Organizing glucose disposal: emerging roles of the glycogen targeting subunits of protein phosphatase-1

Glucose is stored in mammalian tissues in the form of glycogen. Glycogen levels are markedly reduced in liver or muscle cells of patients with insulin-resistant or insulin-deficient forms of diabetes, suggesting that impaired glycogen synthesis may contribute to development of hyperglycemia. Recently, interest in this area has been further stimulated by new insights into the spatial organization of metabolic enzymes within cells and the importance of such organization in regulation of glycogen metabolism. It is now clear that a four-member family of glycogen targeting subunits of protein phosphatase-1 (PP1) plays a major role in coordinating these events. These proteins target PP1 to the glycogen particle and also bind differentially to glycogen synthase, glycogen phosphorylase, and phosphorylase kinase, thereby serving as molecular scaffolds. Moreover, the various glycogen-targeting subunits have distinct tissue expression patterns and can influence regulation of glycogen metabolism in response to glycogenic and glycogenolytic signals. The purpose of this article is to summarize new insights into the structure, function, regulation, and metabolic effects of the glycogen-targeting subunits of PP1 and to evaluate the possibility that these molecules could serve as therapeutic targets for lowering of blood glucose in diabetes.     

Fabry disease and vascular risk factors: future strategies for patient-based studies and the knockout murine model

Fabry disease is secondary to deficiency of the lysosomal enzyme α-galactosidase A, leading to altered glycosphingolipid metabolism and accumulation that is often associated with endothelial dysfunction. Current evidence suggests that there is impairment of the vascular nitric oxide pathway, with abnormalities evident in the cerebral circulation and in the dermal vasculature of patients with Fabry disease. Some of these findings have been confirmed in a mouse model of Fabry disease. The murine model, however, allows investigation of Fabry disease at a non-clinical level and a near complete investigation of biological processes within an affected tissue. This is of particular utility in allowing gene expression analysis of clinically inaccessible tissues such as the aorta.
Conclusion: Future developments in array technology for proteins and DNA single nucleotide polymorphism analysis, together with gene expression microarray analysis, may open a new chapter in our understanding of the biology of lysosomal storage disorders.     

The heart string: a simple, inexpensive exposure of the heart during coronary artery operations

A method of heart retraction during coronary artery bypass operations is described. The technique improves exposure of the coronary arteries, especially of the circumflex and posterior descending coronary branches during grafting. In addition, it is simple, safe, and inexpensive. Furthermore, this technique can be applied for off-pump coronary artery bypass surgery.     

Update on muscle disease

Journal of Neurology - In this article, we highlight some of the most important developments from the last few years in the field of muscle diseases, including new additions to the congenital...     

Impact of Parent Practices of Infant Positioning on Head Orientation Profile and Development of Positional Plagiocephaly in Healthy Term Infants

Aims: The influence of infant positioning on the development of head orientation and plagiocephaly is not clear. This study explored the relationship between infant body and head positioning, with the development of asymmetrical head orientation and/or positional plagiocephaly. Methods: Clinician measurement of head orientation profile and parent-reported infant positioning data were collected for 94 healthy term infants at 3, 6, and 9 weeks of age. Plagiocephaly was measured at 9 weeks with the modified Cranial Vault Asymmetry Index. Results: More severe plagiocephaly was associated with longer supine-sleep-maximum (p = 0.001) and longer supine-lying-total (p = 0.014) at 6 weeks. Prone positioning was not associated with plagiocephaly. Parent-reported head asymmetry during awake and sleep time at 3 weeks identified infants with clinician-measured head asymmetry at 9 weeks. Better symmetry in head turning was associated with more side-lying-total time by 9 weeks (p = 0.013). Conclusions: Our results showed that infant positioning is associated with early head orientation and plagiocephaly development. Early parent-reported asymmetry during awake and sleep time is an important indicator for the need for professional assessment and advice. A Plagiocephaly Prevention Strategy and Plagiocephaly Screening Pathway are provided for clinicians and parents.     

Colorectal smartphone apps: opportunities and risks

Aim The increased utilization of smartphones within the clinical environment together with connected applications (apps) provides opportunity for doctors, including coloproctologists, to integrate such technology into clinical practice. However, the reliability of unregulated medical apps has recently been called into question. Here, we review contemporary medical apps specifically themed towards colorectal diseases and assess levels of medical professional involvement in their design and content. Method The most popular smartphone app stores (iPhone, Android, Blackberry, Nokia, Windows and Samsung) were searched for colorectal disease themed apps, using the disease terms colorectal cancer, Crohn’s disease, ulcerative colitis, diverticulitis, haemorrhoids, anal fissure, bowel incontinence and irritable bowel syndrome. Results A total of 68 individual colorectal themed apps were identified, amongst which there were five duplicates. Only 29% of colorectal apps had had customer satisfaction ratings and 32% had named medical professional involvement in their development or content. Conclusion The benefits of apps are offset by lack of colorectal specification. There is little medical professional involvement in their design. Increased regulation is required to improve accountability of app content.