Intraluminal Stent Optimization for the Baerveldt Glaucoma Implant: An Experimental Study.

PRECIS: Our laboratory study determined the approximate suture diameter for use in intraluminal stenting of the Baerveldt glaucoma implant (BGI) to prevent postoperative hypotony. Commercial 3-0 monofilament nylon sutures which are commonly used may vary significantly outside of this diameter. PURPOSE: Postoperative hypotony is a complication of surgical treatment of glaucoma using the BGI. One method utilized to prevent early postoperative hypotony is intraluminal stenting of the implant with monofilament sutures. The present study attempted to determine optimal stent diameter in microns for 3-0 monofilament sutures to reduce outflow and thereby reduce the risk of postoperative hypotony using the BGI. MATERIALS AND METHODS: A laboratory bench model of the anterior chamber was utilized to measure the outflow rate of balanced salt solution through the BGI at pressures of 20 and 40 mm Hg while utilizing commercially available 3-0 monofilament nylon stents of various diameters. The BGI tube has an inner diameter of 300 µm. In addition, 3-0 nylon sutures were studied for variability by measuring the diameters at 10 equally spaced points along the length of each sample using a digital micrometer. RESULTS: Average experimental flow rates decreased with increasing intraluminal stent diameter and increased with increasing pressure. An intraluminal stent diameter of 250 µm yielded a flow rate of 40 µL/min at a nominal pressure of 20 mm Hg. Diameters of the tested 3-0 monofilament nylon sutures were all within the United States Pharmacopeia diameter range of 200 to 250 µm, but diameters varied significantly depending on the manufacturer. CONCLUSIONS: In our laboratory model, the optimal stent diameter to reduce aqueous flow to a level approaching the normal aqueous production is at least 250 µm. Secondarily, commercially available 3-0 monofilament nylon suture materials showed variable diameters within the United States Pharmacopeia diameter range.

Electrochemical synthesis of selenyl-dihydrofurans via anodic selenofunctionalization of allyl-naphthol/phenol derivatives and their anti-Alzheimer activity.

Herein, we report an eco-friendly, electrosynthetic approach for the intramolecular oxyselenylation of allyl-naphthol/phenol derivatives. This reaction proceeds with 0.2 equiv. of nBu4NClO4 as an electrolyte and Pt working electrodes in an undivided cell, resulting in the selenyl-dihydrofurans in good to excellent yields. Furthermore, several of the synthesized products presented a high percentage of acetylcholinesterase (AChE) inhibition, highlighting their potential anti-Alzheimer activity.

Photoinduced, Direct C(sp2 )-H Bond Azo Coupling of Imidazoheteroarenes and Imidazoanilines with Aryl Diazonium Salts Catalyzed by Eosin†Y.

Herein, a greener approach to the eosin Y-Na2 catalyzed, C(sp2 )-H bond azo coupling of imidazoheteroarene with aryl diazonium salts is described, under acid free conditions. This direct photoredox process resulted in the corresponding azo products in good to excellent yields. Besides, this new approach could also be applicable to anilines, which is a poorly reactive substrate by other methods. The main features of this reaction are that it provides high yields and is gram-scalable and applicable to biologically relevant imidazoheteroarenes and -anilines.

Rose Bengal catalysed photo-induced selenylation of indoles, imidazoles and arenes: a metal free approach.

In this report, the highly efficient Rose Bengal-catalysed C(sp2)-H selenylation of indoles, imidazoles and arenes was achieved using a half molar equiv. of diorganoyl diselenides. This metal-free, photo-induced protocol resulted in selenylated products in good to excellent yields. The reaction features are high yields, an atom-economic, gram-scalable and metal-free approach, and applicability to different biologically relevant (hetero)arenes.

Risk of Venous Thromboembolism Among Otolaryngology Patients vs General Surgery and Plastic Surgery Patients.

