Standing Balance and Spatiotemporal Aspects of Gait Are Impaired Upon Nocturnal Awakening in Healthy Late Middle-Aged and Older Adults

Study Objectives: Nocturnal awakenings may constitute a unique risk for falls among older adults. We describe differences in gait and balance between presleep and midsleep testing, and whether changes in the lighting environment during the midsleep testing further affect gait and balance. Methods: Twenty-one healthy, late middle-aged and older (64.7 ± 8.0 y) adults participated in this repeated-measures design consisting of four overnight laboratory stays. Each night, participants completed baseline visual acuity, gait, and balance testing. After a 2-h sleep opportunity, they were awakened for 13 min into one of four lighting conditions: very dim white light (\u3c 0.5 lux); dim white light (∼28.0 lux); dim orange light (∼28.0 lux); and white room-level light (∼200 lux). During this awakening, participants completed the same sequence of testing as at baseline. Results: Low-contrast visual acuity significantly decreased with decreasing illuminance conditions (F(3,45) = 98.26, p \u3c 0.001). Our a priori hypothesis was confirmed in that variation in stride velocity and center of pressure path length were significantly worse during the mid-sleep awakening compared to presleep baseline. Lighting conditions during the awakening, however, did not influence these parameters. In exploratory analyses, we found that over one-third of the tested gait and balance parameters were significantly worse at the midsleep awakening as compared to baseline (p \u3c 0.05), and nearly one-quarter had medium to large effect sizes (Cohen d ≥ 0.5; r ≥ 0.3). Conclusions: Balance and gait are impaired during midsleep awakenings among healthy, late middle-aged and older adults. This impairment is not ameliorated by exposure to room lighting, when compared to dim lights

Simultaneous electrochemical detection of both PSMA (+) and PSMA (-) prostate cancer cells using an RNA/peptide dual-aptamer probe

Using an RNA/peptide dual-aptamer probe, both PSMA (+) and PSMA (-) prostate cancer cells were simultaneously detected by electrochemical impedance spectroscopy. This approach can be applied as a general tool for early diagnosis of prostate cancer.CATALONA WJ, 1993, JAMA-J AM MED ASSOC, V270, P948Lupold SE, 2002, CANCER RES, V62, P4029Kue PF, 2002, INT J CANCER, V102, P572, DOI 10.1002/ijc.10734Drummond TG, 2003, NAT BIOTECHNOL, V21, P1192, DOI 10.1038/nbt873DARAIN F, 2004, BIOSENS BIOELECTRON, V20, P856Ban CG, 2004, NUCLEIC ACIDS RES, V32, DOI 10.1093/nar/gnh109Ghosh A, 2004, J CELL BIOCHEM, V91, P528, DOI 10.1002/jcb.10661LEVIN MA, 2005, J UROLOGY, V159, P475Rodriguez MC, 2005, CHEM COMMUN, P4267, DOI 10.1039/b506571bZitzmann S, 2005, CLIN CANCER RES, V11, P139Horninger W, 2001, CANCER-AM CANCER SOC, V91, P1667Lang SH, 2001, BRIT J CANCER, V85, P590Yamamoto T, 2001, UROLOGY, V58, P994Palecek E, 2002, CRIT REV ANAL CHEM, V32, P261Narain V, 2002, CANCER METAST REV, V21, P17Edwards S, 2005, BRIT J CANCER, V92, P376, DOI 10.1038/sj.bjc.6602261Postma R, 2005, EUR J CANCER, V41, P825, DOI 10.1016/j.ejca.2004.12.029Cahova-Kucharikova K, 2005, ANAL CHEM, V77, P2920Rahman MA, 2005, ANAL CHEM, V77, P4854, DOI 10.1021/ac050558vCho M, 2006, NUCLEIC ACIDS RES, V34, DOI 10.1093/nar/gkl364Farokhzad OC, 2006, P NATL ACAD SCI USA, V103, P6315, DOI 10.1073/pnas.0601755103Chu TC, 2006, CANCER RES, V66, P5989, DOI 10.1158/0008-5472.CAN-05-4583McNamara JO, 2006, NAT BIOTECHNOL, V24, P1005, DOI 10.1038/nbt1223Palecek E, 1998, BIOSENS BIOELECTRON, V13, P621Min K, 2008, BIOSENS BIOELECTRON, V23, P1819, DOI 10.1016/j.bios.2008.02.021CHO M, 2008, BMB REPORTS, V41, P119Kim D, 2007, J AM CHEM SOC, V129, P7661, DOI 10.1021/ja071471pMaalouf R, 2007, ANAL CHEM, V79, P4879, DOI 10.1021/ac070085nKRAHN MD, 1994, JAMA-J AM MED ASSOC, V272, P773

