Citations

Abstract Elevated intraocular pressure (IOP) is the most prevalent risk factor for glaucoma. All treatments, whether surgical or pharmaceutical, are aimed at lowering IOP. Prostaglandin analogues are a first line therapy for glaucoma due to their ability to reduce IOP, once-daily dosing, efficacy, and minimal side-effect profile. Whereas prostaglandin analogues have been known to alter aqueous humor outflow through the unconventional (uveoscleral) pathway, more recent evidence suggests their action also occurs through the conventional (trabecular) pathway. Understanding how prostaglandin analogues successfully lower IOP is important, as this information may lead to the discovery of new molecular targets for future therapeutic intervention. This review explores the current understanding of prostaglandin analogue biology as it pertains to IOP reduction and improved aqueous humor outflow facility.

Abstract This study examined habitat variables associated with 53 active bald eagle Haliaeetus leucocephalus nest sites in the Winona District of the Upper Mississippi River National Wildlife and Fish Refuge, Minnesota and Wisconsin. The Refuge is the most heavily visited refuge in the United States, where breeding eagle populations have been increasing dramatically. During February–April 2009, nest trees were identified and measured, nest heights were determined, distances to nearest water bodies were assessed, and forest inventories were conducted for the standing timber surrounding the nest trees. Nest densities and spacing were assessed within each navigation pool, and land cover types were examined within 100- and 1,000-m radii around known eagle nest sites and random points within the Refuge. Ninety-three percent of nest sites had supercanopy eastern cottonwoods Populus deltoides and silver maples Acer saccharinum as the nest trees. Potential human disturbances from highways, railroads, and commercial barge and recreational boat traffic were present within 400 m of 90% of known nest sites. Eagle nest sites were located an average of 1.52 km from the next nearest nest, with nest densities ranging from 0.32 to 9.72 nests/100 km2 among the four navigation pools of the Winona District. Land cover types around known nest sites and random points differed significantly at both 100- and 1,000 m scales, with wet forest and open water significantly more abundant and agricultural and developed lands significantly less abundant than around randomly selected points. Successful nests that fledged at least one young were spaced significantly further away from other active nests and were located in areas with lower tree density than were unsuccessful nests. Floodplain-nesting bald eagles tended to select the tallest, dominant trees for nest sites, placing nests near the height of the surrounding canopy. Human presence within the Refuge does not appear to be limiting the expansion of nesting bald eagles in this riverine habitat.

One commonly reported complication of pyrolytic carbon arthroplasty at the proximal interphalangeal (PIP) joint is an annoying, painless, squeaking postoperatively. This squeak has been anecdotally associated with implant loosening or impending dislocation. The purpose of this study was to investigate the etiology of this squeaking. Proximal and distal components of the pyrolytic carbon PIP implant were inserted into foam bones and mounted onto an oscillating test device. We evaluated the effect of 96 combinations of load, velocity, contact angle, implant size, lubrication, and displacement amplitude over a total of 300 cycles for each condition. Sound analysis was performed on squeaking conditions. Fourteen conditions resulted in squeaking, all with a sound pattern similar to that noted clinically. Unlubricated, “dry” joints did not squeak. Squeaking most commonly occurred with fetal bovine serum lubrication, at higher loads, and at 0 deg hyperextension. Hyaluronic acid viscosupplementation stopped the squeaking in all cases.