IMPORTANCE: Venous thromboembolism (VTE), which includes deep venous thrombosis or pulmonary embolism, is the number 1 cause of preventable death in surgical patients. Current guidelines from the American College of Chest Physicians provide VTE prevention recommendations that are specific to individual surgical subspecialties; however, no guidelines exist for otolaryngology. OBJECTIVE: To examine the rate of VTE for various otolaryngology procedures compared with an established average-risk field (general surgery) and low-risk field (plastic surgery). DESIGN, SETTING, AND PARTICIPANTS: This cohort study compared the rate of VTE after different otolaryngology procedures with those of general and plastic surgery in the American College of Surgeons National Surgical Quality Improvement Program from January 1, 2005, through December 31, 2013. We used univariate and multivariable logistic regression analysis of clinical characteristics, cancer status, and Caprini score to compare different risk stratification of patients. Data analysis was performed from May 1, 2016, to April 1, 2017. EXPOSURE: Surgery. MAIN OUTCOMES AND MEASURES: Thirty-day rate of VTE. RESULTS: A total of 1 295 291 patients, including 31 896 otolaryngology patients (mean [SD] age, 53.9 [16.7] years; 14 260 [44.7%] male; 21 603 [67.7%] white), 27 280 plastic surgery patients (mean [SD] age, 50.5 [13.9] years; 4835 [17.7%] male; 17 983 [65.9%] white), and 1 236 115 general surgery patients (mean [SD] age, 54.9 [17.2] years; 484 985 [39.2%] male; 867 913 [70.2%] white) were compared. The overall 30-day rate of VTE was 0.5% for otolaryngology compared with 0.7% for plastic surgery and 1.2% for general surgery. We identified a high-risk group for VTE in otolaryngology (n = 3625) that included free or regional tissue transfer, laryngectomy, composite resection, skull base surgery, and incision and drainage. High-risk otolaryngology patients experienced similar rates of VTE as general surgery patients across all Caprini risk levels. Low-risk otolaryngology patients (n = 28 271) experienced lower rates of VTE than plastic surgery patients across all Caprini risk levels. Malignant tumors were associated with VTE; however, the rates varied by cancer type and were 11-fold greater for cancers of the upper aerodigestive tract compared with thyroid cancers (odds ratio, 10.97; 95% CI, 7.38-16.31). Venous thromboembolism was associated with a 14-fold higher 30-day mortality among otolaryngology patients (5.1% mortality with VTE vs 0.4% mortality without VTE; difference, 4.7%; 95% CI of the difference, 2.2%-9.3%). CONCLUSIONS AND RELEVANCE: Most patients undergoing otolaryngology procedures are at low risk of VTE, indicating that guidelines for a low-risk population could be adapted to otolaryngology. Patients undergoing high-risk otolaryngology procedures should be considered as candidates for more aggressive VTE prophylaxis.

Direct, Metal-free C(sp2 )-H Chalcogenation of Indoles and Imidazopyridines with Dichalcogenides Catalysed by KIO3.

Herein, we report a greener protocol for the synthesis of 3-Se/S-indoles and imidazo[1,2-a]pyridines through direct C(sp2 )-H bond chalcogenation of heteroarenes with half molar equivalents of different dichalcogenides, using KIO3 as a non-toxic, easy-to-handle catalyst and a stoichiometric amount of glycerol. The reaction features are high yields, based on atom economy, easy performance on gram-scale, metal- and solvent-free conditions as well as applicability to different types of N-heteroarenes.

Metal- and Solvent-Free Approach to Access 3-Se/S-Chromones from the Cyclization of Enaminones in the Presence of Dichalcogenides Catalyzed by KIO3.

Herein, we describe a greener protocol for the one-pot synthesis of 3-Se/S-4H-chromen-4-ones. The desired products were obtained in good to excellent yields using 2-hydroxyphenyl enaminones and half equivalents of various odorless diorganyl dichalcogenides (S/Se) in the presence of glycerol (5 molar equiv) and KIO3 (15 mol %) as the catalyst under solvent-free conditions.

Solid-phase synthesis of reduced selenocysteine tetrapeptides and their oxidized analogs containing selenenylsulfide eight-membered rings.

A series of protected and reduced forms of model tetrapeptides that mimic the C-terminus of human thioredoxin reductases were obtained in good yields, using solid-phase peptide synthesis (SPPS). SPPS was performed on the Knorr Amide MBHA resin for Fmoc chemistry using especially protected cystein and selenocystein derivatives. All amino acids have been coupled according to the HBTU/HOBt/DIPEA method. Furthermore, the corresponding oxidized peptides containing eight-membered rings with intramolecular S-S and S-Se bridges were prepared via I[Formula: see text]/MeOH or DMSO/TFA oxidation, respectively.

In-vitro imaging of femoral artery nitinol stents for deformation analysis.

