Spectroelectrochemical determination of thiolate self-assembled monolayer adsorptive stability in aqueous and non-aqueous electrolytes.

Self-assembled monolayers (SAM) are ubiquitous in studies of modified electrodes for sensing, electrocatalysis, and environmental and energy applications. However, determining their adsorptive stability is crucial to ensure robust experiments. In this work, the stable potential window (SPW) in which a SAM-covered electrode can function without inducing SAM desorption was determined for aromatic SAMs on gold electrodes in aqueous and non-aqueous solvents. The SPWs were determined by employing cyclic voltammetry, attenuated total reflectance surface-enhanced infrared absorption spectroscopy (ATR-SEIRAS), and surface plasmon resonance (SPR). The electrochemical and spectroscopic findings concluded that all the aromatic SAMs used displayed similar trends and SPWs. In aqueous systems, the SPW lies between the reductive desorption and oxidative desorption, with pH being the decisive factor affecting the range of the SPW, with the widest SPW observed at pH 1. In the non-aqueous electrolytes, the desorption of SAMs was observed to be slow and progressive. The polarity of the solvent was the main factor in determining the SPW. The lower the polarity of the solvent, the larger the SPW, with 1-butanol displaying the widest SPW. This work showcases the power of spectroelectrochemical analysis and provides ample future directions for the use of non-polar solvents to increase SAM stability in electrochemical applications.

Monitoring SEIRAS on a Graphitic Electrode for Surface-Sensitive Electrochemistry: Real-Time Electrografting.

The ubiquity of graphitic materials in electrochemistry makes it highly desirable to probe their interfacial behavior under electrochemical control. Probing the dynamics of molecules at the electrode/electrolyte interface is possible through spectroelectrochemical approaches involving surface-enhanced infrared absorption spectroscopy (SEIRAS). Usually, this technique can only be done on plasmonic metals such as gold or carbon nanoribbons, but a more convenient substrate for carbon electrochemical studies is needed. Here, we expanded the scope of SEIRAS by introducing a robust hybrid graphene-on-gold substrate, where we monitored electrografting processes occurring at the graphene/electrolyte interface. These electrodes consist of graphene deposited onto a roughened gold-sputtered internal reflection element (IRE) for attenuated total reflectance (ATR) SEIRAS. The capabilities of the graphene-gold IRE were demonstrated by successfully monitoring the electrografting of 4-amino-2,2,6,6-tetramethyl-1-piperidine N-oxyl (4-amino-TEMPO) and 4-nitrobenzene diazonium (4-NBD) in real time. These grafts were characterized using cyclic voltammetry and ATR-SEIRAS, clearly showing the 1520 and 1350 cm-1 NO2 stretches for 4-NBD and the 1240 cm-1 C-C, C-C-H, and N-È® stretch for 4-amino-TEMPO. Successful grafts on graphene did not show the SEIRAS effect, while grafting on gold was not stable for TEMPO and had poorer resolution than on graphene-gold for 4-NBD, highlighting the uniqueness of our approach. The graphene-gold IRE is proficient at resolving the spectral responses of redox transformations, unambiguously demonstrating the real-time detection of surface processes on a graphitic electrode. This work provides ample future directions for real-time spectroelectrochemical investigations of carbon electrodes used for sensing, energy storage, electrocatalysis, and environmental applications.

The association between race/ethnicity and peripartum hysterectomy and the risk of perioperative complications.

OBJECTIVE: To compare perioperative outcomes by patient race/ethnicity. METHODS: A retrospective cohort study identified 7 331 638 childbirth hospitalizations for women aged 12-55 years in the USA between 2004-2014. Peripartum hysterectomy, in-hospital mortality, perioperative complications, length of stay, and cost of hysterectomy data were analyzed using SAS. RESULTS: Among childbirth hospitalizations (52.9% white, 13.5% black, 23.0% Hispanic, 5.2% Asian, and 5.4% other), peripartum hysterectomy occurred in 6619. The incidence of peripartum hysterectomy was 90.3 (95% confidence interval [CI] 87.7-93.0) per 100 000 hospitalizations, and higher for black (111.0, 95% CI 104.5-117.4), Hispanic (104.9, 95% CI 99.1-110.8), and Asian women (119.6, 95% CI 109.1-130.2) compared to whites (75.7, 95% CI 72.8-78.5). After adjustment, Hispanic women had an 18% higher odds of undergoing peripartum hysterectomy (odds ratio [OR] 1.18, 95% CI 1.08-1.29; P=0.004) than white women. Non-white women had a 2-3-fold higher odds of in-hospital mortality (ORblack 2.76, 95% CI 1.44-5.30; ORHispanic 1.99, 95% CI 1.04-3.82; ORAsian+other 2.44, 95% CI 1.11-5.40. Black and Asian/other women were more likely to undergo blood transfusions. CONCLUSION: Women of color have higher rates of peripartum hysterectomy and experience higher rates of poor perioperative outcomes and mortality.

Local delivery of cancer-cell glycolytic inhibitors in high-grade glioma.

