Postoperative pain control and opioid use with transversus abdominis plane block and scheduled multimodal pain management in patients undergoing cesarean section.

OBJECTIVE: The impact of a transversus abdominis plane (TAP) block in patients undergoing cesarean section requires further evaluation. The aim of this study was to compare postoperative pain scores and opioid use in cesarean surgery patients undergoing either a TAP block and scheduled multimodal pain management (SMPM) or SMPM alone. METHODS: In this retrospective, dual cohort study, cesarean surgery patients underwent neuraxial anesthesia and a TAP block (SMPM/TAP) or SMPM; the TAP block incorporated ropivacaine (20-30 mL) administered bilaterally. The group analyses involved a comparison of postoperative pain scores using the visual analog scale and opioid consumption at 24 and 24-48 h. RESULTS: There were 94 (52.8%) patients in the SMPM/TAP group and 84 (47.2%) subjects in the SMPM alone group. At 24 h postoperatively, the SMPM/TAP group exhibited significantly lower pain scores (4.07 vs 4.54) than the SMPM group (P < 0.001) and reduced opioid consumption (2.29 vs 3.28 mg; P < 0.001). However, at 24-48 h, the SMPM group demonstrated lower pain scores (5.46 vs 5.98) compared to the SMPM/TAP group (P < 0.001) and reduced opioid consumption (8.75 vs 10.21 mg; P < 0.001); overall opioid consumption was higher (12.50 vs 12.02 mg) in the SMPM/TAP group (P < 0.001). CONCLUSION: The TAP block improved cesarean surgery patients' pain scores and reduced opioid consumption at 24 h postoperatively but the effect of the TAP block was ephemeral as the SMPM/TAP group exhibited inferior pain scores and greater opioid consumption compared to the SMPM group at 24-48 h postoperatively.

Comparison of the infectivity of Trypanosoma cruzi insect-derived metacyclic trypomastigotes after mucosal and cutaneous contaminative challenges.

Trypanosoma cruzi infects humans when infected triatomine vector excreta contaminate breaks in skin or mucosal surfaces. T. cruzi insect-derived metacyclic trypomastigotes (IMT) invade through gastric mucosa after oral challenges without any visible inflammatory changes, while cutaneous and conjunctival infections result in obvious local physical signs. In this study we compared the infectivity of T. cruzi IMT in mice after cutaneous and oral contaminative challenges simulating natural infections. The 50% infective dose (ID50) for oral challenge was 100 fold lower than the ID50 for cutaneous challenge, indicating that oral mucosal transmission is more efficient than cutaneous transmission.

Myo4p is a monomeric myosin with motility uniquely adapted to transport mRNA.

The yeast Saccharomyces cerevisiae uses two class V myosins to transport cellular material into the bud: Myo2p moves secretory vesicles and organelles, whereas Myo4p transports mRNA. To understand how Myo2p and Myo4p are adapted to transport physically distinct cargos, we characterize Myo2p and Myo4p in yeast extracts, purify active Myo2p and Myo4p from yeast lysates, and analyze their motility. We find several striking differences between Myo2p and Myo4p. First, Myo2p forms a dimer, whereas Myo4p is a monomer. Second, Myo4p generates higher actin filament velocity at lower motor density. Third, single molecules of Myo2p are weakly processive, whereas individual Myo4p motors are nonprocessive. Finally, Myo4p self-assembles into multi-motor complexes capable of processive motility. We show that the unique motility of Myo4p is not due to its motor domain and that the motor domain of Myo2p can transport ASH1 mRNA in vivo. Our results suggest that the oligomeric state of Myo4p is important for its motility and ability to transport mRNA.

Feasibility and Acceptability of Tele-Colposcopy on the Caribbean Coast of Nicaragua: A Descriptive Mixed-Methods Study.

Background: Cervical cancer, a preventable cancer of disparities, is the primary cause of cancer death for women in Nicaragua. Clinics and personnel in rural and remote Nicaragua may not be accessible to perform recommended screening or follow-up services. Objective: To assess acceptability and feasibility of integrating innovations for high-quality screening and treatment follow-up (tele-colposcopy) into existing pathways on Nicaragua's Caribbean Coast within the context of the National Cervical Cancer Control Program. Methods: Provider focus groups, key informant interviews, and environmental scans were conducted for 13 clinics on the Caribbean Coast of Nicaragua. Topics discussed included a smartphone-based mobile colposcope (MobileODT hardware and mobile platform), mobile connectivity capacity, clinic resources, provider acceptability, and current diagnostic and clinical protocols. We tested device connectivity through image upload availability and real-time video connection and simulated clinical encounters utilizing MobileODT and a low-cost cervical simulator. We developed a database of colposcopic images to establish feasibility of integrating this database and clinical characteristics into the cervical cancer registry. Results: Provider acceptability of integrating tele-colposcopy into existing cancer control efforts was high. Image upload connectivity varied by location (mean = 1 h 9 min). Most clinics had running water (84.6%) and consistent electricity (92.3%), but some did not have access to landline telephones (53.8%). Conclusions: As faster connectivity becomes available in remote settings, Mobile Health tools such as tele-colposcopy will be increasingly feasible to provide access to high-quality cervical cancer follow-up. World Health Organization guidance on integrating technology into existing programs will remain important to ensure programmatic efficacy, local relevance, and sustainability.

