Comparison of first, second, and third versus the average of six probe-corneal touches for intraocular measurement of two rebound tonometers in healthy horses.

The aim of this study was to evaluate the intraocular pressure (IOP) measurements obtained from first, second, and third probe-cornea touch (PCT) and compare them with the average of six PCTs using two rebound tonometers in horses. This study enrolled a total of thirty-eight stallions, comprising of 24 Arabian horses and 14 cross-breeds (with an average age of 8 ± 3 years). The IOP measurements of first, second, and third, as well as the average of six PCTs were obtained using either Tonovet (TV) or Tonovet Plus (TV+) rebound tonometers. The mean differences (95% limits of agreement) between the average of six PCTs and the first, second, and third PCTs were 0.1 (-4.8 to 5), 0.2 (-4.8 to 4.5), and 0.2 (-3.6 to 4.0) mmHg with TV, respectively. With TV+, the differences were 0.3 (-6.6 to 7.2), 1.1 (-8.6 to 10.8), and -0.2 (-3.6 to 4.0) mmHg, respectively. Compared to the average of six PCTs, only 89.5%, 92.1%, and 97.4% of IOP measurements obtained from TV and 78.9%, 73.3%, and 65.8% of IOP measurements obtained from TV+ were within 4 mmHg of the average of six PCTs for first, second, and third PCTs, respectively. In conclusion, the measurement of IOP in the first PCT achieved best agreement with the IOP measurement of six average PCTs. Therefore, the first PCT could be considered as an alternative option for measuring IOP in horses when obtaining an average of six PCTs is not feasible.

Long-duration immediate postoperative knee flexion positioning results in better functional outcomes after total knee arthroplasty.

OBJECTIVE: This study aimed to evaluate the effects of affected knee flexion for 24 vs. 72 hours on blood loss, pain, range of motion, and functional outcomes after total knee arthroplasty. PATIENTS AND METHODS: The present study included 46 participants with a mean age of 64.33 ± 6.70 years. The affected knee of the first 23 participants, based on the order of operations, was positioned at 70° flexion for 24 hours, and the knee of the next 23 participants was positioned at 70° flexion for 72 hours. Participants were evaluated before the operation and on postoperative day 3 and week 6. Pain, edema, range of motion, time up and go test scores, and Western Ontario McMaster Universities Arthritis Index scores, hemoglobin, and hematocrit were measured before the operation and on postoperative at day 3 and week 6. RESULTS: We found that the calculated blood loss was 575.07 ± 282.44 and 578.39 ± 297.11 mL in patients who underwent short- and long-duration flexion positioning, respectively (p = 0.921). The active flexion angles at postoperative week 6 were 83.61° ± 22.03° and 105.91° ± 13.06° in the short- and long-duration flexion groups, respectively (p < 0.01). Furthermore, the Western Ontario and McMaster Universities Arthritis Index scores at postoperative week 6 were 35.52 ± 24.71 and 17.17 ± 15.37 in the short- and long-duration flexion groups, respectively (p < 0.01). CONCLUSIONS: Long-duration flexion positioning after total knee arthroplasty may lead to better middle-term flexion range of motion and physical function scores than short-duration flexion positioning.

Long Term Follow-Up of Stereotactic Body Radiation Therapy for Refractory Ventricular Tachycardia in Advanced Heart Failure Patients.

Background: Initial studies of stereotactic body radiation therapy (SBRT) for refractory ventricular tachycardia (VT) have demonstrated impressive efficacy. Follow-up analyses have found mixed results and the role of SBRT for refractory VT remains unclear. We performed palliative, cardiac radio ablation in patients with ventricular tachycardia refractory to ablation and medical management. Methods: Arrhythmogenic regions were targeted by combining computed tomography imaging with electrophysiologic mapping with collaboration from a radiation oncologist, electrophysiologist and cardiac imaging specialist. Patients were treated with a single fraction 25 Gy. Total durations of VT, the quantity of antitachycardia pacing (ATP) and shocks before and after treatment as recorded by implantable cardioverter-defibrillators (ICDs) were analyzed. Follow-up extended until most recent device interrogation unless transplant, death or repeat ablation occurred sooner. Results: Fourteen patients (age 50-78, four females) were treated and had an average of two prior ablations. Nine had ACC/AHA Stage D heart failure and three had left ventricular assist devices (LVAD). Two patients died shortly after SBRT, one received a prompt heart transplant and another had significant VT durations in the following months that were inaccurately recorded by their device. Ten of the 14 patients remained with adequate data post SBRT for analysis with an average follow-up duration of 216 days. Seven of those 10 patients had a decrease in VT post SBRT. Comparing the 90 days before treatment to cumulative follow-up, patients had a 59% reduction in VT, 39% reduction in ATP and a 60% reduction in shocks. Four patients received repeat ablation following SBRT. Pneumonitis was the only complication, occurring in four of the fourteen patients. Conclusion: SBRT may have value in advanced heart failure patients with refractory VT acutely but the utility over long-term follow-up appears modest. Prospective randomized data is needed to better clarify the role of SBRT in managing refractory VT.

