The incretin effect and its potentiation by glucagon-like peptide 1-based therapies: a revolution in diabetes management

The incretin effect is a phenomenon in which enteral glucose administration provokes greater insulin secretion than intravenous administration. The main incretins, glucose-dependent insulinotropic peptide and glucagon-like peptide (GLP)-1 are defective in Type 2 diabetes; whereas glucose-dependent insulinotropic peptide displays diminished effectiveness, GLP-1 secretion is decreased; thus, GLP-1 was a stronger candidate for a new class of anti-diabetic agents designed to potentiate the incretin effect. In the past decade, GLP-1 mimetics, peptidase inhibitors and GLP-1 have been developed. Early randomised trials show that these agents contribute to glucose homeostasis and enhance beta-cell function, without causing hypoglycaemia or weight gain. This review includes an historical perspective, physiology of incretins, and discussions of the pathophysiology in Type 2 diabetes, pharmacology of the main agents and randomised clinical trials published to date.     

Social Work Admission Assessment Tool for identifying patients in need of comprehensive social work evaluation

Early identification of patients who need a social work evaluation is integral to effective discharge planning. This article describes the development and application of the Social Work Admission Assessment Tool (SWAAT), a six-item scale that identifies patients with complicated discharge needs who require a social work evaluation. It addresses ambulation, mental status, living situation, current social services, self-perceived need for additional services, and need for assistance in going home. Based on their scores, patients are categorized as having low, intermediate, or high need. A greater proportion of high-need patients were discharged with services and had prolonged hospitalizations (p = .0001). The SWAAT is a comprehensive needs assessment tool that may facilitate discharge planning and improve quality of care.     

Neuroimaging and cardiac correlates of cognitive function among patients with cardiac disease

In the present study, we examined the relationships between whole brain volume (WBV), subcortical hyperintensities (SH), indices of cardiac disease and cognitive function in nondemented cardiac patients with evidence of mild cerebrovascular disease. A total of 27 individuals with evidence of cardiac disease underwent neuropsychological examination, neuroimaging, and cardiac assessment. Cognition was assessed with the Dementia Rating Scale-2 (DRS). WBV and SH were quantified using a semi-automated thresholding program based on MRI. Correlational analyses revealed that WBV predicted performance on the overall DRS score, the attention subscale and the initiation/perseveration scale. SH were significantly associated with performance on the attention subscale, and the initiation/perseveration subscale. Regression analyses revealed that SH accounted for most of the variance in the initiation/perseveration scale, whereas WBV accounted for most of the variance in the attention scale. The only cardiac structural or functional variable related to the neurological indices was aortic diameter, which was strongly related to both neuroimaging variables, as well as performances on the DRS attention and initiation/perseveration subscales. Our results highlight the importance of overall brain parenchyma in determining cognitive status among patients at risk for cognitive decline and suggest that select indices of structural cardiac morphology may be related to the early phases of cerebrovascular disease and cognitive status.     

Vertebral bone mineral density, marrow perfusion, and fat content in healthy men and men with osteoporosis: dynamic contrast-enhanced MR imaging and MR spectroscopy

PURPOSE: To prospectively use hydrogen 1 (1H) magnetic resonance (MR) spectroscopy and dynamic contrast material-enhanced MR imaging to measure vertebral body marrow fat content and bone marrow perfusion in older men with varying bone mineral densities as documented with dual x-ray absorptiometry (DXA). MATERIALS AND METHODS: This study had institutional review board approval, and all participants provided informed consent. DXA, 1H MR spectroscopy, and dynamic contrast-enhanced MR imaging of the lumbar spine were performed in 90 men (mean age, 73 years; range, 67-101 years). Vertebral marrow fat content and perfusion (maximum enhancement and enhancement slope) were compared for subject groups with differing bone densities (normal, osteopenic, and osteoporotic). The t test was used for comparisons between groups, and the Pearson test was used to determine correlation between marrow fat content and perfusion indexes. RESULTS: Eight subjects were excluded, yielding a final cohort of 82 subjects (mean age, 73 years; range, 67-101 years) that included 42 subjects with normal bone density (mean T score, 0.8 +/- 1.1 [standard deviation]), 23 subjects with osteopenia (mean T score, -1.6 +/- 0.4), and 17 subjects with osteoporosis (mean T score, -3.2 +/- 0.5). Vertebral marrow fat content was significantly increased in subjects with osteoporosis (mean fat content, 58.23% +/- 7.8) (P = .002) or osteopenia (mean fat content, 55.68% +/- 10.2) (P = .034) compared with that in subjects with normal bone density (50.45% +/- 8.7). Vertebral marrow perfusion indexes were significantly decreased in osteoporotic subjects (mean enhancement slope, 0.78%/sec +/- 0.3) compared with those in osteopenic subjects (mean enhancement slope, 1.15%/sec +/- 0.6) (P = .007) and those in subjects with normal bone density (mean enhancement slope, 1.48%/sec +/- 0.7) (P < .001). CONCLUSION: Subjects with osteoporosis have decreased vertebral marrow perfusion and increased marrow fat compared with these parameters in subjects with osteopenia. Similarly, subjects with osteopenia have decreased vertebral marrow perfusion and increased marrow fat compared with these parameters in subjects with normal bone density.     