Beyond broadband: digital inclusion as a driver of inequities in access to rural cancer care.

PURPOSE: Rural cancer survivors have worse quality of life than their urban counterparts. Telemedicine is a potential solution to connecting rural residents with specialized cancer providers during the survivorship period, but limitations in broadband may stifle the impact. Using data from a feasibility study evaluating a telemedicine intervention aimed at connecting rural Virginia cancer survivors with their care team located at a cancer center associated with an academic medical center, we sought to evaluate the ability of rural survivors to access the intervention and suggest strategies for improving access to rural cancer survivorship care. METHODS: We used a descriptive design with geospatial and quantitative methods to understand broadband access, driving time to a satellite telemedicine site, and ability to utilize a borrowed cellular-enabled tablet to participate in the intervention for cancer survivors living in Central Virginia. RESULTS: Our study participants resided in census tracts where an average of 58% of households have adequate broadband access necessary to support a telemedicine videoconferencing intervention. Average driving time to the nearest telemedicine site was 29.6 min. Those who utilized the borrowed tablet experienced considerable difficulty with utilizing the technology. CONCLUSIONS: Rural cancer populations do not have equal access to a cancer survivorship telemedicine intervention. IMPLICATIONS FOR CANCER SURVIVORS: Telemedicine interventions aimed at connecting cancer survivors with their academic medical center-based cancer providers may be ineffective if survivors do not have access to either fixed broadband or a satellite clinic. Future research needs to evaluate other sites from which rural survivors can connect, such as rural public libraries.

Myo4p and She3p are required for cortical ER inheritance in Saccharomyces cerevisiae.

Myo4p is a nonessential type V myosin required for the bud tip localization of ASH1 and IST2 mRNA. These mRNAs associate with Myo4p via the She2p and She3p proteins. She3p is an adaptor protein that links Myo4p to its cargo. She2p binds to ASH1 and IST2 mRNA, while She3p binds to both She2p and Myo4p. Here we show that Myo4p and She3p, but not She2p, are required for the inheritance of cortical ER in the budding yeast Saccharomyces cerevisiae. Consistent with this observation, we find that cortical ER inheritance is independent of mRNA transport. Cortical ER is a dynamic network that forms cytoplasmic tubular connections to the nuclear envelope. ER tubules failed to grow when actin polymerization was blocked with the drug latrunculin A (Lat-A). Additionally, a reduction in the number of cytoplasmic ER tubules was observed in Lat-A-treated and myo4Delta cells. Our results suggest that Myo4p and She3p facilitate the growth and orientation of ER tubules.

An evaluation of least-squares fitting methods in XAFS spectroscopy: iron-based SBA-15 catalyst formulations.

A detailed comparison has been made of determinations by (57)Fe Mössbauer spectroscopy and four different XAFS spectroscopic methods of %Fe as hematite and ferrihydrite in 11 iron-based SBA-15 catalyst formulations. The four XAFS methods consisted of least-squares fitting of iron XANES, d(XANES)/dE, and EXAFS (k(3)chi and k(2)chi) spectra to the corresponding standard spectra of hematite and ferrihydrite. The comparison showed that, for this particular application, the EXAFS methods were superior to the XANES methods in reproducing the results of the benchmark Mössbauer method in large part because the EXAFS spectra of the two iron-oxide standards were much less correlated than the corresponding XANES spectra. Furthermore, the EXAFS and Mössbauer results could be made completely consistent by inclusion of a factor of 1.3+/-0.05 for the ratio of the Mössbauer recoilless fraction of hematite relative to that of ferrihydrite at room temperature (293K). This difference in recoilless fraction is attributed to the nanoparticle nature of the ferrihydrite compared to the bulk nature of the hematite. Also discussed are possible alternative non-least-squares XAFS methods for determining the iron speciation in this application as well as criteria for deciding whether or not least-squares XANES methods should be applied for the determination of element speciation in unknown materials.

