How many forms of perseveration? Evidence from cancellation tasks in right hemisphere patients

Neglect patients' performance during cancellation tasks is characterized by left sided omissions and, in many cases, by the production of inappropriate material of various kinds in the ipsilesional space, e.g. additional marks over already cancelled targets, marks drawn away from targets, scribbles, irrelevant drawings. It is unclear whether these behaviours, which have collectively been called perseverative, are functionally and anatomically connected and whether they correlate with the severity of neglect. Here we report a retrospective study on 33 right brain damaged patients with neglect after right hemisphere lesions in whom we measured the intensity of perseveration of the three following kinds: (1) ‘additional marks' (AM) perseveration where patients cancelled a target with two or more well separated marks; (2) ‘scribble’ perseveration, where patients, instead of cancelling the target with a single pen stroke as required by the task, performed multiple pen strokes without breaking the pen-to-paper contact, with the final product being a scribble; (3) ‘flying marks’ (FM) perseveration where patients produced cancellation marks well away from the targets. We found that AM and FM perseveration correlated with neglect severity, while ‘scribble’ perseveration did not. The lesion-symptom mapping showed three separate anatomical areas in the right hemisphere: ‘scribble’ perseveration was associated with lesions of the orbitofrontal cortex and caudate nucleus; AM perseveration was associated with damage to the rolandic operculum, superior temporal gyrus and inferior frontal gyrus; FM perseveration was associated with damage to the dorsal premotor cortex and the temporal pole. Neglect severity followed damage to a region which grossly corresponds to the sum of the regions associated with AM and FM perseveration respectively. This complex behavioural and anatomical pattern is interpreted in terms of a three-factor model, in which AM perseveration is caused by a deficit of disengagement of attention from the right side (also causing omissions), FM perseveration is caused by directional hypokinesia (also causing left-side omissions), and ‘scribble’ perseveration is the consequence of a failure to inhibit an initiated motor act, which is completely separate (both anatomically and functionally) from the disorder inducing omissions.     

High prevalence of obesity among nursing personnel working in tertiary care hospital

Aim

To find out the prevalence of obesity and glucose intolerance among nurses working in tertiary care hospital.

新疆维吾尔族空腹血糖受损人群血脂水平变化及低密度脂蛋白胆固醇升高的相关因素分析

目的 分析新疆维吾尔族（维族）IFG人群血脂代谢状况及LDL-C升高的危险因素。 方法 对新疆地区2053例30～80岁维族居民行横断面调查,筛查IFG人群,分析血脂代谢状况及LDL-C相关危险因素。 结果 该IFG人群中,血脂代谢异常的总患病率为99.8%（613/614）。高TG血症患病率为85.5%（525/614）,男女比较,差异无统计学意义（P〉0.05）;高TC血症、高LDL-C血症患病率为72.5%（445/614）和40.7%（250/614）,男性高于女性（75.0% vs 70.1%,52.4% vs 29.9%,P〈0.05）;低HDL-C血症患病率为29.8%（183/614）,男性低于女性（28.0% vs 31.4%,P〈0.05）。Logistic回归分析显示,LDL-C升高的危险因素为年龄、TC、2 hPG。 结论 维族IFG人群血脂代谢异常的总患病为99.8%,其中LDL-C升高的患病率为40.7%,其危险因素为年龄、TC和2 hPG。     

Concepts in context: Processing mental state concepts with internal or external focus involves different neural systems

According to embodied cognition theories, concepts are contextually situated and grounded in neural systems that produce experiential states. This view predicts that processing mental state concepts recruits neural regions associated with different aspects of experience depending on the context in which people understand a concept. This neuroimaging study tested this prediction using a set of sentences that described emotional (e.g., fear, joy) and nonemotional (e.g., thinking, hunger) mental states with internal focus (i.e., focusing on bodily sensations and introspection) or external focus (i.e., focusing on expression and action). Consistent with our predictions, data suggested that the inferior frontal gyrus, a region associated with action representation, was engaged more by external than internal sentences. By contrast, the ventromedial prefrontal cortex, a region associated with the generation of internal states, was engaged more by internal emotion sentences than external sentence categories. Similar patterns emerged when we examined the relationship between neural activity and independent ratings of sentence focus. Furthermore, ratings of emotion were associated with activation in the medial prefrontal cortex, whereas ratings of activity were associated with activation in the inferior frontal gyrus. These results suggest that mental state concepts are represented in a dynamic way, using context-relevant interoceptive and sensorimotor resources.     

