An RNA Polymerase III General Transcription Factor Engages in Cell Type-Specific Chromatin Looping

Transcription factors (TFs) bind DNA in a sequence-specific manner and are generally cell type-specific factors and/or developmental master regulators. In contrast, general TFs (GTFs) are part of very large protein complexes and serve for RNA polymerases’ recruitment to promoter sequences, generally in a cell type-independent manner. Whereas, several TFs have been proven to serve as anchors for the 3D genome organization, the role of GTFs in genome architecture have not been carefully explored. Here, we used ChIP-seq and Hi-C data to depict the role of TFIIIC, one of the RNA polymerase III GTFs, in 3D genome organization. We find that TFIIIC genome occupancy mainly occurs at specific regions, which largely correspond to Alu elements; other characteristic classes of repetitive elements (REs) such as MIR, FLAM-C and ALR/alpha are also found depending on the cell’s developmental origin. The analysis also shows that TFIIIC-enriched regions are involved in cell type-specific DNA looping, which does not depend on colocalization with the master architectural protein CTCF. This work extends previous knowledge on the role of TFIIIC as a bona fide genome organizer whose action participates in cell type-dependent 3D genome looping via binding to REs

Osteopathia Striata with Cranial Sclerosis: Genetic Diagnosis in a Rural Setting

Osteopathia striata with cranial sclerosis (OSCS) is a rare skeletal dysplasia inherited in an X-linked dominant pattern. Patients present with a wide variety of congenital anomalies such as craniofacial, cardiac, musculoskeletal, intestinal, and genitourinary abnormalities, and developmental delay. The genetic mutation causes increased ossification of bones which can compress cranial nerves and subsequently lead to acquired hearing loss, facial paralysis, and other neurologic defects. OSCS has also been associated with epileptic seizures, pyloric stenosis, hypothyroidism, and increased bone fragility. Due to the nonspecific presentation of conditions like OSCS and the serious complications it predisposes patients to, it is important that children undergo early genetic testing to confirm the diagnosis of such conditions. Genetic testing and similar services are especially limited in rural and underserved areas and this significantly impacts patient care, particularly for the pediatric population. This case describes a child with limited access to nearby genetic services presenting with multiple unexplained congenital abnormalities who was ultimately diagnosed with OSCS following genetic testing. It describes the clinical presentation of a rare condition and highlights the significantly protracted process of genetic testing for patients in underserved areas without access to genetic services and why providers must be aware of these healthcare disparities and how they affect patients

Control del dolor agudo en emergencias médicas

El dolor agudo es motivo de consulta frecuente en emergencias médicas y de manera general es inadecuadamente evaluado y tratado, ocasionando persistencia del dolor, u oligoanalgesia. El objetivo de este estudio fue evaluar la respuesta analgésica del dolor agudo a la administración intranasal de ketamina. Fueron evaluados 116 pacientes que acudieron con dolor agudo al Servicio de Emergencias del Hospital Básico Sudamericano entre enero 2015 a julio 2016. de manera subjetiva mediante la escala visual análoga (EVA) y de manera objetiva mediante la escala porcentual numérica (NRS), consiguiendo el control eficaz del dolor agudo de elevada y moderada intensidad, con pocos efectos deletéreos. Consecuentemente se puede concluir que el uso de ketamina intranasal en pacientes con dolor agudo es una excelente alternativa de tratamiento por su acción efectivo y por su costo

Environmental Impact on Metabolism

The prevalence of obesity and type 2 diabetes (T2D) is dramatically increasing worldwide during the last few decades. This phenomenon is mostly due to lifestyle factors (sedentariness, noxious food), along with genetic susceptibility. Recent evidence points out the role of endocrine-disrupting chemicals (EDCs) having obesogenic and/or diabetogenic properties that may also play a pathophysiological role in the occurrence of metabolic diseases. Both experimental and epidemiological evidence support a role for early and chronic exposure to EDCs with endocrine- and metabolic-disrupting effects. Most of them are present in the food chain and are stored in the fat mass after absorption. Each of them may act through several pathways; among them, the disruption of gut microbiota has been identified as one of the mechanisms through which EDCs exposure can promote obesity and T2D. Therefore, this chapter summarizes the evidence regarding the EDCs with obesogenic and/or diabetogenic characteristics and their properties to blunt metabolic health through the disruption of gut microbiota

Clinical and nutritional management of very-low-calorie ketogenic diet (VLCKD) in patients with psoriasis and obesity: a practical guide for the nutritionist

Psoriasis is an immune-mediated inflammatory skin disease associated with multiple comorbidities. Considered one of the most common inflammatory skin diseases among the general population, it not only affects the skin, but also negatively impacts other organs and joints. In addition, psoriasis has been associated with several chronic cardio-metabolic diseases such as obesity, which would seem to be (i) a risk factor for the onset of psoriasis and (ii) a worsening factor of the severity of the disease. Weight loss appears to improve severity in overweight patients. Recently proposed as an obesity management nutritional strategy, the very-low-calorie ketogenic diet (VLCKD) has demonstrated significant effects in reducing inflammatory processes. In the current review, we describe the evidence available on psoriasis and VLCKD, and provide a practical guide to the prescription of VLCKD in the different phases, evaluation and management of possible adverse events, and the importance of physical activity as a lifestyle modification to reduce psoriasis and associated comorbidities. Randomized control trials are, however, necessary to determine the most effective VLCKD protocol for patients with obesity and psoriasis, optimal protocol duration, composition of micronutrients and macronutrients, choice of special supplements, and management of carbohydrate reintroduction