Increased type III TGF-ß receptor shedding decreases tumorigenesis through induction of epithelial-to-mesenchymal transition.

The type III TGF-ß receptor (TßRIII) is a TGF-ß co-receptor that presents ligand to the type II TGF-ß receptor to initiate signaling. TßRIII also undergoes ectodomain shedding to release a soluble form (sTßRIII) that can bind ligand, sequestering it away from cell surface receptors. We have previously identified a TßRIII extracellular mutant that has enhanced ectodomain shedding ("super shedding (SS)"-TßRIII-SS). Here, we utilize TßRIII-SS to study the balance of cell surface and soluble TßRIII in the context of lung cancer. We demonstrate that expressing TßRIII-SS in lung cancer cell models induces epithelial-to-mesenchymal transition (EMT) and that these TßRIII-SS (EMT) cells are less migratory, invasive and adhesive and more resistant to gemcitabine. Moreover, TßRIII-SS (EMT) cells exhibit decreased tumorigenicity but increased growth rate in vitro and in vivo. These studies suggest that the balance of cell surface and soluble TßRIII may regulate a dichotomous role for TßRIII during cancer progression.

Advances in magnetic resonance imaging methods for the evaluation of bipolar disorder.

This article reviews the current state of magnetic resonance imaging techniques as applied to bipolar disorder. Addressed are conventional methods of structural neuroimaging and recently developed techniques. This latter group comprises volumetric analysis, voxel-based morphometry, the assessment of T2 white matter hyperintensities, shape analysis, cortical surface-based analysis, and diffusion tensor imaging. Structural analysis methods used in magnetic resonance imaging develop exponentially, and now present opportunities to identify disease-specific neuroanatomic alterations. Greater acuity and complementarity in measuring these alterations has led to the generation of further hypotheses regarding the pathophysiology of bipolar disorder. Included in the summary of findings is consideration of a resulting neuroanatomic model. Integrative issues and future directions in this relatively young field, including multi-modal approaches enabling us to produce more comprehensive results, are discussed.

Enhancement in the reducibility of cobalt oxides on a mesoporous silica supported cobalt catalyst.

The silylation of SBA-15 enhances the reducibility of cobalt oxides on a SBA-15 supported cobalt catalyst, and consequently increases the catalytic activity for Fischer-Tropsch synthesis of hydrocarbons from syngas and selectivity for longer chain products.

Personal, health, academic, and environmental predictors of stress for residence hall students.

The authors studied contributors to stress among undergraduate residence hall students at a midwestern, land grant university using a 76-item survey consisting of personal, health, academic, and environmental questions and 1 qualitative question asking what thing stressed them the most. Of 964 students selected at random, 462 (48%) responded to the survey. The authors weighted data to reflect the overall university-wide undergraduate population (55% men, 12% minority or international, and 25% freshmen). Women and US citizens experienced greater stress than did men and non-US citizens, respectively. Frequency of experiencing chronic illness, depression, anxiety disorder, seasonal affective disorder, mononucleosis, and sleep difficulties were significant stress predictors. Although alcohol use was a positive predictor, drug use was a negative predictor of stress. Both a conflict and a satisfactory relationship with a roommate, as well as a conflict with a faculty or staff member, were also significant predictors of stress.

Genetic control of neutrophil superoxide production in diabetes-resistant ALR/Lt mice.

The neutrophil oxidative burst reaction differentiates ALR/Lt mice, known for an unusual systemic elevation of antioxidant defenses, from ALS/Lt mice, a related strain known for reduced ability to withstand oxidative stress. Neutrophils from marrow of ALS mice produced a normal neutrophil oxidative burst following phorbol ester stimulation. In contrast, ALR mice exhibited a markedly suppressed superoxide burst. F1 progeny from reciprocal outcrosses between ALR and ALS mice exhibited an intermediate burst level, higher than ALR but significantly lower than ALS. To elucidate the genetic basis for this strain difference, F1 mice were backcrossed to ALS mice, and marrow neutrophils isolated from the progeny were phenotyped for oxidative burst capacity. A genome-wide sweep using polymorphic markers distinguishing the two parental strains was performed to map the trait. A 1:1 phenotypic distribution was observed, and a locus (Suppressor of superoxide production, Susp) controlling this phenotype was mapped to Chromosome 3 near D3Mit241 at 33.1 cM. This locus probably represents an important regulatory element in the overall ALR strain resistance to oxidative stress, since diminished ability to mount a neutrophil burst in backcross segregants correlated with elevated hepatic superoxide dismutase 1 (SOD1) activity, an ALR strain characteristic.