Ethnic disparities in the association of impaired fasting glucose with the 10-year cumulative incidence of type 2 diabetes

Aims

Evidence of ethnic disparities in the conversion of prediabetes to type 2 diabetes is scarce. We studied the association of impaired fasting glucose (IFG) and fasting plasma glucose (FPG) with the 10-year cumulative incidence of type 2 diabetes in three ethnic groups.

Methods

We analyzed data for 90 South-Asian Surinamese, 190 African-Surinamese, and 176 ethnic Dutch that were collected in the periods 2001–2003 and 2011–2012. We excluded those with type 2 diabetes or missing FPG data. We defined baseline IFG as FPG of 5.7–6.9 mmol/L. We defined type 2 diabetes at follow-up as FPG ≥ 7.0 mmol/L, HbA1c ≥ 48 mmol/mol (6.5%), or self-reported type 2 diabetes.

Results

10-Year cumulative incidences of type 2 diabetes were: South-Asian Surinamese, 18.9%; African-Surinamese, 13.7%; ethnic Dutch, 4.5% (p < 0.05). The adjusted association of baseline IFG and FPG with the 10-year cumulative incidence of type 2 diabetes was stronger for South-Asian Surinamese than for African-Surinamese and ethnic Dutch. The IFG (compared to normoglycaemia) ORs were 11.1 [3.0–40.8] for South-Asian Surinamese, 5.1 [2.0–13.3] for African-Surinamese, and 2.2 [0.5–10.1] for ethnic Dutch.

Conclusions

The 10-year cumulative incidence of type 2 diabetes was higher and associations with baseline IFG and FPG were stronger among South-Asian Surinamese and African-Surinamese than among ethnic Dutch. Our findings confirm the high risk of type 2 diabetes in South-Asians and suggest more rapid conversion in populations of South-Asian origin and (to a lesser extent) African origin than European origin.     

GCK-MODY diabetes as a protein misfolding disease: The mutation R275C promotes protein misfolding,self-association and cellular degradation

GCK-MODY, dominantly inherited mild hyperglycemia, is associated with more than 600 mutations in the glucokinase gene. Different molecular mechanisms have been shown to explain GCK-MODY. Here, we report a Pakistani family harboring the glucokinase mutation c.823C > T (p.R275C). The recombinant and in cellulo expressed mutant pancreatic enzyme revealed slightly increased enzyme activity (k_cat) and normal affinity for α-D-glucose, and resistance to limited proteolysis by trypsin comparable with wild-type. When stably expressed in HEK293 cells and MIN6 β-cells (at different levels), the mutant protein appeared misfolded and unstable with a propensity to form dimers and aggregates. Its degradation rate was increased, involving the lysosomal and proteasomal quality control systems. On mutation, a hydrogen bond between the R275 side-chain and the carbonyl oxygen of D267 is broken, destabilizing the F260-L271 loop structure and the protein. This promotes the formation of dimers/aggregates and suggests that an increased cellular degradation is the molecular mechanism by which R275C causes GCK-MODY.     

Glucoregulatory function among African Americans and European Americans with normal or pre-diabetic hemoglobin A1c levels

Objective

A hemoglobin (Hb) A1c range of 5.7%–6.4% has been recommended for the diagnosis of prediabetes. To determine the significance of such “prediabetic” HbA1c levels, we compared glucoregulatory function in persons with HbA1c levels of 5.7%–6.4% and those with HbA1c < 5.7%.

Methods

We studied 280 nondiabetic adults (142 black, 138 white; mean (± SD) age 44.2 ± 10.6 years). Each subject underwent clinical assessment, blood sampling for HbA1c measurement, and a 75-g oral glucose tolerance test at baseline. Additional assessments during subsequent outpatient visits included insulin sensitivity, using homeostasis model assessment (HOMA)-IR and the hyperinsulinemic euglycemic clamp; insulin secretion, using HOMA-B and frequently samples intravenous glucose tolerance test (FSIVGTT) and disposition index (DI); and measurement of fat mass, using DXA.