Visual neglect: occurrence and patterns in pilots in a simulated overnight flight

INTRODUCTION: Visual neglect is the unconscious inability to recognize or acknowledge some visual information in the presence of a structurally intact visual system, and was hypothesized to occur with less than 24 h of continuous wakefulness. Visual perception was evaluated in military pilots during a simulated overnight flight to explore for the possible occurrence of visual neglect. METHODS: There were eight military pilots (male, 31-52 yr of age, mean 37 yr) on flight status who were recruited to perform the primary task of flying a simulated 12.5 h overnight mission after a day of continuous wakefulness and the secondary task of responding to repeated 20 min presentations of single- and double-light stimuli displayed in random sequence at 15 degrees intervals across the cockpit instrument panel. In addition to the visual performance task, simulator shutdowns occurring when the tolerances of the simulator were exceeded were measured and simple reaction time on the psychomotor vigilance task was assessed. Total continuous wakefulness was 26.5 h. RESULTS: Combined performance on the visual perception task showed response omissions increasing at 19 h of continuous wakefulness. Patterns included omissions at all stimulus locations, of primarily peripherally located stimuli, and of one of two simultaneously presented stimuli. Simulator shutdowns began at 21.5 h of continuous wakefulness. Correlation of visual task response omissions with simulator shutdowns was r = 0.95, p < 0.0001. CONCLUSIONS: Significant neglect of visual stimuli occurred in pilots beginning at 19 h of continuous wakefulness in a simulated overnight fixed wing aircraft flight, preceded simulator shutdowns, and correlated at 0.95 with simulator shutdowns.     

Greek employee awareness of carcinogenic exposure

BACKGROUND: Occupational risk factors contribute significantly to the development of lung cancer; however, little is known about the extent to which employees are informed of occupational exposure to carcinogenic substances. METHODS: Through a case-control study, we estimated the level of awareness among Greek employees potentially exposed to known carcinogenic substances within various occupational settings. RESULTS: Only 6.6% of men (n = 482) employed in occupations with potential exposure to carcinogenic substances were aware of such occupational exposures. Age, education, and residence were significantly associated with awareness. Employees having at least a secondary level of education were 3.5 times more aware than those having at most 6 years of educational training. CONCLUSIONS: Assessing awareness among workers potentially exposed to occupational risk factors and promoting occupational health education are important steps for increasing health and safety at the workplace.     

Xanthophylls and alpha-tocopherol decrease UVB-induced lipid peroxidation and stress signaling in human lens epithelial cells

Epidemiological studies suggest that consumption of vegetables rich in the xanthophylls lutein (LUT) and zeaxanthin (ZEA) reduces the risk for developing age-related cataract, a leading cause of vision loss. Although LUT and ZEA are the only dietary carotenoids present in the lens, direct evidence for their photoprotective effect in this organ is not available. The present study examined the effects of xanthophylls and alpha-tocopherol (alpha-TC) on lipid peroxidation and the mitogen-activated stress signaling pathways in human lens epithelial (HLE) cells following ultraviolet B light (UVB) irradiation. When presented with LUT, ZEA, astaxanthin (AST), and alpha-TC as methyl-beta-cyclodextrin complexes, HLE cells accumulated the lipophiles in a concentration- and time-dependent manner with uptake of LUT exceeding that of ZEA and AST. Pretreatment of cultures with either 2 micromol/L xanthophyll or 10 micromol/L alpha-TC for 4 h before exposure to 300 J/m(2) UVB radiation decreased lipid peroxidation by 47-57% compared with UVB-treated control HLE cells. Pretreatment with the xanthophylls and alpha-TC also inhibited UVB-induced activation of c-JUN NH(2)-terminal kinase (JNK) and p38 by 50-60 and 25-32%, respectively. There was substantial inhibition of UVB-induced JNK and p38 activation for cells containing <0.20 and approximately 0.30 nmol xanthophylls/mg, respectively, whereas >2.3 nmol alpha-TC/mg protein was required to significantly decrease UVB-induced stress signaling. These data suggest that xanthophylls are more potent than alpha-TC for protecting human lens epithelial cells against UVB insult.     

Risk of non-medullary thyroid cancer influenced by polymorphic variation in the thyroglobulin gene

Benign thyroid disorders are strong risk factors for non-medullary thyroid cancer (NMTC). Germline variation in Tg (thyroglobulin) and TSHR (thyroid stimulating hormone receptor) confers an increased risk of benign thyroid disorders. To explore the hypothesis that polymorphic variation in these genes affects the risk of NMTC we compared the frequency of TgQ2511R, TSHR-P52T and TSHR-D727E genotypes in two series of NMTC cases and controls (group 1, Canadian 102 cases and 102 controls; group 2, British 202 cases and 298 controls). No significant association was seen with TSHR-P52T and TSHR-D727E genotypes and risk of NMTC. However, the frequency of the R-allele of TgQ2511R was over represented in NMTC cases in both study populations. The odds ratios associated with hetero- and homozygosity for the R-allele were 1.6 (95% confidence interval, 1.1-2.5) and 2.0 (95% confidence interval, 1.2-3.3), respectively. Although the risk of NMTC associated with the TgQ2511R R-allele is modest, its high prevalence in the general population suggests it may make a significant contribution to the incidence of NMTC.