BACKGROUND: 3-bromopyruvate (3-BrPA) and dichloroacetate (DCA) are inhibitors of cancer-cell specific aerobic glycolysis. Their application in glioma is limited by 3-BrPA's inability to cross the blood-brain-barrier and DCA's dose-limiting toxicity. The safety and efficacy of intracranial delivery of these compounds were assessed. METHODS: Cytotoxicity of 3-BrPA and DCA were analyzed in U87, 9L, and F98 glioma cell lines. 3-BrPA and DCA were incorporated into biodegradable pCPP:SA wafers, and the maximally tolerated dose was determined in F344 rats. Efficacies of the intracranial 3-BrPA wafer and DCA wafer were assessed in a rodent allograft model of high-grade glioma, both as a monotherapy and in combination with temozolomide (TMZ) and radiation therapy (XRT). RESULTS: 3-BrPA and DCA were found to have similar IC50 values across the 3 glioma cell lines. 5% 3-BrPA wafer-treated animals had significantly increased survival compared with controls (P = .0027). The median survival of rats with the 50% DCA wafer increased significantly compared with both the oral DCA group (P = .050) and the controls (P = .02). Rats implanted on day 0 with a 5% 3-BrPA wafer in combination with TMZ had significantly increased survival over either therapy alone. No statistical difference in survival was noted when the wafers were added to the combination therapy of TMZ and XRT, but the 5% 3-BrPA wafer given on day 0 in combination with TMZ and XRT resulted in long-term survivorship of 30%. CONCLUSION: Intracranial delivery of 3-BrPA and DCA polymer was safe and significantly increased survival in an animal model of glioma, a potential novel therapeutic approach. The combination of intracranial 3-BrPA and TMZ provided a synergistic effect.

Tandem deprotection-dimerization-macrocyclization route to C(2) symmetric cyclo-tetrapeptides.

Dimerization-macrocyclization has been a long-standing problem in the cyclization of peptides since, together with the desired cyclic product, many cyclic oligomers and linear polymers may also be formed during the reaction. Therefore, the development of a process that affords the cyclic dimer predominantly is difficult. A novel and versatile strategy for the synthesis of symmetric cyclo-tetrapeptides by palladium-promoted tandem deprotection/cyclo-dimerization from readily available Cbz-dipeptidoyl benzotriazolides is reported (Cbz=carboxybenzyl).

Conformationally assisted lactamizations for the synthesis of symmetrical and unsymmetrical bis-2,5-diketopiperazines.

Open-chain N-Cbz-protected-peptidoyl benzotriazolides are converted by a novel lactamization strategy using proline as a turn introducer into both symmetrical (5a-c and 11a-c) and unsymmetrical (19a-e) bis-2,5-diketopiperazines (bis-2,5-DKPs), previously recognized as difficult targets.

Measures of health sciences journal use: a comparison of vendor, link-resolver, and local citation statistics.

OBJECTIVE: Libraries require efficient and reliable methods to assess journal use. Vendors provide complete counts of articles retrieved from their platforms. However, if a journal is available on multiple platforms, several sets of statistics must be merged. Link-resolver reports merge data from all platforms into one report but only record partial use because users can access library subscriptions from other paths. Citation data are limited to publication use. Vendor, link-resolver, and local citation data were examined to determine correlation. Because link-resolver statistics are easy to obtain, the study library especially wanted to know if they correlate highly with the other measures. METHODS: Vendor, link-resolver, and local citation statistics for the study institution were gathered for health sciences journals. Spearman rank-order correlation coefficients were calculated. RESULTS: There was a high positive correlation between all three data sets, with vendor data commonly showing the highest use. However, a small percentage of titles showed anomalous results. DISCUSSION AND CONCLUSIONS: Link-resolver data correlate well with vendor and citation data, but due to anomalies, low link-resolver data would best be used to suggest titles for further evaluation using vendor data. Citation data may not be needed as it correlates highly with other measures.

Prognostic value of intraoperative renal tissue oxygenation measurement on early renal transplant function.

Ischemia time is a prognostic factor in renal transplantation for postoperative graft function and survival. Kidney transplants from living donors have a higher survival rate than deceased donor kidneys probably because of shorter ischemia time. We hypothesized that measurement of intraoperative kidney oxygenation (µHbO(2) ) and microvascular perfusion predicts postoperative graft function. We measured microvascular hemoglobin oxygen saturation by reflectance spectrophotometry and microcirculatory kidney perfusion by laser Doppler flowmetry 5 and 30min after kidney reperfusion on the organ surface in 53 renal transplant patients including 19 grafts from living donors. These values were related to systemic hemodynamics, cold ischemia time (cit), early postoperative graft function and length of hospital stay. µHbO(2) improved 30 min after reperfusion compared to 5 min (from 67% to 71%, P < 0.05). µHbO(2) correlated with mean arterial blood pressure and central venous pH (P < 0.01). Most importantly, µHbO(2) was significantly higher in kidneys from living compared with deceased donors (74% vs. 63%) and in kidneys without vs. with biopsy-proven postoperative rejection (71% vs. 45%, P < 0.001). Finally, µHbO(2) correlated positively with cit and postoperative creatinine clearance and negatively with postoperative plasma creatinine, need for hemodialysis and length of hospital stay. Our results suggest higher oxygen extraction and thus oxygen demand of the grafts shortly after reperfusion. The intraoperative measurement of tissue oxygenation in kidney transplants is predictive of early postoperative graft function. Future studies should evaluate the potential effect of intraoperative therapeutic maneuvers to improve organ tissue oxygenation in renal transplantation.

