Age and gender interactions on verbal memory performance.

Age and gender effects on verbal episodic memory are well established. However, the possibility of interactions between age and gender has been raised by studies linking estrogen and verbal memory performance, and by research suggesting gender differences in age-related cortical atrophy. We evaluated whether age by gender interactions in verbal memory were present. Subjects within three years of the median age of menopause were excluded from a large cohort of normal subjects, resulting in a younger sample (16-47 years) of 288 men and 285 women, and an older sample (55-89 years) of 201 men and 245 women. All subjects were administered the CVLT-2, a multiple-trial list-learning task. Verbal memory was negatively correlated with age for younger men, older men, and older women, but not for younger women. Multivariate analyses indicated age by gender interactions on memory for the younger group but not the older group. Results indicate that verbal memory declines with age for younger men but not younger women, whereas both older men and older women show age-related declines. These findings are consistent with hypotheses linking estrogen and verbal memory performance, and with imaging data suggesting that age-related hippocampal atrophy is found in younger men but not younger women. The role of estrogen on cognition in normal aging warrants further study.     

Visuospatial dysfunction following unilateral brain damage: dissociations in hierarchical and hemispatial analysis

Unlike the aphasias, visuospatial dysfunction has resisted fractionation into meaningful spared and impaired component functions. In this study, we show that unilateral brain damage results in pronounced dissociations in both hierarchical and hemispatial processing. Patients with left-hemisphere damage showed the greatest impairment in drawing forms at the lower level of hierarchical stimuli presented in right hemispace, whereas patients with right-hemisphere compromise displayed the opposite pattern. We discuss implications of these results for research in visuospatial function and clinical assessment of visuospatial dysfunction.     

Age effects on executive ability

Heterogeneity of executive tasks has made it difficult to determine whether there are age-related declines in executive functioning. To address this issue, 112 individuals, 20-79 years old, took the California Trail Making Test (CTMT) and the California Stroop Test (CST), subtests of the Delis-Kaplan Executive Function Scale (D. C. Delis, E. Kaplan, & J. H. Kramer, in press) that include measurement of component skills embedded in the executive function tasks. Multiple regression analyses revealed that after controlling for component skills, age had a significant effect on the executive requirement of the CST, namely speed on the interference condition. Age did not affect switching performance on the letter-number condition of the CTMT. Additional analyses revealed that age was significantly associated with commission of certain types of errors. This study confirms the importance of partialing out components in the assessment of multidimensional cognitive tasks, particularly when making age comparisons. It also emphasizes specificity over generalizability when examining the impact of age on cognition.     

Dopamine receptor and transporter levels are altered in the brain of Purkinje Cell Degeneration mutant mice

The Purkinje Cell Degeneration (Nna1pcd, pcd) mutant mouse is mainly characterized by the complete, primary loss of the Purkinje cells and the secondary, partial, retrograde loss of the granule and inferior olive neurons and is considered a model of human degenerative ataxia. We determined, by in vitro quantitative autoradiography and in situ hybridization, the effects of the Purkinje cell deprivation on the dopaminergic system of the Nna1pcd mutant mouse. The dopamine transporters, as determined by [3H]WIN35428 binding, were increased compared with wild-type mice in the ventral mesencephalic dopaminergic nuclei and in the lateral striatum, motor cortex and septum. In the cerebellum of Nna1pcd mice, the dopamine transporters showed a significant increase in the deep cerebellar nuclei, but were significantly decreased in the molecular layer. The D1-like receptors, as determined by [3H]SCH23390 binding, increased significantly in the Nna1pcd substantia nigra. The D2/D3 receptors, as determined by [3H]raclopride binding, exhibited a significant decrease in lateral divisions of the striatum. Significant increases in D2-like receptors, as determined by [3H]nemonapride binding, were observed in most divisions of the striatum as well as in septum, hippocampus, and piriform cortex. This D2-like fraction most probably corresponds to the D4 receptor subtype. In the cerebellum of Nna1pcd mice, D2-like receptors were significantly decreased in the molecular layer. The results suggest an increased excitatory input on the dopaminergic mesencephalic neurons and an alteration of the dopaminergic neurotransmission in basal ganglia, cortical and limbic regions of the Nna1pcd mutant mouse. In the cerebellum, the significant downregulation of the dopamine transporters and D2-like receptors in the mutant cerebellar molecular layer is possibly due to the absence of the Purkinje cells.     

Endotoxemia during supraceliac aortic crossclamping is associated with suppression of the monocyte CD14 mechanism: possible role of transforming growth factor-beta1

