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The present study examined the association of anxiety and impulsivity with premature muzzle grayness among young dogs. A sample of 400 dogs, ages 1–4 years was obtained at dog parks, shows, veterinary clinics, and other venues. Each dog was photographed and the degree of muzzle grayness was rated on an ordinal scale ranging from “no gray” to “full gray.” White or pale colored dogs were dropped from the study because it was impossible to determine degree of grayness. Each owner filled out a questionnaire assessing the constructs of anxiety and impulsivity, as well as other behaviors and characteristics. To prevent response bias, owners were told that the purpose of the study involved dog lifestyle. Distractor items were added to the survey to prevent the owner from guessing the purpose of the survey. Examples of survey items indicating anxiety included: destruction when left alone; hair loss on vet exam or being in a new place; and cringes/cowers in response to groups of people. Examples of survey items indicating impulsivity included: jumping on people, inability to calm, loss of focus, hyperactivity after exercise. In our sample of young dogs, latent variable regression showed that the extent of muzzle grayness was significantly and positively predicted by anxiety ( p = 0.005) and impulsivity ( p < 0.001). Dog size, spay/neuter status, or medical problems did not predict extent of muzzle grayness. Fear responses to loud noise, unfamiliar animals and people were associated with increased grayness. Ordinal regression analysis showed that muzzle grayness was significantly predicted by fear of loud noises ( p = 0.001), unfamiliar animals ( p = 0.031), and unfamiliar people ( p < 0.001). Premature graying in young dogs may be a possible indicator of anxiety, fear or impulsivity issues in dogs under four years of age. [ABSTRACT FROM AUTHOR]

Abstract: Following the ban in 2003 on the use of tributyl-tin compounds in antifouling coatings, the search for an environmentally-friendly alternative has accelerated. Biocidal TBT alternatives, such as diuron and Irgarol 1051®, 1 [1] Irgarol 1051® — registered trademark no. 2195791, Ciba Specialty Chemicals Corp., US. have proved to be environmentally damaging to marine organisms. The issue regarding the use of biocides is that concerning the half-life of the compounds which allow a perpetuation of the toxic effects into the marine food chain, and initiate changes in the early stages of the organisms' life-cycle. In addition, the break-down of biocides can result in metabolites with greater toxicity and longevity than the parent compound. Functionalized coatings have been designed to repel the settlement and permanent attachment of fouling organisms via modification of either or both surface topography and surface chemistry, or by interfering with the natural mechanisms via which fouling organisms settle upon and adhere to surfaces. A large number of technologies are being developed towards producing new coatings that will be able to resist biofouling over a period of years and thus truly replace biocides as antifouling systems. In addition urgent research is directed towards the exploitation of mechanisms used by living organisms designed to repel the settlement of fouling organisms. These biomimetic strategies include the production of antifouling enzymes and novel surface topography that are incompatible with permanent attachment, for example, by mimicking the microstructure of shark skin. Other research seeks to exploit chemical signals and antimicrobial agents produced by diverse living organisms in the environment to prevent settlement and growth of fouling organisms on vulnerable surfaces. Novel polymer-based technologies may prevent fouling by means of unfavourable surface chemical and physical properties or by concentrating antifouling compounds around surfaces. [Copyright &y& Elsevier]

Abstract: Background: Performance status (PS) is a commonly used factor in determining the appropriateness for chemotherapy of patients with non-small cell lung cancer (NSCLC). The prevalence of poor PS and impact of chemotherapy on survival among NSCLC patients has not been studied in community populations. Patients and methods: Insured patients, aged 50+ years, diagnosed with advanced stage NSCLC between 2000 and 2007 were identified via tumor registry (n =292) and linked to electronic medical records, automated medical claims, and Census tract information. A multivariate Cox proportional hazards model was used to determine the factors associated with survival. Results: Of 292 stage IIIB–IV patients, 82 (28%) had PS 3 or 4, and 39% of PS 3–4 patients received first line chemotherapy. Those who received chemotherapy lived 4.8 months compared to 2.4 months for those who did not. Factors associated with a reduced likelihood of death included receipt of chemotherapy (hazard ratio [HR], 0.64), and female gender (HR, 0.71). Modern chemotherapy may be associated with positive effects on survival for poor PS patients, as for good PS patients. Further trials, especially randomized trials, in this neglected subgroup are indicated. [Copyright &y& Elsevier]