Nociceptin produces antinociception after spinal administration in amphibians.

Nociceptin, also known as orphanin FQ, is a opioid-like neuropeptide that mediates its effects at the nociceptin receptor, a member of the G protein-coupled receptor superfamily. In mammals, nociceptin produces analgesia after spinal administration, however the role of nociceptin and nociceptin receptors in the modulation of noxious stimuli in non-mammalian species has not been examined. In an amphibian pain model using the acetic acid test with Rana pipiens, nociceptin and nociceptin1-13 amide produced dose-dependent antinociception (1-100 nmol), blocked by the nociceptin antagonist, [Nphe1]-nociceptin1-13 amide (30 nmol), but not the opioid antagonist, naltrexone (100 nmol/g, s.c.). Conversely, the antinociceptive effects of micro, delta, and kappa opioid receptor agonists were not blocked by the nociceptin antagonist. Nociceptin and nociceptin1-13 amide were the least potent of the opioid agonists tested. These studies demonstrate that spinal nociceptin receptors and not opioid receptors mediate the antinociceptive effect of nociceptin. Considered with previous findings, these behavioral data supports a role for nociceptin inhibition of spinal nociception in amphibians and perhaps all vertebrates.

Intraoperative cerebral high-intensity transient signals and postoperative cognitive function: a systematic review.

BACKGROUND: Much attention in the literature has focused on the relationship between perioperative microemboli during cardiac and vascular surgery and postoperative cognitive decline. Transcranial Doppler ultrasonography (TCD) has been used to measure high-intensity transient signals (HITS), which represent microemboli during cardiac, vascular, and orthopedic surgery. The purpose of this study was to systematically examine the literature with respect to HITS and postoperative cognitive function. METHODS: Systematic PubMed searches identified articles related to the use of TCD and cognitive function in the surgical setting. RESULTS: The literature remains largely undecided on the role of HITS and cognitive impairment after surgery, with most studies being underpowered to show a relationship. Although the cognitive effects of HITS may be difficult to detect, subclinical microemboli present potential harm, which may be modifiable. CONCLUSIONS: TCD represents a tool for intraoperative cerebral monitoring to reduce the number of HITS during surgery.

Low-intensity pulsed ultrasound accelerates and a nonsteroidal anti-inflammatory drug delays knee ligament healing.

BACKGROUND: Low-intensity pulsed ultrasound and nonsteroidal anti-inflammatory drugs are used to treat ligament injuries; however, their individual and combined effects are not established. HYPOTHESES: Low-intensity pulsed ultrasound accelerates ligament healing, a nonsteroidal anti-inflammatory drug delays healing, and the nonsteroidal anti-inflammatory drug inhibits the beneficial effect of low-intensity pulsed ultrasound. STUDY DESIGN: Controlled laboratory study. METHODS: Sixty adult rats underwent bilateral transection of their knee medial collateral ligaments. Animals were divided into 2 drug groups and treated 5 d/wk with celecoxib (5 mg/kg) mixed in a vehicle solution (NSAID group) or vehicle alone (VEH group). One to 3 hours after drug administration, all animals were treated with unilateral active low-intensity pulsed ultrasound and contralateral inactive low-intensity pulsed ultrasound. Equal numbers of animals from each drug group were mechanically tested at 2 weeks (n = 14/group), 4 weeks (n = 8/group), and 12 weeks (n = 8/group) after injury. RESULTS: Ultrasound and drug intervention did not interact to influence ligament mechanical properties at any time point. After 2 weeks of intervention, ligaments treated with active low-intensity pulsed ultrasound were 34.2% stronger, 27.0% stiffer, and could absorb 54.4% more energy before failure than could ligaments treated with inactive low-intensity pulsed ultrasound, whereas ligaments from the NSAID group could absorb 33.3% less energy than could ligaments from the VEH group. There were no ultrasound or drug effects after 4 and 12 weeks of intervention. CONCLUSIONS: Low-intensity pulsed ultrasound accelerated but did not improve ligament healing, whereas the nonsteroidal anti-inflammatory drug delayed but did not impair healing. When used in combination, the beneficial low-intensity pulsed ultrasound effect was cancelled by the detrimental nonsteroidal anti-inflammatory drug effect. CLINICAL RELEVANCE: Low-intensity pulsed ultrasound after ligament injury may facilitate earlier return to activity, whereas non-steroidal anti-inflammatory drugs may elevate early reinjury risk.