J. Clin. Med.2014, 3(3), 1050-1063; doi:10.3390/jcm3031050 - published 22 September 2014 Show/Hide Abstract
Abstract: Non-alcoholic fatty liver disease (NAFLD) impairs liver functions, the organ responsible for the regulation of endogenous glucose production and thus plays a key role in glycemic homeostasis. Therefore, interventions designed to normalize liver fat content are needed to improve glucose metabolism in patients affected by NAFLD such as obesity. Objective: this investigation is designed to determine the effects of caloric restriction on hepatic and peripheral glucose metabolism in obese humans with NAFLD. Methods: eight non-diabetic obese adults were restricted for daily energy intake (800 kcal) and low carbohydrate (<10%) for 8 weeks. Body compositions, liver fat and hepatic glucose production (HGP) and peripheral glucose disposal before and after the intervention were determined. Results: the caloric restriction reduced liver fat content by 2/3 (p = 0.004). Abdominal subcutaneous and visceral fat, body weight, BMI, waist circumference and fasting plasma triglyceride and free fatty acid concentrations all significantly decreased (p < 0.05). The suppression of post-load HGP was improved by 22% (p = 0.002) whereas glucose disposal was not affected (p = 0.3). Fasting glucose remained unchanged and the changes in the 2-hour plasma glucose and insulin concentration were modest and statistically insignificant (p > 0.05). Liver fat is the only independent variable highly correlated to HGP after the removal of confounders. Conclusion: NAFLD impairs HGP but not peripheral glucose disposal; low carbohydrate caloric restriction effectively lowers liver fat which appears to directly correct the HGP impairment.
J. Clin. Med.2014, 3(3), 1043-1049; doi:10.3390/jcm3031043 - published 18 September 2014 Show/Hide Abstract
Abstract: Oral urea has been used in the past to treat various diseases like gastric ulcers, liver metastases, sickle cell disease, heart failure, brain oedema, glaucoma, Meniere disease, etc. We have demonstrated for years, the efficacy of urea to treat euvolemic (SIADH) or hypervolemic hyponatremia. We briefly describe the indications of urea use in symptomatic and paucisymptomatic hyponatremic patients. Urea is a non-toxic, cheap product, and protects against osmotic demyelinating syndrome (ODS) in experimental studies. Prospective studies showing the benefit to treat mild chronic hyponatremia due to SIADH and comparing water restriction, urea, high ceiling diuretics, and antivasopressin antagonist antagonist should be done.
J. Clin. Med.2014, 3(3), 1033-1042; doi:10.3390/jcm3031033 - published 15 September 2014 Show/Hide Abstract
Abstract: To date, preconceptual and prenatal patients have been offered gene-by-gene, disorder-by-disorder carrier screening. Newer techniques allow screening of many disorders at one time. The goal of this review is to provide an overview of the current practice and future direction of carrier screening within the preconceptual/prenatal setting.
J. Clin. Med.2014, 3(3), 1018-1032; doi:10.3390/jcm3031018 - published 12 September 2014 Show/Hide Abstract
Abstract: Prenatal genetic screening and testing provides prospective parents information about the health of their fetus. It is offered to find or address an increased risk for chromosomal abnormalities or other genetic conditions in the fetus or to identify the cause of fetal structural abnormalities detected by prenatal imaging. Genome-wide tests, such as the already widely-used chromosomal microarray analysis and emerging diagnostic whole exome and whole genome sequencing, have improved the ability to detect clinically significant findings, but have also increased the chance of detecting incidental findings and variants of uncertain significance. There is an extensive ongoing discussion about optimal strategies for diagnostic laboratories to report such findings and for providers to communicate them with patients. While consensus opinions and guidelines are beginning to appear, they often exclude the prenatal setting, due to its unique set of challenging considerations. These include more limited knowledge of the impact of genetic variants when prospectively detected in an ongoing pregnancy, the absence or limitations of detecting clinically recognizable phenotypes at the time of testing and the different decision-making processes that will ensue from testing. In this review, we examine these challenges within the medical ethical framework unique to prenatal care.
J. Clin. Med.2014, 3(3), 997-1017; doi:10.3390/jcm3030997 - published 5 September 2014 Show/Hide Abstract
Abstract: Tens of millions of patients are affected by liver disease worldwide. Many of these patients can benefit from cell therapy involving living metabolically active cells, either by treatment of their liver disease, or by prevention of their disease phenotype. Cell therapies, including hepatocyte transplantation and bioartificial liver (BAL) devices, have been proposed as therapeutic alternatives to the shortage of transplantable livers. Both BAL and hepatocyte transplantation are cellular therapies that avoid use of a whole liver. Hepatocytes are also widely used in drug screening and liver disease modelling. However, the demand for human hepatocytes, heavily outweighs their availability by conventional means. Induced pluripotent stem cells (iPSCs) technology brings together the potential benefits of embryonic stem cells (ESCs) (i.e., self-renewal, pluripotency) and addresses the major ethical and scientific concerns of ESCs: embryo destruction and immune-incompatibility. It has been shown that hepatocyte-like cells (HLCs) can be generated from iPSCs. Furthermore, human iPSCs (hiPSCs) can provide an unlimited source of human hepatocytes and hold great promise for applications in regenerative medicine, drug screening and liver diseases modelling.Despite steady progress, there are still several major obstacles that need to be overcome before iPSCs will reach the bedside. This review will focus on the current state of efforts to derive hiPSCs for potential use in modelling and treatment of liver disease.
J. Clin. Med.2014, 3(3), 986-996; doi:10.3390/jcm3030986 - published 5 September 2014 Show/Hide Abstract
Abstract: First-trimester sonographic assessment of the risk of chromosomal abnormalities is routinely performed throughout the world, primarily by measuring fetal nuchal translucency thickness between 11–13 weeks’ gestation, combined with assessment of serum markers. The development of high-frequency transvaginal transducers has led to improved ultrasound resolution and better visualization of fetal anatomy during the first-trimester. Continuous improvement in ultrasound technology allows a thorough detailed assessment of fetal anatomy at the time of the nuchal translucency study. Using transabdominal or transvaginal sonography, or a combination of both approaches, it is now possible to diagnose a wide range of fetal anomalies during the first trimester. Multiple studies reported early diagnosis of major fetal anomalies after demonstrating the association of increased nuchal translucency thickness with structural defect in chromosomally normal and abnormal fetuses. Normal sonographic findings provide reassurance for women at high risk while detection of fetal malformation during the first trimester enables discussion and decisions about possible treatments and interventions, including termination of pregnancy, during an early stage of pregnancy.