Abstract: Background: Lorazepam (Ativan®), diphenhydramine (Benadryl®), haloperidol (Haldol®) (ABH) topical gel is currently widely used for nausea in hospice because of perceived efficacy and low cost and has been suggested for cancer chemotherapy. However, there are no studies of absorption, a prerequisite for effectiveness. We completed this study to establish whether ABH gel drugs are absorbed, as a prerequisite to effectiveness. Intervention: Ten healthy volunteers, aged 25 to 58 years (mean 37 years), two African Americans and eight Caucasian Americans, applied the standard 1.0mL dose (2mg of lorazepam, 25mg of diphenhydramine, and 2mg of haloperidol in a pluronic lecithin organogel), rubbed on the volar surface of the wrists by the subject. Measures: Blood samples were obtained at 0, 30, 60, 90, 120, 180, and 240 minutes. Plasma concentrations were analyzed by liquid chromatography-tandem mass spectrometry using deuterated internal standards for each drug. Outcomes: No lorazepam or haloperidol was detected in any sample from any of the 10 volunteers down to a level of 0.05ng/mL. Diphenhydramine was found in multiple plasma samples at concentrations >0.05ng/mL in three patients, with the highest concentration of 0.30ng/mL in one person at 240 minutes. Overall, five of 10 patients exhibited detectable diphenhydramine in one or more samples, supporting limited absorption. No subject noted any side effects. Conclusions/Lessons Learned: As commonly used, none of the lorazepam, haloperidol, or diphenhydramine in ABH gel is absorbed in sufficient quantities to be effective in the treatment of nausea and vomiting. Diphenhydramine is erratically absorbed at subtherapeutic levels. The efficacy of ABH gel should be confirmed in randomized trials before its use is recommended. [Copyright &y& Elsevier]

Summary: Background: Evidence-based guidelines recommend chemotherapy for medically fit patients with stages II–IV non-small cell lung cancer (NSCLC). Adherence to chemotherapy guidelines has rarely been studied among large populations, mainly because performance status (PS), a key component in assessing chemotherapy appropriateness, is missing from claims-based datasets. Among a large cohort of patients with known PS, we describe first line chemotherapy use relative to guideline recommendations and identify patient factors associated with guideline concordant use. Patients and methods: Insured patients, ages 50+, with stages II–IV NSCLC between 2000 and 2007 were identified via tumor registry (n =406). Chart abstracted PS, automated medical claims, Census tract information, and travel distance were linked to tumor registry data. Chemotherapy was considered appropriate for patients with PS 0–2. Multivariate logit models were fit to evaluate patient characteristics associated with chemotherapy over- and under-use per guideline recommendations. Tests of statistical significance were two sided. Results: Overall compliance with first line chemotherapy guidelines was 71%. Significant (p <0.05) predictors of chemotherapy underuse (19%) included increasing age (odds ratio [OR], 1.09), higher income (OR, 1.02), diagnosed before 2003 (OR, 2.05), and vehicle access (OR, 6.96) in the patient''s neighborhood. Significant predictors of chemotherapy overuse (10%) included decreasing age (OR, 0.92), diagnosed after 2003 (OR, 3.24), and higher income (OR, 1.05) in the patient''s neighborhood. Among NSCLC patients 29% do not receive guideline recommended chemotherapy treatment missing opportunities for cure or beneficial palliation, or receiving chemotherapy with more risk of harm than benefit. Care concordant with guidelines is influenced by age, economic considerations such as income and transportation barriers. [ABSTRACT FROM AUTHOR]

