Almanac 2012: Congenital heart disease. The national society journals present selected research that has driven recent advances in clinical cardiology

This Almanac highlights recent papers on congenital heart disease in the major cardiac journals. Over 100 articles are cited. Subheadings are used to group relevant papers and allow readers to focus on their areas of interest, but are not meant to be comprehensive for all aspects of congenital cardiac disease.     

Algo Used by Homecare Nonoccupational Therapists Selecting Bathing Assistive Technology: Enhancing Standardization by Exploring Clinical Reasoning

Algo is a clinical decision algorithm developed to support nonoccupational therapists in establishing assistive technology recommendations to enable physically disabled adults to perform their hygiene at home. This study aimed to explore the in-depth clinical reasoning of nonoccupational therapists using Algo to pinpoint the items leading to disagreements regarding recommendations. A multiple-case study was conducted with eight nonoccupational therapists trained to use Algo and filmed while using it with six standardized clients. Explicitation interviews were conducted for the conflicting recommendations. Identifying the key reasoning skills to develop in Algo users has led to three recommendations to enhance standardization with seniors.     

Crystal structure and functional mapping of human ASMT,the last enzyme of the melatonin synthesis pathway

Abstract: Melatonin is a synchronizer of many physiological processes. Abnormal melatonin signaling is associated with human disorders related to sleep, metabolism, and neurodevelopment. Here, we present the X‐ray crystal structure of human N‐acetyl serotonin methyltransferase (ASMT), the last enzyme of the melatonin biosynthesis pathway. The polypeptide chain of ASMT consists of a C‐terminal domain, which is typical of other SAM‐dependent O‐methyltransferases, and an N‐terminal domain, which intertwines several helices with another monomer to form the physiologically active dimer. Using radioenzymology, we analyzed 20 nonsynonymous variants identified through the 1000 genomes project and in patients with neuropsychiatric disorders. We found that the majority of these mutations reduced or abolished ASMT activity including one relatively frequent polymorphism in the Han Chinese population (N17K, rs17149149). Overall, we estimate that the allelic frequency of ASMT deleterious mutations ranges from 0.66% in Europe to 2.97% in Asia. Mapping of the variants on to the 3‐dimensional structure clarifies why some are harmful and provides a structural basis for understanding melatonin deficiency in humans.     

Folliculotropism in pigmented facial macules: Differential diagnosis with reflectance confocal microscopy

Pigmented facial macules are common on sun damage skin. The diagnosis of early stage lentigo maligna (LM) and lentigo maligna melanoma (LMM) is challenging. Reflectance confocal microscopy (RCM) has been proven to increase diagnostic accuracy of facial lesions. A total of 154 pigmented facial macules, retrospectively collected, were evaluated for the presence of already‐described RCM features and new parameters depicting aspects of the follicle. Melanocytic nests, roundish pagetoid cells, follicular infiltration, bulgings from the follicles and many bright dendrites and infiltration of the hair follicle (ie, folliculotropism) were found to be indicative of LM/LMM compared to non‐melanocytic skin neoplasms (NMSNs), with an overall sensitivity of 96% and specificity of 83%. Concerning NMSNs, solar lentigo and lichen planus‐like keratosis resulted better distinguishable from LM/LMM because usually lacking malignant features and presenting characteristic diagnostic parameters, such as epidermal cobblestone pattern and polycyclic papillary contours. On the other hand, distinction of pigmented actinic keratosis (PAK) resulted more difficult, and needing evaluation of hair follicle infiltration and bulging structures, due to the frequent observation of few bright dendrites in the epidermis, but predominantly not infiltrating the hair follicle (estimated specificity for PAK 53%). A detailed evaluation of the components of the folliculotropism may help to improve the diagnostic accuracy. The classification of the type, distribution and amount of cells, and the presence of bulging around the follicles seem to represent important tools for the differentiation between PAK and LM/LMM at RCM analysis.     

Association of salivary-assessed oxytocin and cortisol levels with time of night and sleep stage

There have been proposals for REM to have a function of emotional memory consolidation, and also for REM sleep to be involved in the promotion of attachment behaviour. The hormones cortisol and oxytocin, respectively, may be involved in these proposed REM sleep functions. However, there are conflicting reports on whether levels of cortisol differ between sleep stages when time since sleep onset (SSO) is controlled, and virtually no literature on whether levels of oxytocin differ between sleep stages. This study thus investigated the changes in levels of oxytocin (OT) and cortisol (CT) across the night, and whether these levels differ between REM and N2 sleep when time SSO is controlled. 20 participants (10 males, 10 females, mean age?=?20.45, SD?=?2.01) were awakened 10?min into REM and N2 sleep periods in the sleep laboratory and gave saliva samples which were assayed for OT and CT. Levels of OT were relatively constant across the night, whereas CT increased significantly. REM and N2 did not differ significantly neither for OT nor for CT. The study has implications for models of sleep-dependent memory consolidation that incorporate the late sleep increase in cortisol as a functional component of memory consolidation, and also for the medical diagnostic assaying of OT during sleep.     

Coenzyme Q10 supplementation reverses age-related impairments in spatial learning and lowers protein oxidation

Coenzyme Q10 (CoQ) is widely available as a dietary supplement and remains under consideration as a treatment for age-associated neurodegenerative conditions. However, no studies have determined if supplementation, initiated relatively late in life, could have beneficial effects on mild functional impairments associated with normal brain aging. Accordingly, the current study assessed the effect of CoQ intake in older mice for which cognitive and psychomotor impairments were already evident. Separate groups of young (3.5 months) and relatively old mice (17.5 months) were fed a control diet or a diet supplemented with low (0.72 mg/g) or high (2.81 mg/g) concentrations of CoQ for 15 weeks. After 6 weeks, the mice were given tests for spatial learning (Morris water maze), spontaneous locomotor activity, motor coordination, and startle reflex. Age-related impairments in cognitive and psychomotor functions were evident in the 17.5-month-old mice fed the control diet, and the low-CoQ diet failed to affect any aspect of the impaired performance. However, in the Morris water maze test, old mice on the high-CoQ diet swam to the safe platform with greater efficiency than the mice on the control diet. The old mice supplemented with the high-CoQ diet did not show improvement when spatial performance was measured using probe trials and failed to show improvement in other tests of behavioral performance. Protein oxidative damage was decreased in the mitochondria from the heart, liver, and skeletal muscle of the high-CoQ-supplemented mice and, to some extent, in the brain mitochondria. Contrasting with the deleterious effect of long-term CoQ supplementation initiated during young adulthood previously published, this study suggests that CoQ improves spatial learning and attenuates oxidative damage when administered in relatively high doses and delayed until early senescence, after age-related declines have occurred. Thus, in individuals with age-associated symptoms of cognitive decline, high-CoQ intake may be beneficial.