Sinus Histiocytosis with Massive Lymphadenopathy: A Case Report with Pleural Effusion and Cervical Lymphadenopathy

Sinus histiocytosis with massive lymphadenopathy (SHML) is a rare disorder characterized by a nonneoplastic proliferation of distinctive histiocyte cells within lymph node sinuses and lymphatics in extranodal sites. SHML occurs worldwide and is primarily a disease of childhood and early adulthood. A 26-yr-old man presented with painless palpable lymph node in cervical area. Radiographic studies revealed pleural effusion with lymphadenopathy and calcification in mediastinum. The cervical lymph node biopsy showed dilated sinuses filled with histiocytes with clear cytoplasm. The cells stained positive with CD68 and S-100. These cytologic and immunohistochemical findings were considered consistent with the diagnosis of SHML

Robust lithium-ion anodes based on nanocomposites of iron oxide-carbon-silicate

Robust composite particles containing Fe3O4 cores and porous conductive carbon-silicate layers were synthesized using an aerosol-assisted process followed by vapor coating using organosilanol as the precursor. Such unique synthesis enables the composites with high capacity and good cycle performance, and can be extended towards other oxide composites for energy storage.close5

The Role of TNF-α in Mice with Type 1- and 2- Diabetes

Background: Previously, we have demonstrated that short-term treatment of new onset diabetic Non-obese diabetic (NOD) mice, mice that are afflicted with both type 1 (T1D) and type 2 (T2D) diabetes with either Power Mix (PM) regimen or alpha1 antitrypsin (AAT) permanently restores euglycemia, immune tolerance to self-islets and normal insulin signaling. Methodology and Principal Findings: To search for relevant therapeutic targets, we have applied genome wide transcriptional profiling and systems biology oriented bioinformatics analysis to examine the impact of the PM and AAT regimens upon pancreatic lymph node (PLN) and fat, a crucial tissue for insulin dependent glucose disposal, in new onset diabetic non-obese diabetic (NOD) mice. Systems biology analysis identified tumor necrosis factor alpha (TNF-$\alpha$) as the top focus gene hub, as determined by the highest degree of connectivity, in both tissues. In PLNs and fat, TNF-$\alpha$ interacted with 53% and 32% of genes, respectively, associated with reversal of diabetes by previous treatments and was thereby selected as a therapeutic target. Short-term anti-TNF-$\alpha$ treatment ablated a T cell-rich islet-invasive and beta cell-destructive process, thereby enhancing beta cell viability. Indeed anti-TNF-$\alpha$ treatment induces immune tolerance selective to syngeneic beta cells. In addition to these curative effects on T1D anti-TNF-e33254 treatment restored in vivo insulin signaling resulting in restoration of insulin sensitivity. Conclusions: In short, our molecular analysis suggested that PM and AAT both may act in part by quenching a detrimental TNF-$\alpha$ dependent effect in both fat and PLNs. Indeed, short-term anti-TNF-$\alpha$ mAb treatment restored enduring euglycemia, self-tolerance, and normal insulin signaling

Genetic Ablation of Bcl-x Attenuates Invasiveness without Affecting Apoptosis or Tumor Growth in a Mouse Model of Pancreatic Neuroendocrine Cancer