PURPOSE: Femoral artery stents are prone to fracture, and studying their deformations could lead to a better understanding of the cause of breakage. The present study sought to develop a method of imaging and analyzing stent deformation in vitro with use of a calibrated test device. MATERIALS AND METHODS: High-resolution (approximately 200 µm) volumetric data were obtained with a flat-panel detector-based C-arm computed tomography system. A nitinol stent placed in a testing device was imaged with various loads that caused bending, axial tension, and torsion. Semiautomatic software was developed to calculate the bending, extension, and torsion from the stent images by measuring the changes in the radius of curvature, eccentricity, and angular distortions. RESULTS: For the axial tension case, there was generally good agreement between the physical measurements and the image-based measurements. The bending measurements had better agreement at bend angles lower than 30°. For stent torsion, the hysteresis between the loading and unloading curves were larger for the image-based results compared with physical measurements. CONCLUSIONS: An imaging and analysis framework has been set up for the analysis of stent deformations that shows fairly good agreement between physical and image-based measurements.

In-vivo imaging of femoral artery nitinol stents for deformation analysis.

PURPOSE: The authors have developed a direct method to study femoral artery stent deformations in vivo. A previously described imaging and analysis approach based on a calibrated phantom was used to examine stents in human volunteers treated for atherosclerotic disease. In this pilot study, forces on stents were evaluated under different in-vivo flexion conditions. MATERIALS AND METHODS: The optimized imaging protocol for imaging with a C-arm computed tomography system was first verified in an in-vivo porcine stent model. Human data were obtained by imaging 13 consenting volunteers with stents in femoral vessels. The affected leg was imaged in straight and bent positions to observe stent deformations. Semiautomatic software was used to calculate the changes in bending, extension, and torsion on the stents for the two positions. RESULTS: For the human studies, tension and bending calculation were successful. Bending was found to compress stent lengths by 4% ± 3% (-14.2 to 1.5 mm), increase their average eccentricity by 10% ± 9% (0.12 to -0.16), and change their mean curvature by 27% ± 22% (0 to -0.005 mm(-1)). Stents with the greatest change in eccentricity and curvature were located behind the knee or in the pelvis. Torsion calculations were difficult because the stents were untethered and are symmetric. In addition, multiple locations in each stent underwent torsional deformations. CONCLUSIONS: The imaging and analysis approach developed based on calibrated in vitro measurements was extended to in-vivo data. Bending and tension forces were successfully evaluated in this pilot study.

Mission Hospital's code stroke team: implications for an aging population.

OBJECTIVE: To evaluate the success of an acute stroke program designed to streamline the evaluation and treatment of acute ischemic stroke patients, with particular regard to the risk of symptomatic intracerebral hemorrhage and discharge disposition based on age in those patients treated with acute stroke intervention. METHODS: Retrospective review of patients at Mission Hospitals in Asheville, North Carolina from January 2006 to October 2007 with sudden neurological deficit identified within six hours of onset. Data were obtained from Mission Hospital's in-house spreadsheet database and the American Stroke Association's "Get With the Guidelines" (GWTG) database. Patients were evaluated by a code stroke protocol that included early involvement of stroke-treating neurologists. A chart review of all code stroke patients established the number of patients treated with acute intervention, disposition, and follow-up information. RESULTS: Over the 22-month study period, there were 568 code stroke evaluations. Of all code stroke patients, 27.1% (n=154) were treated with an acute intervention for stroke, usually intravenous thrombolysis. We analyzed treated patients on the basis of age, with the younger age group (YAG) being 79 years or younger and the older age group (OAG) being 80 years or older. Of the patients treated with acute intervention, 58 (37.7%) were OAG. Discharge disposition varied with age: 42.7% of YAG patients went home alone or with home health assistance, whereas only 20.7% of OAG patients went home alone or with home health assistance. The inhospital mortality rate was 10.4% for YAG patients and 22.4% for OAG patients. Symptomatic intracerebral hemorrhage was noted in one patient under age 80 and one patient over age 80. This is a symptomatic hemorrhage rate of 1.3%. LIMITATIONS: This was a retrospective, observational, post hoc analysis without a standardized follow-up program. CONCLUSIONS: Our Code Stroke Team, with an inpatient neurology service, increased the proportion of stroke patients treated with acute intervention benchmarking with other GWTG participating hospitals in this time period. Aggressive stroke treatment with thrombolytic therapy in patients over age 80 did not show an increased rate of symptomatic intracerebral hemorrhage.