ETM-ANN approach application for thiobenzamide and quinolizidine derivatives.

The structure anti-influenza activity relationships of thiobenzamide and quinolizidine derivatives, being influenza fusion inhibitors, have been investigated using the electronic-topological method (ETM) and artificial neural network (ANN) method. Molecular fragments specific for active compounds and breaks of activity were calculated for influenza fusion inhibitors by applying the ETM. QSAR descriptors such as molecular weight, E(HOMO), E(LUMO), ΔE, chemical potential, softness, electrophilicity index, dipole moment, and so forth were calculated, and it was found to give good statistical qualities (classified correctly 92%, or 48 compounds from 52 in training set, and 69% or 9 compounds from 13 in the external test set). By using multiple linear regression, several QSAR models were performed with the help of calculated descriptors and the compounds activity data. Among the obtained QSAR models, statistically the most significant one is the one of skeleton 1 with R(2) = 0.999.

Organic matter and heavy metal removals from complexed metal plating effluent by the combined electrocoagulation/Fenton process.

In the present study, the treatment of metal plating wastewater containing complexed metals originating from the nickel and zinc plating process by electrocoagulation (EC) using stainless steel electrodes was explored. In order to improve the organic matter removal efficiency, the effect of H(2)O(2) addition to the electrocoagulation (the combined EC/Fenton process) application was investigated. For this purpose, a wide range of H(2)O(2) concentrations varying between 15 and 230 mM was tested. All EC and EC/Fenton processes were performed at an initial pH of 2.6 and at an optimized current density of 22 mA/cm(2). Although up to 30 mM H(2)O(2) addition improved the EC process performance in terms of organic matter abatement, the highest COD and TOC removal efficiencies were obtained for the combined EC/Fenton process in the presence of 20 mM H(2)O(2). Nickel and zinc were completely removed for all runs tested in the present study after pH adjustments. At the optimized operation conditions, the combined EC/Fenton process proved to be an alternative treatment method for the improvement of organic matter reduction as well as complexed metal removal from metal plating industry wastewater.

Probing the S1/S1' substrate binding pocket geometry of HIV-1 protease with modified aspartic acid analogues.

Aspartates 25 and 125, the active site residues of HIV-1 protease, participate functionally in proteolysis by what is believed to be a general acid-general base mechanism. However, the structural role that these residues may play in the formation and maintenance of the neighboring S1/S1' substrate binding pockets remains largely unstudied. Because the active site aspartic acids are essential for catalysis, alteration of these residues to any other naturally occurring amino acid by conventional site-directed mutagenesis renders the protease inactive, and hence impossible to characterize functionally. To investigate whether Asp-25 and Asp-125 may also play a structural role that influences substrate processing, a series of active site protease mutants has been produced in a cell-free protein synthesizing system via readthrough of mRNA nonsense (UAG) codons by chemically misacylated suppressor tRNAs. The suppressor tRNAs were activated with the unnatural aspartic acid analogues erythro-beta-methylaspartic acid, threo-beta-methylaspartic acid, or beta,beta-dimethylaspartic acid. On the basis of the specific activity measurements of the mutants that were produced, the introduction of the beta-methyl moiety was found to alter protease function to varying extents depending upon its orientation. While a beta-methyl group in the erythro orientation was the least deleterious to the specific activity of the protease, a beta-methyl group in the threo orientation, present in the modified proteins containing threo-beta-methylaspartate and beta,beta-dimethylaspartate, resulted in specific activities between 0 and 45% of that of the wild type depending upon the substrate and the substituted active site position. Titration studies of pH versus specific activity and inactivation studies, using an aspartyl protease specific suicide inhibitor, demonstrated that the mutant proteases maintained bell-shaped pH profiles, as well as suicide-inhibitor susceptibilities that are characteristic of aspartyl proteases. A molecular dynamics simulation of the beta-substituted aspartates in position 25 of HIV-1 protease indicated that the threo-beta-methyl moiety may partially obstruct the adjacent S1' binding pocket, and also cause reorganization within the pocket, especially with regard to residues Val-82 and Ile-84. This finding, in conjunction with the biochemical studies, suggests that the active site aspartate residues are in proximity to the S1/S1' binding pocket and may be spatially influenced by the residues presented in these pockets upon substrate binding. It thus seems possible that the catalytic residues cooperatively interact with the residues that constitute the S1/S1' binding pockets and can be repositioned during substrate binding to orient the active site carboxylates with respect to the scissile amide bond, a process that likely affects the facility of proteolysis.

