Even though the prognosis of LC from NSCLC is poor, small subsets of these patients survive longer. Our results suggest that more active treatment strategies including ITC, WBRT, and EGFR-TKI use might improve clinical outcomes in NSCLC patients with LC and good performance status, low initial CSF protein and WBC counts.

Objective To estimate the effects of a relatively protruded head and neck posture on postural balance, in computer based worker. Method Thirty participants, who work with computers for over 6 hrs per day (Group I), and thirty participants, who rarely work with computers (Group II), were enrolled. The head and neck posture was measured by estimating angles A and B. A being the angle between the tragus of the ear, the lateral canthus of the eye, and horizontal line and B the angle between the C7 spinous process, the tragus of the ear, and the horizontal line. The severity of head protrusion with neck extension was assessed by the subtraction of angle A from angle B. We also measured the center of gravity (COG) and postural balance by using computerized dynamic posturography to determine the effect of computer-based work on postural balance. Results Results indicated that group I had a relatively more protruded head with extensive neck posture (angle B-A of group I and group II, 28.2±8.3, 32.9±6.0; p<.05). The COG of group I tended more toward the anterior than that of group II. Postural imbalance and impaired ability to regulate movement in forward and backward direction were also found. Conclusion The results of this study suggest that forward head postures during computer-based work may contribute to some disturbance in the balance of healthy adults. These results could be applied to education programs regarding correct postures when working at a computer for extended periods of time.

MTV, a volumetric parameter of (18)F-FDG PET, is an important independent prognostic factor for survival and a better predictor of survival than SUVmax for the primary tumor in patients with esophageal carcinoma.

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Hutchinson-Gilford progeria syndrome (HGPS) is a rare autosomal dominant genetic disease that is caused by a silent mutation of the LMNA gene encoding lamins A and C (lamin A/C). The G608G mutation generates a more accessible splicing donor site than does WT and produces an alternatively spliced product of LMNA called progerin, which is also expressed in normal aged cells. In this study, we determined that progerin binds directly to lamin A/C and induces profound nuclear aberrations. Given this observation, we performed a random screening of a chemical library and identified 3 compounds (JH1, JH4, and JH13) that efficiently block progerin-lamin A/C binding. These 3 chemicals, particularly JH4, alleviated nuclear deformation and reversed senescence markers characteristic of HGPS cells, including growth arrest and senescence-associated β-gal (SA-β-gal) activity. We then used microarray-based analysis to demonstrate that JH4 is able to rescue defects of cell-cycle progression in both HGPS and aged cells. Furthermore, administration of JH4 to LmnaG609G/G609G-mutant mice, which phenocopy human HGPS, resulted in a marked improvement of several progeria phenotypes and an extended lifespan. Together, these findings indicate that specific inhibitors with the ability to block pathological progerin-lamin A/C binding may represent a promising strategy for improving lifespan and health in both HGPS and normal aging.

Targeted protein degradation allows targeting undruggable proteins for therapeutic applications as well as eliminating proteins of interest for research purposes. While several degraders that harness the proteasome or the lysosome have been developed, a technology that simultaneously degrades targets and accelerates cellular autophagic flux is still missing. In this study, we develop a general chemical tool and platform technology termed AUTOphagy-TArgeting Chimera (AUTOTAC), which employs bifunctional molecules composed of target-binding ligands linked to autophagy-targeting ligands. AUTOTACs bind the ZZ domain of the otherwise dormant autophagy receptor p62/Sequestosome-1/SQSTM1, which is activated into oligomeric bodies in complex with targets for their sequestration and degradation. We use AUTOTACs to degrade various oncoproteins and degradation-resistant aggregates in neurodegeneration at nanomolar DC50 values in vitro and in vivo. AUTOTAC provides a platform for selective proteolysis in basic research and drug development.

Vascular 18 F-FDG uptake marker represents inflammation in atherosclerotic lesions, but whether inflammation can be reversed by risk-modifying interventions has not, to our knowledge, been demonstrated. In this study, we evaluated the change of vascular 18 F-FDG uptake in response to lifestyle intervention on serial PET/CT scans and further assessed how the findings relate to atherogenic risk reduction. Methods: A total of 60 healthy adults underwent 18 F-FDG PET/CT scans and atherogenic riskfactor assessment at baseline and again after 17.1 6 8.3 mo of practicing lifestyle modification. The PET/CT images were evaluated for the presence of vascular 18 F-FDG lesions, and vesselto-blood-pool 18 F-FDG ratios were measured. Indices from summed ratios of positive lesions were compared and correlated to atherogenic risk factors. Results: At follow-up, significant reductions in diastolic blood pressure (P , 0.05), total cholesterol (P , 0.05), and low-density lipoprotein level (P , 0.05) and an increase in high-density lipoprotein (HDL) level (P , 0.0001) were demonstrated. On the initial PET/CT scan, 50 of 60 subjects showed 1 or more 18 F-FDG-positive lesions (5.9 6 5.0/subject), leading to a total of 352 vascular sites. On follow-up, 18 F-FDGpositive lesions were significantly reduced to 2.1 6 2.2 sites per subject (P , 0.0001) and a total of 124 sites (64.8% reduction). Follow-up 18 F-FDG-positive rates were significantly reduced for the aorta and iliac arteries. In addition, significant reductions in the whole-body 18 F-FDG index from 1.39 6 1.23 to 0.53 6 0.59 (P , 0.0001) and carotid 18 F-FDG index from 0.08 6 0.16 to 0.03 6 0.06 (P 5 0.01) were shown. The wholebody 18 F-FDG index correlated with total cholesterol (P , 0.05) and HDL level (P , 0.05), and the magnitude of reduction in the 18 F-FDG index closely correlated to the amount of increase in plasma HDL level (P 5 0.005). Conclusion: Our study demonstrated that vascular 18 F-FDG uptake is reversed in response to atherogenic risk reduction by lifestyle intervention and that the magnitude of improvement correlates to increases in plasma HDL levels. Thus, serial 18 F-FDG PET/CT may be useful for monitoring improvements in the inflammatory component of atherosclerotic lesions in response to risk modification.