Results

Compared to subjects with HbA1c < 5.7%, persons with HbA1c levels of 5.7%–6.4% were older, and had higher body mass index (BMI) and insulin secretion but similar insulin sensitivity. When the two groups were matched in age and BMI, persons with HbA1c 5.7%–6.4% were indistinguishable from those with HbA1c < 5.7% with regard to all measures of glycemia and glucoregulatory function.

Conclusions

Unlike glucose-defined prediabetes status, an HbA1c range of 5.7%–6.4% does not reliably identify individuals with impaired insulin action or secretion, the classical defects underlying the pathophysiology of prediabetes. Thus, HbA1c cannot validly replace blood glucose measurement in the diagnosis of prediabetes. If utilized as a screening test due to convenience, aberrant HbA1c values should be corroborated with blood glucose measurement before therapeutic intervention.     

The natural history of nonalcoholic fatty liver disease: a population-based cohort study

BACKGROUND & AIMS: The natural history of nonalcoholic fatty liver disease (NAFLD) in the community remains unknown. We sought to determine survival and liver-related morbidity among community-based NAFLD patients. METHODS: Four hundred twenty patients diagnosed with NAFLD in Olmsted County, Minnesota, between 1980 and 2000 were identified using the resources of the Rochester Epidemiology Project. Medical records were reviewed to confirm diagnosis and determine outcomes up to 2003. Overall survival was compared with the general Minnesota population of the same age and sex. RESULTS: Mean (SD) age at diagnosis was 49 (15) years; 231 (49%) were male. Mean follow-up was 7.6 (4.0) years (range, 0.1-23.5) culminating in 3192 person-years follow-up. Overall, 53 of 420 (12.6%) patients died. Survival was lower than the expected survival for the general population (standardized mortality ratio, 1.34; 95% CI, 1.003-1.76; P = .03). Higher mortality was associated with age (hazard ratio per decade, 2.2; 95% CI, 1.7-2.7), impaired fasting glucose (hazard ratio, 2.6; 95% CI, 1.3-5.2), and cirrhosis (hazard ratio, 3.1, 95% CI, 1.2-7.8). Liver disease was the third leading cause of death (as compared with the thirteenth leading cause of death in the general Minnesota population), occurring in 7 (1.7%) subjects. Twenty-one (5%) patients were diagnosed with cirrhosis, and 13 (3.1%) developed liver-related complications, including 1 requiring transplantation and 2 developing hepatocellular carcinoma. CONCLUSIONS: Mortality among community-diagnosed NAFLD patients is higher than the general population and is associated with older age, impaired fasting glucose, and cirrhosis. Liver-related death is a leading cause of mortality, although the absolute risk is low.     

The role of physical activity in the management of impaired glucose tolerance: a systematic review

Although physical activity is widely reported to reduce the risk of type 2 diabetes in individuals with prediabetes, few studies have examined this issue independently of other lifestyle modifications. The aim of this review is to conduct a systematic review of controlled trials to determine the independent effect of exercise on glucose levels and risk of type 2 diabetes in people with prediabetes (IGT and/or IFG). A detailed search of MEDLINE (1966–2006) and EMBASE (1980–2006) found 279 potentially relevant studies, eight of which met the inclusion criteria for this review. All eight studies were controlled trials in individuals with impaired glucose tolerance. Seven studies used a multi-component lifestyle intervention that included exercise, diet and weight loss goals and one used a structured exercise training intervention. Four studies used the incidence of diabetes over the course of the study as an outcome variable and four relied on 2-h plasma glucose as an outcome measure. In the four studies that measured the incidence of diabetes as an outcome, the risk of diabetes was reduced by approximately 50% (range 42–63%); as these studies reported only small changes in physical activity levels, the reduced risk of diabetes is likely to be attributable to factors other than physical activity. In the remaining four studies, only one reported significant improvements in 2-h plasma glucose even though all but one reported small to moderate increases in maximal oxygen uptake. These results indicate that the contribution of physical activity independent of dietary or weight loss changes to the prevention of type 2 diabetes in people with prediabetes is equivocal.