PURPOSE: Monocyte CD14 and its soluble form (sCD14) mediate the proinflammatory response to endotoxemia. The aim of this study was to measure the changes to these factors after major aortic surgery and the possible inhibitory role of transforming growth factor-beta(1) (TGF-beta(1)) during these procedures. METHODS: Twenty-four patients with supraceliac aortic crossclamping during thoracoabdominal aortic aneurysm (TAAA) repair and 12 patients with infrarenal aortic crossclamping as part of infrarenal aneurysm repair (AAA) were studied. Blood was collected at incision, aortic clamping, and reperfusion and at 1, 8, and 24 hours after reperfusion. Samples were assayed for endotoxin, peripheral blood monocyte CD14 expression, sCD14, tumor necrosis factor-alpha, and TGF-beta(1). RESULTS: Although there was significant endotoxemia on reperfusion in both groups of patients, peak plasma endotoxin levels were significantly higher in patients with TAAA (P =.001). Monocyte CD14 and plasma sCD14 were significantly decreased in patients with TAAA at reperfusion and 1 hour after reperfusion (P <.01, both points). In patients with AAA, a significant upregulation of CD14 was observed at 24 hours after reperfusion (P <.01), but no significant changes in sCD14 were observed. TNF-alpha showed no significant changes during the study period in both groups. In patients with TAAA, TGF-beta(1) showed significant elevation at all time points (P <.01); whereas in patients with AAA, TGF-beta(1) showed no significant changes. CONCLUSION: Splanchnic ischemia reperfusion in patients who undergo supraceliac aortic clamping is associated with peripheral blood monocyte CD14 suppression and significant elevation of TGF-beta(1). TGF-beta(1) may play an important role in modulating the immune response to endotoxemia during major aortic aneurysm surgery.     

Fatal meningoencephalitis due to Bacillus anthracis

Abstract: We report the first case of fatal anthrax meningoencephalitis in Hong Kong over the past 60 years. A 13 year-old boy presented with right lower quadrant pain, diarrhoea and progressive headache. Lumbar puncture yielded gram positive bacilli initially thought to be Bacillus cereus, a contaminant. He was treated with ampicillin and cefotaxime, but died 3 days after hospitalization. The organism isolated from blood and cerebrospinal fluid was later identified as Bacillus anthracis.     

A prospective study of methylenetetrahydrofolate reductase and methionine synthase gene polymorphisms, and risk of colorectal adenoma

We examined the relationship between a functional polymorphism (667C-- >T, ala-->val) of the methylenetetrahydrofolate reductase gene (MTHFR) and the risk of colorectal adenomas in the prospective Nurses' Health Study. Among 257 incident polyp cases and 713 controls, the MTHFR val/val polymorphism [relative risk (RR) = 1.35, 95% confidence interval (CI) 0.84-2.17] was not significantly associated with risk of adenomas. This lack of association was observed for both small (RR = 1.36, 95% CI 0.76-2.45) and large (RR = 1.32, 95% CI 0.66-2.66) adenomas. Furthermore, there was no significant interaction between this polymorphism and consumption of either folate, methionine or alcohol. We also examined the relationship of a newly identified polymorphism (asp919gly) of the methionine synthase gene (MS) with the risk of colorectal adenomas in the same population. The MS gly/gly polymorphism was also not significantly associated with risk of colorectal adenomas (RR = 0.66, 95% CI 0.26-1.70). These results, which need to be confirmed in other studies, suggest that the MTHFR val/val polymorphism, which has been previously inversely associated with risk of colorectal cancer, plays a role only in a late stage (adenoma-- >carcinoma) of colorectal tumorigenesis, and/or may protect against malignant transformation in the subset of benign adenomas, which may progress to malignancy.      

Attentional Dysfunction Associated with Posttraumatic Stress Disorder Among Rape Survivors

Posttraumatic stress disorder (PTSD) is characterized by subjective reports of decreased concentration and an inability to sustain attention. Some empirical validation of these symptoms has been demonstrated via reduced performance on attentional tests among war veterans with PTSD. However, the significance of such findings is unclear given high co-morbidity with other psychiatric, neurologic, and substance abuse disorders among veterans. The present study examined neuropsychological functioning among rape survivors with PTSD, a patient population with comparatively low rates of psychiatric co-morbidity. Rape survivors with PTSD (PTSD+; n = 15) were compared to rape survivors without PTSD (PTSD–; n = 16) and age- and education-matched nontraumatized controls (CTRL; n = 16) on tests of attention. Performance of the PTSD+ group was significantly worse than the other groups on measures of sustained and divided attention, but not on shifting of visuospatial selective attention. Performance differences were not attributable to co-morbid psychiatric disorders or substance abuse. The implications of these findings regarding the effects of trauma on attentional functions are discussed.     

Does prenylation predict progression in NAFLD?

Non-alcoholic fatty liver disease (NAFLD) often develops in concert with related metabolic diseases, such as obesity, dyslipidemia and insulin resistance. Prolonged lipid accumulation and inflammation can progress to non-alcoholic steatohepatitis (NASH). Although factors associated with the development of NAFLD are known, triggers for the progression of NAFLD to NASH are poorly understood. Recent findings published in The Journal of Pathology reveal the possible regulation of NASH progression by metabolites of the mevalonate pathway. Mevalonate can be converted into the isoprenoids farnesyldiphosphate (FPP) and geranylgeranyl diphosphate (GGPP). GGPP synthase (GGPPS), the enzyme that converts FPP to GGPP, is dysregulated in humans and mice during NASH. Both FPP and GGPP can be conjugated to proteins through prenylation, modifying protein function and localization. Deletion or knockdown of GGPPS favors FPP prenylation (farnesylation) and augments the function of liver kinase B1, an upstream kinase of AMP-activated protein kinase (AMPK). Despite increased AMPK activation, livers in Ggpps-deficient mice on a high-fat diet poorly oxidize lipids due to mitochondrial dysfunction. Although work from Liu et al provides evidence as to the potential importance of the prenylation portion of the mevalonate pathway during NAFLD, future studies are necessary to fully grasp any therapeutic or diagnostic potential. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.