Epigenome Modulation Induced by Ketogenic Diets

Ketogenic diets (KD) are dietary strategies low in carbohydrates, normal in protein, and high, normal, or reduced in fat with or without (Very Low-Calories Ketogenic Diet, VLCKD) a reduced caloric intake. KDs have been shown to be useful in the treatment of obesity, metabolic diseases and related disorders, neurological diseases, and various pathological conditions such as cancer, nonalcoholic liver disease, and chronic pain. Several studies have investigated the intracellular metabolic pathways that contribute to the beneficial effects of these diets. Although epigenetic changes are among the most important determinants of an organism’s ability to adapt to environmental changes, data on the epigenetic changes associated with these dietary pathways are still limited. This review provides an overview of the major epigenetic changes associated with KDs.     

Cross‐sector emergency planning for water supply utilities and healthcare facilities

The purpose of this article is to outline the criticality of water supply in sustained operations of healthcare facilities, particularly during community emergencies, and to advocate for enhanced cross‐sector support from the water utilities in meeting this need. Information and ideas presented here were developed in the course of a regional project sponsored by the Metropolitan Washington Council of Governments (MWCOG) for development of emergency water supply operations plans for critical water uses in the Washington, DC, area.     

Epidermal growth factor receptor in human brain tumors.

The expression of epidermal growth factor receptor (EGF-R) was examined in 27 primary human brain tumors (7 glioblastomas, 10 astrocytomas, 5 oligodendrogliomas, 1 schwannoma, 1 ganglioneuroma, 1 medulloblastoma, 1 ependymoma, 1 histiocytic lymphoma), in 6 brain metastases from lung carcinomas and in 20 meningiomas. Peritumoral tissues histologically normal excised surgically along with a large tumor were used as control. All plasma membranes from brain tissues tested showed specific EGF binding. The EGF receptor is expressed at low levels in the control human brain and at very high levels in 60% of the total intracranial tumors studied. When the various histological types of tumors were analyzed, the higher percentage of positive tumors was found with the meningiomas (85%) and the glioblastomas (71%), while the lower percentage of positivity was found with the oligodendrogliomas (40%) and the astrocytomas (30%). A good correlation between binding and total amount of EGF-R protein detected by Western Blot was also observed.     

Allergen immunotherapy for respiratory allergy: Quality appraisal of observational comparative effectiveness studies using the REal Life Evidence AssessmeNt Tool. An EAACI methodology committee analysis

BackgroundObservational comparative effectiveness studies in allergen immunotherapy (AIT) represent an important evidence source answering research questions that can be challenging to obtain from randomized controlled trials (RCTs), such as long‐term benefits of AIT, the effects on asthma prevention and the onset of new allergen sensitizations. However, observational studies are prone to several sources of bias, which limit their reliability.The REal Life Evidence AssessmeNt Tool (RELEVANT) was recently developed to assist in quality appraisal of observational comparative research to enable identification of useful nonrandomized studies to be considered within guideline development.ObjectiveTo systematically appraise the quality of published observational comparative AIT studies using RELEVANT.MethodsObservational studies comparing AIT to pharmacotherapy for respiratory allergies, assessing as outcome measures reduction of symptoms and/or medication use reduction, were retrieved by computerized bibliographic searches. According to RELEVANT, a failure to meet any one of primary items (background, design, measures, analysis, results, discussion/interpretation, and conflict of interest) represents a critical flaw, significantly undermining the validity of the study results.ResultsThe 14 studies identified supported the benefit of AIT in real‐life, which persists after treatment discontinuation. However, none of them met all the 7 primary RELEVANT criteria. The main defects were reported in the design (28.6% of studies), measures and analysis (64.3% of studies), and results (78.6% of studies) items, due to selection bias and lack of methods for adjusting controls. Half of the studies did not report on conflict of interest.ConclusionThere is a need for more robust observational research in AIT. RELEVANT appears as an easy‐to‐use and sensitive tool for quality appraisal in AIT studies.     

Value of exercise stress test, radionuclide angiography and coronary angiography in predicting new coronary events in asymptomatic patients after a first episode of myocardial infarction.

One-hundred-and-fifty-five consecutive symptom-free patients underwent maximal treadmill exercise testing, rest and stress radionuclide angiography at least two months after an uncomplicated acute myocardial infarction; of these, 90 underwent coronary angiography. All patients were followed-up for a mean of 32 +/- 13 months regarding the prediction of hard (death and reinfarction) and soft (angina and coronary surgery) coronary events. The specificity, sensitivity, positive and negative predictive value of exercise stress test were 47%, 76% and 41% for any coronary events; none of the patients who incurred a hard coronary event showed ischemia during electrocardiographic exercise tests. Sensitivity, specificity and positive predictive value for failure to increase the ejection fraction of at least 5% were 60%, 45% and 30% for any coronary event and 25%, 49% and 2% for any hard coronary event. The presence of multivessel disease at coronary angiography showed a sensitivity of 62% for any coronary event and of 67% for hard coronary events; specificities were 66% and 57%, and predictive values were 52% and 10%, respectively. It is concluded that electrocardiographic exercise testing, radionuclide angiography and coronary angiography are not helpful two months after an episode of uncomplicated myocardial infarction in order to identify patients who will suffer a new coronary event.     

Native associations of early hematopoietic stem cells and stromal cells isolated in bone marrow cell aggregates

In suspensions of murine bone marrow, many stromal cells are tightly entwined with hematopoietic cells. These cellular aggregations appear to exist normally within the marrow. Previous studies showed that lymphocytes and stem cells adhered to stromal cells via vascular cell adhesion molecule 1 (VCAM1). Injection of anti-VCAM1 antibody into mice disrupts the aggregates, showing the importance of VCAM1 in the adhesion between stromal cells and hematopoietic cells in vivo. Early hematopoietic stem cells were shown to be enriched in aggregates by using a limiting-dilution culture assay. Myeloid progenitors responsive to WEHI-3CM in combination with stem cell factor (c-kit ligand) and B220- B-cell progenitors responsive to insulin-like growth factor-1 in combination with interleukin-7 are not enriched. We propose a scheme of stromal cell-hematopoietic cell interactions based on the cell types selectively retained within the aggregates. The existence of these aggregates as native elements of bone marrow organization presents a novel means to study in vivo stem cell-stromal cell interaction.