Decision biases and persistent illicit drug use: an experimental study of distributed choice and addiction.

This experiment tested the hypothesis that differences in drug use are correlated with differences in decision making. The subjects were 22 drug clinic patients who had used either opiates or stimulants for an average of 10 years, and 21 community residents who reported that they had rarely used illicit addictive drugs. The procedure consisted of a series of binary choices with two consequences; they earned money and determined the intervals that separated choice trials. Each choice earned the same amount of money, but one initiated a shorter delay to the next trial, whereas the other initiated a shorter delay as averaged over the next two trials. Shorter delays were advantageous in that they increased the overall rate of earnings and they reduced the time spent waiting for the next trial. Thus, one choice was better from the perspective of the current trial, while the other choice was better from the perspective of two or more consecutive trials. Drug-clinic patients were more likely to favor the one-trial solution compared with control subjects, who were more likely to favor the two-trial solution. There were five different choice games, with different versions varying in the magnitude of the advantage for switching from the two-trial to the one-trial solution. Drug clinic and control subjects differed most in the games in which the immediate advantage of the one-trial solution was larger, and all subjects were more likely to choose the global solution when the incentive for switching to the one-trial solution was lower. The results support the view that individual differences in decision making influence the course of illicit drug use.

Effect of Conformational Constraints on Gated Electron Transfer Kinetics. 2. Copper(II/I) Complexes with Phenyl-Substituted [14]aneS(4) Ligands in Acetonitrile(1).

Kinetic studies have been conducted in acetonitrile on the electron-transfer reactions of five copper(II/I) complexes involving ligands in which either a benzene or a cyclohexane ring, or both, have been substituted into the ligand backbone of the 14-membered tetrathiamacrocycle [14]aneS(4). The specific ligands utilized in this work include 2,3-benzo-1,4,8,11-tetrathiacyclotetradecane (bz-[14]aneS(4)), 2,3-trans-cyclohexano-1,4,8,11-tetrathiacyclotetradecane (trans-cyhx-[14]aneS(4)), 2,3-benzo-9,10-trans-cyclohexano-1,4,8,11-tetrathiacyclotetradecane (bz,trans-cyhx-[14]aneS(4)), 2,3-benzo-9,10-cis-cyclohexano-1,4,8,11-tetrathiacyclotetradecane (bz,cis-cyhx-[14]aneS(4)), and 2,3-cis-9,10-trans-dicyclohexano-1,4,8,11-tetrathiacyclotetradecane (cis, trans-dicyhx-[14]aneS(4)). Each Cu(II/I)L system has been reacted with three separate reducing agents and three separate oxidizing agents to examine the effect of driving force upon the kinetic parameters. The Marcus relationship has been applied to each cross-reaction rate constant to estimate the apparent self-exchange rate constant, k(11), for each Cu(II/I)L system. For all but one of the five systems, the k(11) values obtained from the three reduction reactions are in virtual agreement with the corresponding value obtained for the oxidation reaction with the smallest driving force. As the driving force for Cu(I)L oxidation increases, a smaller k(11) value is calculated for each system. This behavior is consistent with our previously proposed dual-pathway square scheme mechanism in which a significant conformational change occurs as a separate step preceding electron transfer in the case of Cu(I)L oxidation. Although direct observation of conformationally-gated electron transfer was not attained for any of the five systems included in the current work, limits for the rate constant for conformational change have been estimated from the conditions required to change the apparent pathway for the oxidation kinetics. These limits show that the Cu(I)L complex involving a single phenyl substituent (bz-[14]aneS(4)) exhibits a much slower conformational change than do any of the other systems included in this study. The implications of this observation are discussed.

Electron-Transfer Kinetics and Thermodynamic Characterization of Copper(II/I) Complexes with Acyclic Tetrathiaethers in Aqueous Solution.