Temporal trends in public awareness of stroke: warning signs, risk factors, and treatment.

BACKGROUND AND PURPOSE: Delay in seeking medical attention after stroke symptom onset is the most important reason for low rates of thrombolytic use for ischemic stroke (IS) in the United States. This may be related to poor recognition of stroke symptoms, or to lack of awareness of time-sensitive stroke treatments. We describe public knowledge of t-PA as a treatment for IS, as well as changes over time in knowledge of stroke warning signs (WS) and risk factors (RF). METHODS: Survey respondents were drawn from our biracial population of 1.3 million using random-digit dialing in 1995, 2000, and 2005 to reflect the age, race, and gender distribution of stroke patients, based on an ongoing stroke incidence study in the same region. They were asked open-ended questions regarding stroke WS, RF, and, in 2005, specific questions regarding t-PA. Comparisons over time were made using chi(2) analysis, and were corrected for multiple comparisons. RESULTS: Over the 10-year study period, 6209 surveys were completed. Knowledge of WS and RF improved between 1995 and 2000. Between 2000 and 2005, knowledge did not improve significantly; however, there was a significant improvement in knowledge of 3 warning signs (12% in 1995 vs 16% in 2005, P=0.0004). In 2005, only 3.6% of those surveyed were able to independently name t-PA or "clot buster" when asked: "Suppose you were having a stroke. Do you know of any medication your doctor could give you into the vein to increase your chance of recovering from a stroke?"-although 19% claimed to have heard of t-PA once it was mentioned to them. CONCLUSIONS: Despite numerous national stroke public awareness campaigns, public knowledge of stroke WS and RF has not improved over the last 5 years. In addition, knowledge of t-PA as a treatment for IS is extremely poor. Public awareness messages in the future should focus on the possibility of urgent treatments, in addition to stroke WS and RF, so the public can translate their knowledge into action and present to medical attention more quickly. This may be the highest yield approach to increasing rates of treatment of IS with t-PA.

Synthesis of selenocysteine and its derivatives with an emphasis on selenenylsulfide (-Se-S-) formation.

A short survey of historic and current methods for the synthesis of selenocysteine, selenocystine, and derivatives and related compounds is presented, with an additional emphasis on the formation of selenocysteine-derived Se-S bridges. The majority of methods to the amino acid starts with protected and O-activated serine, but also other concepts are included such as radical or multicomponent strategies, the latter allowing also direct access to peptoids in one pot. Of special importance is the monomeric oxidative cyclization of selenocysteine-cysteine peptides to eight-membered and larger rings with a selenenylsulfide bridge, a crucial element in several selenoproteins.

Pulmonary embolism: computer-aided detection at multidetector row spiral computed tomography.

BACKGROUND: We aimed to evaluate the feasibility and performance of a computer-aided detection (CAD) tool for automated detection of segmental and subsegmental pulmonary emboli. METHODS: A CAD tool (ImageChecker CT, R2 Technology, Inc) for automated detection of pulmonary emboli was evaluated on multidetector-row CT studies of varying diagnostic quality in 23 patients (13 female, mean age 52 y) with pulmonary embolism (PE) and of 13 patients (all female, mean age 49 y) without PE. A collimation of 16 x 1 mm and a reconstructed section width of 1.25 mm had been used in each patient. The performance of the CAD tool for the detection of emboli in the segmental and subsegmental pulmonary arterial tree was assessed. Consensus reading of the same studies by 2 radiologists, with a third for adjudication, for the identification of segmental and subsegmental pulmonary emboli was used as the standard of reference. RESULTS: Consensus reading revealed 130 segmental pulmonary emboli and 107 subsegmental pulmonary emboli in the 23 patients with PE. All 23 patients with PE were correctly identified as having PE by the CAD system. In a vessel-by-vessel analysis, the sensitivity of the CAD algorithm was 92% (119/130) for the detection of segmental pulmonary emboli and 90% (92/107) for subsegmental pulmonary emboli. The overall specificity, positive predictive value (95% confidence interval) and negative predictive value (95% confidence interval) of the algorithm were 89.9%, 63.2% (57.9%-68.2%) and 97.7% (96.7%-98.4%), respectively. The average false positive rate of the CAD algorithm was 4.8 (range 1 to 9) false positive detection marks per case. CONCLUSION: CAD of segmental and subsegmental pulmonary emboli based on 1-mm multidetector-row CT studies is feasible. Application of CAD tools may improve the diagnostic accuracy and decrease the interpretation time of computed tomographic angiography for the detection of pulmonary emboli in the peripheral arterial tree and further enhance the acceptance of this test as the first line diagnostic modality for suspected PE.

