenção especial por apresentarem elevado risco nutricional e necessitarem de cuidados rigorosos

Objective: To evaluate the nutritional status and the adequacy prevalence of quality indicators for nutrition therapy (QINTs) of hospitalized patients in the hematology unit. Methods: A cross-sectional, retrospective and descriptive study was carried out between February and May 2017, in which nutritional status and QINTs were evaluated (1- nutritional screening up to 48 hours of hospitalization, 2- body mass index (BMI), 3- protein catabolism by arm circumference) of 133 patients hospitalized at the University Hospital of the public health service in Fortaleza, through information contained in the database of the nutrition services. Results: The predominant sample was female (60.9%). Overall mean age was around 45 ± 16.0 years. It was observed that the majority of the evaluated patients were classified as eutrophic based on BMI (41.6%) and arm circumference (43.6%); however, according to nutritional screening, most hospitalized patients were at nutritional risk (55.3%). With regard to QINTs, compliance with indicator 1 and nonconformity in indicators 2 and 3 were observed. Conclusions: It is concluded that the majority of patients were eutrophic; however, presented nutritional risk. The BMI was the only quality indicator that met the proposed goal. Therefore, the importance of periodic evaluation of other indicators of quality of nutrition service is emphasized, since hematological patients deserve special attention because they present high nutritional risk and require rigorous care

Objetivo: Evaluar el estado nutricional y la prevalencia de adecuación de los indicadores de calidad en terapia nutricional (IQTNs) de pacientes hospitalizados en la unidad de hematología. Método: El estudio de carácter transversal, retrospectivo y descriptivo, realizado en el período febrero a mayo de 2017, en el cual se evaluó el estado nutricional y los IQTNs (1- realización de clasificación nutricional hasta 48 horas de internación, 2- medida de Índice de Masa Corporal (IMC), 3- catabolismo proteico por la circunferencia del brazo) de 133 pacientes internados en la unidad de hematología del Hospital Universitario de la red pública de salud en Fortaleza, por medio de informaciones contenidas en el banco de datos de los servicios de nutrición. Resultados: La muestra predominante era del sexo femenino (60,9%). La edad media general fue de alrededor de 45 ± 16,0 años. Se observó que la mayoría de los pacientes evaluados fueron clasificados como eutróficos por el IMC (41,6%) y circunferencia del brazo (43,6%); sin embargo, de acuerdo con la clasificación nutricional, la mayoría de los pacientes internados se encontraba en riesgo nutricional (55,3%). Con respecto a los IQTNs, se observó conformidad en el indicador 1 y no conformidad en los indicadores 2 y 3. Conclusiones: Se concluye que la mayoría de los pacientes eran eutróficos; sin embargo, presentaban riesgo nutricional. Además, el IMC fue el único indicador de calidad que alcanzó la meta propuesta. Por lo tanto, se resalta la importancia de la evaluación periódica de los otros IQTNs del servicio de nutrición, ya que los pacientes hematológicos merecen atención especial por presentar un alto riesgo nutricional y necesitan cuidados rigurosos

A ketogenic diet rescues hippocampal memory defects in a mouse model of Kabuki syndrome.

Kabuki syndrome is a Mendelian intellectual disability syndrome caused by mutations in either of two genes (KMT2D and KDM6A) involved in chromatin accessibility. We previously showed that an agent that promotes chromatin opening, the histone deacetylase inhibitor (HDACi) AR-42, ameliorates the deficiency of adult neurogenesis in the granule cell layer of the dentate gyrus and rescues hippocampal memory defects in a mouse model of Kabuki syndrome (Kmt2d+/ßGeo). Unlike a drug, a dietary intervention could be quickly transitioned to the clinic. Therefore, we have explored whether treatment with a ketogenic diet could lead to a similar rescue through increased amounts of beta-hydroxybutyrate, an endogenous HDACi. Here, we report that a ketogenic diet in Kmt2d+/ßGeo mice modulates H3ac and H3K4me3 in the granule cell layer, with concomitant rescue of both the neurogenesis defect and hippocampal memory abnormalities seen in Kmt2d+/ßGeo mice; similar effects on neurogenesis were observed on exogenous administration of beta-hydroxybutyrate. These data suggest that dietary modulation of epigenetic modifications through elevation of beta-hydroxybutyrate may provide a feasible strategy to treat the intellectual disability seen in Kabuki syndrome and related disorders.

A short nutritional intervention in a cohort of hematological inpatients improves energy and protein intake and stabilizes nutritional status.

INTRODUCTION: Oncohematological diseases are associated with an important prevalence of malnutrition. AIM: Our aim is to determine if early recognition and treatment of malnourished hematological inpatients can improve their oral intake, nutritional status and reduce the length of hospital stay. METHODS: Prospective 2-year study conducted in a cohort of hematology inpatients. Malnutrition Screening Tool (MST) was carried out on the first day of admission. Patients with a positive screening were recruited to have a complete nutritional evaluation and intervention, following usual clinical practice. Nutritional evaluation was repeated after one week. RESULTS: Six hundred and seventeen hematological patients were screened (37.8% with positive screening). After one week, median diet intake increased from 80% to 90% (p < 0.001), and an increase of 407.36 Kcal (SD 679.37) and 17.58 g of protein (SD 31.97) was also achieved. More patients reached their energy and protein requirements (41.6 vs.% 63.3%, p = 0.009) and nutritional parameters remained stable. A trend to a lower stay (3.5 to 4.5 days less) was detected in the groups of patients who covered their needs. CONCLUSIONS: The implementation of early malnutrition screening and short nutritional interventions improved energy and protein intake, increasing the percentage of patients who meet their requirements and avoiding deterioration of nutritional status.

[The use of food supplements - beverages and concentrated food products in tablets made from plants in sanatory and health resort rehabilitation of patients with chronic pathology]. / Ispol'zovanie biologicheski aktivnykh dobavok k pishche - napitkov i tabletirovannykh kontsentrirovannykh pishchevykh produktov iz rastitel'nogo syr'ia pri sanatorno-kurortnoi reabilitatsii bol'nykh s khronicheskoi patologiei.

The effectiveness of a recovery complex optimization in conditions of the sanatorium-resort rehabilitation of patients with chronic pathology by provision of the dietotherapy ration balance on nutrients, the use of natural (of the plant raw material cryopowders in the form of teas and tableted forms) and the "Centrum" synthetic vitamin-mineral complexes, probiotics was substantiated and demonstrated.

[Evaluation of patient diet in sanatoria and health resorts]. / Otsenka ratsionov pitaniia bol'nykh v sanatorno-kurortnykh usloviiakh.

By the example of nutrition of patients from sanatorium "Kristall" (the Black Sea coast) an evaluation of patients nutrition in sanatoria and health resorts is made. It is determined, that the standard patients diets (Table N 15, 5, 10) do not differ from the reference ones regarding their calorie content, main food components and energy value. Though insufficient content of vitamins, unsaturated fatty acids and linoleic/linolein acids imbalance is marked.