Absence of gamma-range corticomuscular coherence during dynamic force in a deafferented patient

Recently, we studied corticomuscular coherence (CMC) in a visuomotor task and showed for the first time gamma-range (30–45 Hz) CMC during isometric compensation of a periodically modulated dynamic force. We speculated that for the control of such forces, the sensorimotor system resonates at gamma-range frequencies to rapidly integrate the visual and proprioceptive information and produce the appropriate motor command. In this study, we tested the role of the proprioceptive afferent feedback on gamma-range CMC by comparing the deafferented patient GL to six age- and sex-matched subjects during the performance of a visuomotor force task consisting of isometric compensation of static and dynamic forces applied on the finger. Patient GL presented no significant gamma-band CMC during dynamic force. Instead, she had only beta-range CMC as in the static force condition; concurrently, her performance was significantly worse than that of the controls in both conditions. This gives support to the conclusions of our previous paper and suggests that proprioceptive information is mandatory in the genesis of gamma-band CMC during the generation and control of dynamic forces.     

Arsenic and urinary bladder cell proliferation

Epidemiologic studies have demonstrated that a close association exists between the elevated levels of arsenic in drinking water and the incidence of certain cancers, including transitional cell carcinomas of the urinary bladder. We have employed in vitro and in vivo models to examine the effects of sodium arsenite on the urinary bladder epithelium. Mice exposed to 0.01% sodium arsenite in drinking water demonstrated hyperproliferation of the bladder uroepithelium within 4 weeks after initiating treatment. This occurred in the absence of amorphous precipitates and was accompanied by the accumulation of trivalent arsenite (iAs(3+)), and to a lesser extent dimethylarsenic (DMA), arsenate (iAs(5+)), and monomethylarsenic (MMA) in bladder tissue. In contrast to the bladder, urinary secretion was primarily in the form of DMA and MMA. Arsenic-induced cell proliferation in the bladder epithelium was correlated with activation of the MAP kinase pathway, leading to extracellular signal-regulated kinase (ERK) kinase activity, AP-1 activation, and expression of AP-1-associated genes involved in cell proliferation. Activation of the MAP kinase pathway involved both epidermal growth factor (EGF) receptor-dependent and -independent events, the latter involving Src activation. Studies summarized in this review suggest that arsenic accumulates in urinary bladder epithelium causing activation of specific signaling pathways that lead to chronic increased cell proliferation. This may play a non-epigenetic role in carcinogenesis by increasing the proliferation of initiated cells or increasing the mutational rate.     

The size of corpus callosum and functional connectivities of cortical regions in finger and shoulder movements

The correlations between the size of corpus callosum and the inter- and intra-hemispheric EEG coherence and the spatial EEG synchronization during finger and shoulder movements were analyzed in nine right-handed men. The cross-sectional surface areas of corpus callosum (CC) and of seven callosal regions were measured from the mid-sagittal slice of the anatomical MRI. Movement-related coherence between pairs of EEG electrodes overlying the central and parietal regions of both hemispheres was computed after spatially filtering EEG data by the Laplacian operator method. The spatial EEG synchronization was evaluated using omega-complexity, a novel measure which quantifies the number of independent sources of spontaneous EEG oscillations. The amplitude of coherence between the left and right S1/M1 areas after movement onset in the lower alpha band (7.8-9.8 Hz) correlated with the size of the callosal body in both types of movement. The size of the callosal body also correlated with the C3-Cz coherence in the 15.6-19.5 Hz band in finger movement, and in the 15.6-23.5 Hz band in shoulder movements. The size of the rostral, anterior intermediate and posterior intermediate truncus of CC correlated with omega-complexity in both types of movements indicating more foci of synchronized EEG oscillations in subjects with a large callosal truncus. The results suggest that the size of callosal truncus which is known to connect the primary sensorimotor and the supplementary motor areas of both hemispheres contributes to the coupling of EEG oscillations during voluntary finger and shoulder movements.     