Structurally altered substrates for DNA topoisomerase I. Effects of inclusion of a single 3'-deoxynucleotide within the scissile strand.

A partial DNA duplex containing a high efficiency topoisomerase I cleavage site was substituted singly at each of three sites with 3'-deoxyadenosine. Depending on the site of substitution, the facility of the topoisomerase I-mediated cleavage or ligation reactions was altered. Inclusion of the modified nucleoside at the 5'-end of the acceptor oligonucleotide diminished the rate of religation following substrate cleavage by the enzyme.

DNA duplexes containing 3'-deoxynucleotides as substrates for DNA topoisomerase I cleavage and ligation.

The DNA cleavage-ligation reaction of DNA topoisomerase I was investigated employing synthetic DNA substrates containing 3'-deoxyadenosine or 3'-deoxythymidine at specific sites and acceptor oligonucleotides of different lengths. The modified nucleotides were substituted systematically within the putative enzyme-binding domain and also next to the high efficiency cleavage site to determine the effect of single base changes on enzyme function. Depending on the site of substitution, the facility of the cleavage and ligation reactions were altered. The bases at positions -1 and -2 on the noncleaved strand were found to be important for determining the site of cleavage. Inclusion of 3'-deoxythymidine in the scissile strand at position -1 permitted the demonstration that topoisomerase I can cleave and form a 2' --> 5'-phosphodiester linkage. Partial duplexes doubly modified at positions -4 or -6 in the noncleaved strand and at positions +1 or -1 within scissile strand were not good substrates for topoisomerase I, showing that cleavage can depend importantly on binding interactions based on structural alterations at spatially separated sites. Substitution of a 3'-deoxynucleotide on the scissile strand at position -6 enhanced formation of the ligation product resulting from cleavage at site 1 and suppressed cleavage at site 2.

Redesigning nucleic acids.

A research program has applied the tools of synthetic organic chemistry to systematically modify the structure of DNA and RNA oligonucleotides to learn more about the chemical principles underlying their ability to store and transmit genetic information. Oligonucleotides (as opposed to nucleosides) have long been overlooked by synthetic organic chemists as targets for structural modification. Synthetic chemistry has now yielded oligonucleotides with 12 replicatable letters, modified backbones, and new insight into why Nature chose the oligonucleotide structures that she did.

Beneficial effects of testosterone undecanoate on the lipoprotein profiles in healthy elderly men. A placebo controlled study.

BACKGROUND AND METHODS: In order to assess the effects of testosterone undecanoate (TU; 120 mg/d orally for 2 months) on serum lipid, lipoprotein, and apolipoprotein levels in healthy elderly men, the placebo (PL) controlled study was performed on 37 elderly men, aged between 53 and 89 years. In all subjects venous blood samples were taken after an overnight (10 hours) fast and sera were stored -70 degrees C until analysis. RESULTS: In PL group, neither hormonal data nor lipid, lipoprotein, and apolipoprotein levels showed significant changes. After TU supplementation, serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and estradiol (E2) levels decreased from 198 +/- 30.7 mg/dl to 174 +/- 41.9 mg/dl (p < 0.05), from 111 +/- 18.14 mg/dl to 87.9 +/- 29.4 mg/dl (p < 0.01), and from 86.2 +/- 16.9 pmol/l to 70.5 +/- 18 pmol/l (p < 0.01), respectively. Statistically significant differences were not observed in the serum triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and apolipoprotein (apo) A-1 and apo B levels after TU treatment. The mean ratios TC/HDL-C and LDL-C/HDL-C as coronary risk factor criteria decreased significantly in the TU but not in the PL group. No obvious side effect was observed in those who took TU except for reported pyrosis in 2 of 17 elderly men. CONCLUSIONS: These data indicate that the increased serum levels of total testosterone (TT) produced by administration of TU, 120 mg/d orally for 2 months lead to suppressed levels of TC and LDL-C and E2 but not significantly changed levels of TC, HDL-C, apo A-1 and apo B. Thus, we conclude that TU may be an effective drug for protecting coronary heart disease in healthy elderly men with lowered TT and FT levels. It may also have beneficial effects for sexual function and behavior.