Selenium in chemistry and biochemistry in comparison to sulfur.

What makes selenoenzymes--seen from a chemist's view--so special that they cannot be substituted by just more analogous or adapted sulfur proteins? This review compiles and compares physicochemical properties of selenium and sulfur, synthetic routes to selenocysteine (Sec) and its peptides, and comparative studies of relevant thiols and selenols and their (mixed) dichalcogens, required to understand the special role of selenium in selenoproteins on the atomic molecular level. The biochemically most relevant differences are the higher polarizability of Se- and the lower pKa of SeH. The latter has a strikingly different pH-dependence than thiols, with selenols being active at much lower pH. Finally, selected typical enzymatic mechanisms which involve selenocysteine are critically discussed, also in view of the authors' own results.

Influence of pH and flanking serine on the redox potential of S-S and S-Se bridges of Cys-Cys and Cys-Sec peptides.

In selenocysteine (Sec, U)-containing proteins the selenenylsulfide bridge and its reduced thiol-selenol counterpart are usually the significant species. An important role for serine as flanking amino acid in the redox potential of S-S and S-Se bridges was proposed for some thioredoxin reductases. To check the generality of this proposal, model tetrapeptides (GCCG, SCCG, GCCS, SCCS, GCUG, SCUG, GCUS, SCUS) were synthesized, including the GCUG sequence of human thioredoxin reductase. The influence on the redox potential of S-Se and S-S bridges as a function of pH and of serine at different positions reveals (i) a strong general pH dependence, and (ii) a significant influence of flanking serine on disulfide only at basic pH.

The use of standardized patients for mock oral board exams in neurology: a pilot study.

BACKGROUND: Mock oral board exams, fashioned after the live patient hour of the American Board of Psychiatry and Neurology exam, are commonly part of resident assessment during residency training. Exams using real patients selected from clinics or hospitals are not standardized and do not allow comparisons of resident performance across the residency program. We sought to create a standardized patient mock oral board exam that would allow comparison of residents' clinical performance. METHODS: Three cases were created and then used for this mock oral boards exercise utilizing trained standardized patients. Residents from the University of Cincinnati and Indiana University participated in the exam. Residents were scored by attending physician examiners who directly observed the encounter with the standardized patient. The standardized patient also assessed each resident. A post-test survey was administered to ascertain participant's satisfaction with the examination process. RESULTS: Resident scores were grouped within one standard deviation of the mean, with the exception of one resident who was also subjectively felt to "fail" the exam. In exams with two faculty "evaluators", scores were highly correlated. The survey showed satisfaction with the examination process in general. CONCLUSION: Standardized patients can be used for mock oral boards in the live patient format. Our initial experience with this examination process was positive. Further testing is needed to determine if this examination format is more reliable and valid than traditional methods of assessing resident competency.

Eligibility for recombinant tissue plasminogen activator in acute ischemic stroke: a population-based study.

BACKGROUND AND PURPOSE: Acute ischemic stroke patients are infrequently treated with recombinant tissue plasminogen activator (rtPA). We present unique population-based data regarding the eligibility of ischemic stroke patients for rtPA treatment. METHODS: All ischemic strokes presenting to an emergency department (ED) within a biracial population of 1.3 million were identified. The patient was considered eligible for rtPA on the basis of exclusion criteria from the National Institute of Neurological Disorders and Stroke rtPA trial. RESULTS: Of 2308 ischemic strokes, 1849 presented to an ED. Only 22% of all ischemic strokes in the population arrived in the ED in <3 hours from symptom onset; of these, 209 (51%) were ineligible for rtPA on the basis of mild stroke severity, medical and surgical history, or blood tests. CONCLUSIONS: In our population in 1993 to 1994, 8% of all ischemic stroke patients presented to an ED within 3 hours and met other eligibility criteria for rtPA. Even if time were not an exclusion for rtPA, only 29% of all ischemic strokes in our population would have otherwise been eligible for rtPA.