Association of tumor necrosis factor-alpha and interleukin-1 gene polymorphisms with silicosis

Silicosis, an interstitial lung disease prevalent among miners, sand blasters, and quarry workers, is manifested as a chronic inflammatory response leading to severe pulmonary fibrotic changes. Proinflammatory cytokines, such as TNFalpha and IL-1, produced in the lung by type II epithelial cells and alveolar macrophages, have been strongly implicated in the formation of these lesions. Recently, a number of single nucleotide polymorphisms (SNPs), which quantitatively affect mRNA synthesis, have been identified in the TNFalpha promoter and IL-1 gene cluster and their frequency is associated with certain chronic inflammatory diseases. To assess the role of these SNPs in silicosis, we examined their frequency in 325 ex-miners with moderate and severe silicosis and 164 miners with no lung disease. The odds ratio of disease for carriers of the minor variant, TNFalpha (-238), was markedly higher for severe silicosis (4.0) and significantly lower for moderate silicosis (0.52). Regardless of disease severity, the odds ratios of disease for carriers of the IL-1RA (+2018) or TNFalpha (-308) variants were elevated. There were no significant consistent differences in the distribution of the IL-1alpha (+4845) or IL-1beta (+3953) variants with respect to disease status. In addition, several significant gene-gene and gene-gene-environment interactions were observed. Different associations between moderate cases and controls versus severe cases and controls were also observed in a number of these multigene comparisons. These studies suggest that gene-environment interactions involving cytokine polymorphisms play a significant role in silicosis by modifying the extent of and susceptibility to disease.     

Arsenic and atherosclerosis

Epidemiological studies have demonstrated a correlation between environmental or occupational arsenic exposure and a risk of vascular diseases related to atherosclerosis. Studies summarized in this review suggest that arsenic induces endothelial dysfunction, including inflammatory and coagulating activity as well as impairs nitric oxide (NO) balance. This may provide the pathophysiological basis for atherogenic potential of arsenic. Consistent with these data, arsenic accelerates atherosclerosis in apolipoprotein E (ApoE) deficient mice, a model of human atherosclerosis.     

Inhalation exposure of gas-metal arc stainless steel welding fume increased atherosclerotic lesions in apolipoprotein E knockout mice

Epidemiological studies suggest that welding, a process which generates an aerosol of inhalable gases and metal rich particulates, increases the risk for cardiovascular disease. In this study we analyzed systemic inflammation and atherosclerotic lesions following gas metal arc-stainless steel (GMA-SS) welding fume exposure. Apolipoprotein E knockout (apoE^−/−) mice, fed a Western diet, were exposed to GMA-SS at 40 mg/m³ for 3 h/day for ten days (∼8.26 μg daily alveolar deposition). Mice were sacrificed two weeks after exposure and serum chemistry, serum protein profiling and aortic lesion area were determined. There were no significant changes in serum total cholesterol, triglycerides or alanine aminotransferase. Serum levels of uric acid, a potent antioxidant, were decreased perhaps suggesting a reduced capacity to combat systemic oxidative stress. Inflammatory serum proteins interleukin 1 beta (IL-1β) and monocyte chemoattractant protein 3 (MCP-3) were increased two weeks after GMA-SS exposure. Analysis of atherosclerotic plaques showed an increase in lesion area as the result of GMA-SS exposure. In conclusion, GMA-SS exposure showed evidence of systemic inflammation and increased plaque progression in apoE^−/− mice. These results complement epidemiological and functional human studies that suggest welding may result in adverse cardiovascular effects.     

The prevalence of urinary incontinence and its influence on the quality of life in women from an urban Swedish population.