Tumor cell death is modulated by an intrinsic cell death pathway controlled by the pro- and anti-apoptotic members of the Bcl-2 family. Up-regulation of anti-apoptotic Bcl-2 family members has been shown to suppress cell death in pre-clinical models of human cancer and is implicated in human tumor progression. Previous gain-of-function studies in the RIP1-Tag2 model of pancreatic islet carcinogenesis, involving uniform or focal/temporal over-expression of Bcl-xL, demonstrated accelerated tumor formation and growth. To specifically assess the role of endogenous Bcl-x in regulating apoptosis and tumor progression in this model, we engineered a pancreatic β-cell-specific knockout of both alleles of Bcl-x using the Cre-LoxP system of homologous recombination. Surprisingly, there was no appreciable effect on tumor cell apoptosis rates or on tumor growth in the Bcl-x knockout mice. Other anti-apoptotic Bcl-2 family members were expressed but not substantively altered at the mRNA level in the Bcl-x-null tumors, suggestive of redundancy without compensatory transcriptional up-regulation. Interestingly, the incidence of invasive carcinomas was reduced, and tumor cells lacking Bcl-x were impaired in invasion in a two-chamber trans-well assay under conditions mimicking hypoxia. Thus, while the function of Bcl-x in suppressing apoptosis and thereby promoting tumor growth is evidently redundant, genetic ablation implicates Bcl-x in selectively facilitating invasion, consistent with a recent report documenting a pro-invasive capability of Bcl-xL upon exogenous over-expression

Loss of DPP4 activity is related to a prothrombogenic status of endothelial cells: implications for the coronary microvasculature of myocardial infarction patients

Pro-coagulant and pro-inflammatory intramyocardial (micro)vasculature plays an important role in acute myocardial infarction (AMI). Currently, inhibition of serine protease dipeptidyl peptidase 4 (DPP4) receives a lot of interest as an anti-hyperglycemic therapy in type 2 diabetes patients. However, DPP4 also possesses anti-thrombotic properties and may behave as an immobilized anti-coagulant on endothelial cells. Here, we studied the expression and activity of endothelial DPP4 in human myocardial infarction in relation to a prothrombogenic endothelial phenotype. Using (immuno)histochemistry, DPP4 expression and activity were found on the endothelium of intramyocardial blood vessels in autopsied control hearts (n = 9). Within the infarction area of AMI patients (n = 73), this DPP4 expression and activity were significantly decreased, coinciding with an increase in Tissue Factor expression. In primary human umbilical vein endothelial cells (HUVECs), Western blot analysis and digital imaging fluorescence microscopy revealed that DPP4 expression was strongly decreased after metabolic inhibition, also coinciding with Tissue Factor upregulation. Interestingly, inhibition of DPP4 activity with diprotin A also enhanced the amount of Tissue Factor encountered and induced the adherence of platelets under flow conditions. Ischemia induces loss of coronary microvascular endothelial DPP4 expression and increased Tissue Factor expression in AMI as well as in vitro in HUVECs. Our data suggest that the loss of DPP4 activity affects the anti-thrombogenic nature of the endothelium

Effect of E. coli MutL on the steady-state ATPase activity of MutS in the presence of short blocked end DNAs

The effect of wild-type and mutant MULL on the steady-state ATPase activity of MutS from Escherichia coli has been investigated in the absence and presence of 22, 50, and 75 base pair hetero- and homoduplex DNAs with open and blocked ends. The steady-state ATPase activity of MutS has been measured at 37 degrees C using a spectrophotometric method. The presence Of MutL did not affect appreciably on the ATPase activity of MutS in the absence of DNA or in the presence of blocked end homoduplex DNAs. However, the addition of MULL affected oppositely on the ATPase activity of MutS in the presence of G-T mismatched DNAs depending on their end status. We have also found that only the ATPase active forms of MutL increased the ATPase activity of MutS in the presence of G-T mismatched DNAs with blocked ends. The results suggest that MutL ATPase activity is required to catalyze dissociation of the MutS sliding clamps. (C) 2009 Elsevier Inc. All rights reserved.X112sciescopu

Steady-state ATPase activity of E-coli MutS modulated by its dissociation from heteroduplex DNA

The ability of MutS to recognize mismatched DNA is required to initiate a mismatch repair (MMR) system. ATP binding and hydrolysis are essential in this process, but their role in MMR is still not fully understood. In this study, steady-state ATPase activities of MutS from Escherichia coli were investigated using the spectrophotometric method with a double end-blocked heteroduplex containing gapped bases. The ATPase activities of MutS increased as the number of gapped bases increased in a double end-blocked heteroduplex with 2-8 gapped bases in the chain, indicating that MutS dissociates from DNA when it reaches a scission during movement along the DNA. Since movement of MutS along the chain does not require extensive ATP hydrolysis and the ATPase activity is only enhanced when MutS dissociates from a heteroduplex, these results support the sliding clamp model in which ATP binding by MutS induces the formation of a hydrolysis-independent sliding clamp. (C) 2007 Elsevier Inc. All rights reserved.X11sciescopu