Abstract: Context: Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting and persistent consequence of numerous classes of antineoplastic agents, affecting up to 30%–40% of patients. To date, there is no effective prevention or therapy. An evolving hypothesis for reducing CIPN pain involves direct nerve stimulation to reduce the pain impulse. Objectives: To evaluate the impact on CIPN associated with the MC5-A Calmare® therapy device. Methods: The MC5-A Calmare® therapy device is designed to generate a patient-specific cutaneous electrostimulation to reduce the abnormal pain intensity. Sixteen patients from one center received one-hour interventions daily over 10 working days. Results: Of 18 patients, 16 were evaluable. The mean age of the patients was 58.6 years—four men and 14 women—and the duration of CIPN was three months to eight years. The most common drugs were taxanes, platinums, and bortezomib (Velcade, Millenium Pharmaceuticals, Cambridge MA). At the end of the study (Day 10), a 20% reduction in numeric pain scores was achieved in 15 of 16 patients. The pain score fell 59% from 5.81±1.11 before treatment to 2.38±1.82 at the end of 10 days (P <0.0001 by paired t-test). A daily treatment benefit was seen with a strong statistically significant difference between the pre- and post-daily pain scores (P <0.001). Four patients had their CIPN reduced to zero. A repeated-measures analysis using the scores from all 10 days confirmed these results. No toxicity was seen. Some responses have been durable without maintenance. Conclusion: Patient-specific cutaneous electrostimulation with the MC5-A Calmare® device appears to dramatically reduce pain in refractory CIPN patients with no toxicity. Further studies are underway to define the benefit, mechanisms of action, and optimal schedule. [ABSTRACT FROM AUTHOR]

Abstract: Nucleoside derivatives are a class of compounds that have attracted intense interest in biotechnology and medicine. Use of biocatalysts opens exciting opportunities for selective synthesis of many nucleoside derivatives, and such an approach offers simplicity, exquisite selectivity and environmentally benign processes. Here we reviewed current achievements in the biocatalytic transformation of nucleoside derivatives from the literature between 2000 and 2009. This article is arranged according to the types of reactions that can be employed to transform nucleoside derivatives, which include acylation, deacylation, glycosylation, halogenation and deamination. [Copyright &y& Elsevier]

Summary: SusG is an α-amylase and part of a large protein complex on the outer surface of the bacterial cell and plays a major role in carbohydrate acquisition by the animal gut microbiota. Presented here, the atomic structure of SusG has an unusual extended, bilobed structure composed of amylase at one end and an unprecedented internal carbohydrate-binding motif at the other. Structural studies further demonstrate that the carbohydrate-binding motif binds maltooligosaccharide distal to, and on the opposite side of, the amylase catalytic site. SusG has an additional starch-binding site on the amylase domain immediately adjacent to the active cleft. Mutagenesis analysis demonstrates that these two additional starch-binding sites appear to play a role in catabolism of insoluble starch. However, elimination of these sites has only a limited effect, suggesting that they may have a more important role in product exchange with other Sus components. [Copyright &y& Elsevier]

Objective: To develop an instrument to assess client-centered counseling behaviors (skills) of student-counselors in a standardized patient (SP) exercise. Methods: Descriptive study of the accuracy and utility of a newly developed counseling evaluation instrument. Study participants included 11 female student-counselors at a Midwestern university-10 Caucasian, 1 African-American-for the simulated counseling sessions, in which the Feedback on Counseling Using Simulation (FOCUS) instrument was applied in 2 SP scenarios (cardiovascular disease and diabetes). FOCUS ratings of student-counselors by 4 SPs during 22 sessions were compared with ratings from a 3-member panel of experts who independently viewed the 22 videotaped sessions. Quantitative analysis of instrument validity included inter-rater reliability by computing generalizability coefficients, Pearson correlations, and Spearman rank-order correlations. Results: FOCUS criteria encompassed relevant dimensions of nutrition counseling based in a client-centered perspective. The critical points of information gathering and counseling behaviors showed internal consistency overall and good inter-rater reliability with the cardiovascular disease scenario. For both scenarios, pooled ratings of 3 experts agreed with ratings carried out by SPs. Conclusions and Implications: Initial findings suggest that the FOCUS instrument with client-centered criteria may enhance evaluation of counseling skills in SP exercises, meriting further study with larger groups. [ABSTRACT FROM AUTHOR]

Abstract: Although palliative care is rarely profitable by itself, palliative care in hospitals is associated with significant reductions in per diem costs and total costs, and can generate substantial savings to the health system by “cost avoidance.” Palliative care alongside usual care in recent randomized outpatient trials has maintained or improved the quality of care while generating substantial cost savings. The data are mixed about the impact of palliative care consultation on inpatient length of stay and are related to local patterns of care, consultation, and assumption of control of the course of care. In collecting and presenting the data to administrators and others, we have found that the simplest approach is the most effective—for example, presenting a few clinical outcomes alongside cost-saving data. [Copyright &y& Elsevier]