OBJECTIVES: To assess the prevalence of urinary incontinence and its influence on the quality of life. MATERIAL AND METHODS: A random sample of every fourth woman aged > or =20 years resident in a primary health care district of the city of G?teborg was obtained from the population register (n=2911). The women were invited by letter to complete a questionnaire concerning urinary incontinence. The women were also requested to assess their quality of life using a visual analogue scale. RESULTS: The overall response rate was 77%. The prevalence of urinary incontinence increased (p<0.001) in a linear fashion from 3% in the cohort 20-29 years to 32 % in the cohort of women aged > or =80 years. The proportion of women suffering from stress incontinence decreased (p<0.001) with increasing age, while the proportion of women suffering from urge and mixed incontinence increased (p<0.01) with increasing age. Women with stress incontinence had a greater body weight and had given birth to a greater number of children compared to continent women. There was, however, in this respect no difference between women with urge incontinence and continent women. Women with urinary incontinence reported a poorer quality of life compared to continent women (p<0.01). Women with urge incontinence and women with mixed incontinence reported a poorer quality of life compared to women with stress incontinence (p<0.05). Only 6% of the women from this population had sought medical attention for urinary incontinence. CONCLUSIONS: Although urinary incontinence was a prevalent condition, particularly among the elderly and had a negative influence on the quality of life, only a small number of women had sought medical care.     

The role of tumor necrosis factor-alpha in liver toxicity, inflammation, and fibrosis induced by carbon tetrachloride.

Hepatic expression of the proinflammatory cytokine tumor necrosis factor-alpha (TNFalpha) occurs in many acute and chronic liver diseases, as well as following exposure to hepatotoxic chemicals, and is believed to help influence both the damage and repair processes that occur following these insults by regulating additional mediators. We examined the role of TNFalpha in transgenic mice deficient in TNF receptors (TNFR) utilizing carbon tetrachloride (CCl(4)) as a model hepatotoxic agent that allowed for the evaluation of necrosis, inflammation, and fibrosis. Hepatocyte damage, as evident by local areas of liver necrosis and elevated levels of serum transaminase, occurred to a similar degree in wild-type and TNFR-deficient knockout (KO) mice following acute exposure to CCl(4). In contrast, the inflammatory response, manifested as an inflammatory cell influx, as well as induction of chemokines and adhesion molecules that occurred in wild-type mice following treatment with CCl(4), was not as evident in TNFR-KO mice. This response was associated primarily with type-1 (TNFR1) rather than type-2 (TNFR2) receptor responses. Liver fibrosis resulting from chronic CCl(4) exposure was also markedly dependent upon TNFalpha as demonstrated by almost a complete histological absence of fibrosis in TNFR-deficient mice. This was further supported by marked reductions in procollagen and transforming growth factor beta synthesis in TNFR-deficient mice. Taken together, these results indicate that TNFalpha is responsible for regulating products that induce inflammation and fibrosis but not direct hepatocyte damage in CCl(4)-induced hepatotoxicity.     

Intensity modulated radiosurgery of brain metastases with flattening filter-free beams

Purpose

Flattening filter free (FFF) irradiation potentially reduces treatment delivery time in radiosurgery thus eliminating intrafraction motion and increasing patient comfort. We compared plan quality and efficiency of VMAT and IMRT plans for FFF- and standard delivery for brain metastases with single fraction doses of 20 Gy and validated the dosimetric accuracy of the FFF delivery.

Material and Methods

CT data of 15 patients with brain metastases were included in this study. For every patient, 2 IMRT- and 2 VMAT-plans were created using a high-resolution MLC with two different delivery modes (6 MV standard vs. 6 MV FFF). Plan quality and efficiency was assessed by analysis of conformity, homogeneity, dose gradients, treatment delivery time and number of monitor units (MU). Dosimetric evaluation was performed for 10 FFF plans with radiochromic film and ion chamber.

Results

Plan quality was similar for both approaches. FFF provided a mean treatment time reduction of 51.5% with similar MU for VMAT and IMRT for this low-modulation paradigm. The dosimetric validations showed an absolute dose deviation of +0.93 ± 0.99% and γ-index analysis (3%/3 mm and 3%/1 mm) resulted in agreement of 99.08 ± 1.58% respectively 93.46 ± 2.41%.

Conclusion

FFF radiosurgery is an efficient technique for intensity modulated hypofractionated or single fraction treatments with similar plan quality when compared to flattened beams at reduced treatment time.