ABSTRACTHeparan sulfate proteoglycans (HSPGs) are key components of the extracellular matrix that mediate cell proliferation, invasion, and cellular signaling. The biological functions of HSPGs are linked to their co‐stimulatory effects on extracellular ligands (e.g., WNTs) and the resulting activation of transcription factors that control mammalian development but also associated with tumorigenesis. We examined the expression profile of HSPG core protein syndecans (SDC1–4) and glypicans (GPC1–6) along with the enzymes that initiate or modify their glycosaminoglycan chains in human breast cancer (HBC) epithelial cells. Gene expression in relation to cell proliferation was examined in the HBC cell lines MCF‐7 and MDA‐MB‐231 following treatment with the HS agonist heparin. Heparin increased gene expression of chain initiation and modification enzymes including EXT1 and NDST1, as well as core proteins SDC2 and GPC6. With HS/Wnt interactions established, we next investigated WNT pathway components and observed that increased proliferation of the more invasive MDA‐MB‐231 cells is associated with activation of the Wnt signaling pathway. Specifically, there was substantial upregulation (>5‐fold) of AXIN1, WNT4A, and MYC in MDA‐MB‐231 but not in MCF‐7 cells. The changes in gene expression observed for HSPG core proteins and related enzymes along with the associated Wnt signaling components suggest coordinated interactions. The influence of HSPGs on cellular proliferation and invasive potential of breast cancer epithelial cells are cell and niche specific. Further studies on the interactions between HSPGs and WNT ligands may yield clinically relevant molecular targets, as well as new biomarkers for characterization of breast cancer progression. J. Cell. Biochem. 115: 967–976, 2014. © 2013 Wiley Periodicals, Inc.

AbstractBackgroundRecent data suggest that acute coronary syndromes (ACS) and acute myocardial infarction (AMI) are characterized by an inflammatory subset of thrombosis. We have previously described the accumulation of neutrophils at the coronary culprit lesion site. In this work, we assessed the prognostic value of culprit site (CS) neutrophil accumulation on long‐term mortality in patients with AMI.Materials and methodsIn this prospective study, 417 AMI patients were enrolled after thrombectomy during primary percutaneous coronary intervention. The optimal cut‐off for CS neutrophil accumulation for predicting 4‐year all‐cause mortality was calculated using time‐dependent receiver operator characteristic curve analyses.ResultsThe median follow‐up time was 39 months interquartile range (IQR 21·4–54·6 months) corresponding to 1217 patient years of follow‐up. The cut‐off for CS neutrophil accumulation (difference between culprit neutrophil counts and systemic neutrophil counts) was 0·25 Giga/l. CS neutrophil accumulation occurred in 195 patients (47%) and was independently associated with mortality (hazard ratio 1·88 (95%CI 1·02–3·41, P = 0·043)). In patients with CS neutrophil accumulation, 1‐year mortality (10·8% vs. 7·2%) and 4‐year mortality (19·8% vs. 10·4%) were markedly increased compared with patients without local neutrophil accumulation. Concordance index for CS neutrophil accumulation and mortality was 0·64 (95% CI 0·51–0·77; P = 0·035). Patients with CS neutrophil accumulation had significantly more often nonobstructive lesions compared with patients without neutrophil accumulation (32·6% vs. 22·4%; P = 0·024).Conclusions Neutrophil accumulation at the coronary culprit lesion site is a strong and independent predictor of mortality in patients with ACS/AMI.

Background: The expertise required for proper electroencephalography (EEG) setup can make the 10-20 array unwieldy in the hospital setting. There may be a role for an EEG array with reduced leads to improve the efficiency of inpatient practice. Methods: Clips from 100 EEG records, 50 ictal and 50 non-ictal, in adult inpatients from January 1, 2007, to January 1, 2012, were retrospectively reviewed and selected for digital lead reduction and blind review. Two epileptologists reviewed these tracings and documented the presence of seizures and severe disturbance of background. The reduced array included 7 leads spanning the scalp. Three different montages were available. Sensitivity and specificity of the reduced array were calculated using the formal EEG report as the comparison standard. Results: For the detection of any seizure, the reduced array EEG had a sensitivity of 70% and specificity of 96%. Sensitivity for identifying encephalopathic patterns was 62% and specificity was 86%. Focal seizures were more readily identified by the reduced array (20 of 25) than were generalized ictal patterns (13 of 25). Conclusion: The reduced electrode array was insufficiently sensitive to seizure detection. Reducing EEG leads might not be a preferred means of optimizing hospital EEG efficiency.