The kinetics of a series of Cu(II/I)-acyclic tetrathiaether complexes reacting with several oxidizing and reducing reagents have been examined in aqueous solution at 25 degrees C. This investigation has included a re-examination of Cu(II/I)(Me(2)-2,3,2-S(4)) (Me(2)-2,3,2-S(4) = 2,5,9,12-tetrathiatridecane = L12a), containing the ethylene-trimethylene-ethylene bridging sequence, plus three newly synthesized ligands containing an alternate bridging sequence of trimethylene-ethylene-trimethylene: 2,6,9,13-tetrathiatetradecane (Me(2)-3,2,3-S(4) = L12b) and two cyclohexanediyl-substituted derivatives, viz., cis-1,2-bis[(3-methylthiopropyl)thio]cyclohexane (cis-cyhx-Me(2)-3,2,3-S(4) = L14) and trans-1,2-bis[(3-methylthiopropyl)thio]cyclohexane (trans-cyhx-Me(2)-3,2,3-S(4) = L15). The corresponding phenylene derivative, 1,2-bis[(3-(methylthio)propyl)thio]benzene (bz-Me(2)-3,2,3-S(4) = L13), was also synthesized but did not form a measurable copper complex. The conditional stability constants for Cu(II)L (K(Cu)()II(L)(')) and Cu(I)L (K(Cu)()I(L)(')) and the Cu(II/I)L formal redox potentials (E(f)) vs NHE at 25 degrees C (generally at &mgr; = 0.10 (NaClO(4))) are as follows: for L12b, 15 M(-)(1), 1.0 x 10(13) M(-)(1), 0.83 V; for L14, 2.8 x 10(2) M(-)(1), 0.9(5) x 10(13) M(-)(1), 0.75 V; for L15, 8.8 x 10(2) M(-)(1), 6.(3) x 10(13) M(-)(1), 0.77 V. Application of the Marcus relationship to the experimentally determined cross-reaction rate constants yielded self-exchange rate constants for all four Cu(II/I)L acyclic systems which were relatively constant for both oxidation and reduction under a wide range of conditions. This contrasts sharply with previous results obtained for corresponding macrocyclic ligand systems.

Disentangling the Correlates of Drug Use in a Clinic and Community Sample: A Regression Analysis of the Associations between Drug Use, Years-of-School, Impulsivity, IQ, Working Memory, and Psychiatric Symptoms.

Years-of-school is negatively correlated with illicit drug use. However, educational attainment is positively correlated with IQ and negatively correlated with impulsivity, two traits that are also correlated with drug use. Thus, the negative correlation between education and drug use may reflect the correlates of schooling, not schooling itself. To help disentangle these relations we obtained measures of working memory, simple memory, IQ, disposition (impulsivity and psychiatric status), years-of-school and frequency of illicit and licit drug use in methadone clinic and community drug users. We found strong zero-order correlations between all measures, including IQ, impulsivity, years-of-school, psychiatric symptoms, and drug use. However, multiple regression analyses revealed a different picture. The significant predictors of illicit drug use were gender, involvement in a methadone clinic, and years-of-school. That is, psychiatric symptoms, impulsivity, cognition, and IQ no longer predicted illicit drug use in the multiple regression analyses. Moreover, high risk subjects (low IQ and/or high impulsivity) who spent 14 or more years in school used stimulants and opiates less than did low risk subjects who had spent <14 years in school. Smoking and drinking had a different correlational structure. IQ and years-of-school predicted whether someone ever became a smoker, whereas impulsivity predicted the frequency of drinking bouts, but years-of-school did not. Many subjects reported no use of one or more drugs, resulting in a large number of "zeroes" in the data sets. Cragg's Double-Hurdle regression method proved the best approach for dealing with this problem. To our knowledge, this is the first report to show that years-of-school predicts lower levels of illicit drug use after controlling for IQ and impulsivity. This paper also highlights the advantages of Double-Hurdle regression methods for analyzing the correlates of drug use in community samples.

Myosin-X functions in polarized epithelial cells.

Myosin-X (Myo10) is an unconventional myosin that localizes to the tips of filopodia and has critical functions in filopodia. Although Myo10 has been studied primarily in nonpolarized, fibroblast-like cells, Myo10 is expressed in vivo in many epithelia-rich tissues, such as kidney. In this study, we investigate the localization and functions of Myo10 in polarized epithelial cells, using Madin-Darby canine kidney II cells as a model system. Calcium-switch experiments demonstrate that, during junction assembly, green fluorescent protein-Myo10 localizes to lateral membrane cell-cell contacts and to filopodia-like structures imaged by total internal reflection fluorescence on the basal surface. Knockdown of Myo10 leads to delayed recruitment of E-cadherin and ZO-1 to junctions, as well as a delay in tight junction barrier formation, as indicated by a delay in the development of peak transepithelial electrical resistance (TER). Although Myo10 knockdown cells eventually mature into monolayers with normal TER, these monolayers do exhibit increased paracellular permeability to fluorescent dextrans. Importantly, knockdown of Myo10 leads to mitotic spindle misorientation, and in three-dimensional culture, Myo10 knockdown cysts exhibit defects in lumen formation. Together these results reveal that Myo10 functions in polarized epithelial cells in junction formation, regulation of paracellular permeability, and epithelial morphogenesis.