Glutamate dehydrogenase (GDH) is found in all living organisms, but only animal GDH is regulated by a large repertoire of metabolites. More than 50 years of research to better understand the mechanism and role of this allosteric network has been frustrated by its sheer complexity. However, recent studies have begun to tease out how and why this complex behavior evolved. Much of GDH regulation probably occurs by controlling a complex ballet of motion necessary for catalytic turnover and has evolved concomitantly with a long antenna-like feature of the structure of the enzyme. Ciliates, the ‘missing link’ in GDH evolution, might have created the antenna to accommodate changing organelle functions and was refined in humans to, at least in part, link amino acid catabolism with insulin secretion. [Copyright &y& Elsevier]

Abstract: 1,3-Butadiene (BD) is metabolized in humans and rodents to mutagenic and carcinogenic species. Our previous work has focused on developing a physiologically based toxicokinetic (PBTK) model for BD to estimate its metabolic rate to 1,2-epoxy-3-butene (EB), using exhaled breath BD concentrations in human volunteers exposed by inhalation. In this paper, we extend our BD model to describe the kinetics of its four major metabolites EB, 1,2:3,4-diepoxybutane (DEB), 3-butene-1,2-diol (BDD), and 3,4-epoxy-1,2-butanediol (EBD), and to test whether the extended model and experimental data (to be collected for BD and metabolites in humans) are together adequate to estimate the metabolic rate constants of each of the above chemicals. Global sensitivity analyses (GSA) were conducted to evaluate the relative importance of the model parameters on model outputs during the 20min of exposure and the 40min after exposure ended. All model parameters were studied together with various potentially measurable model outputs: concentrations of BD and EB in exhaled air, concentrations of BD and all metabolites in venous blood, and cumulated amounts of urinary metabolites excreted within 24h. Our results show that pulmonary absorption of BD and subsequent distribution and metabolism in the well-perfused tissues compartment are the critical processes in the toxicokinetics of BD and metabolites. In particular, three parameters influence numerous outputs: the blood:air partition coefficient for BD, the metabolic rate of BD to EB, and the volume of the well-perfused tissues. Other influential parameters include other metabolic rates, some partition coefficients, and parameters driving the gas exchanges (in particular, for BD outputs). GSA shows that the impact of the metabolic rate of BD to EB on the BD concentrations in exhaled air is greatly increased if a few of the model''s important parameters (such as the blood:air partition coefficient for BD) are measured experimentally. GSA also shows that all the transformation pathways described in the PBTK model may not be estimable if only data on the studied outputs are collected, and that data on a specific output for a chemical may not inform all the transformations involving that chemical. [Copyright &y& Elsevier]

Abstract: This study analyzed the workplace area concentrations and the personal exposure concentrations to fine particulate (PM2.5), elemental carbon (EC), and organic carbon (OC) measured during the winter period in trucking companies. The averaged personal exposure concentrations at breathing zones of workers are much greater than those of the microenvironment concentrations. The highest difference between the area (microenvironment) and personal exposure concentrations was in the PM2.5 concentrations followed by the OC concentrations. The area concentrations of PM2.5, EC, and OC at a large terminal were higher than those at a small one. The highest area concentrations of PM2.5, EC, and OC were observed in the shop areas followed by pick-up and delivery (P&D) areas. The area concentrations and personal exposure to PM2.5, EC, and OC in the shop and P&D areas which are highly affected by diesel engine exhaust emissions were much higher than those in the docks which are significantly affected by liquefied petroleum gas (LPG) engine exhaust emissions. The highest EC fraction to the total carbon (EC+OC) concentrations was observed in the shops, while the lowest one was identified in the offices. The personal exposure of the smoking workers to PM2.5 and OC was much higher than that of the non-smoking workers. However, the smoking might not significantly contribute to the personal exposure to EC. There were significant correlations between the PM2.5 and OC concentrations in both the area and personal exposure concentrations. However, significant correlations between the PM2.5 and EC concentrations and between the OC and EC concentrations were not identified. [Copyright &y& Elsevier]

• Students' sense of school belonging positively predicts liking of science. • Students' sense of school belonging positively predicts valuing of science. • In Portugal, effect of school belonging on liking/valuing science differs by gender. This study used the Trends in International Math Science (TIMSS) 2015 Advanced data from nine countries to examine the relationship between students' sense of school belonging and their attitudes towards mathematics, and the extent to which student gender moderated these relationships. Results showed that students' sense of school belonging emerged as a statistically significant, positive predictor of students' liking and valuing of mathematics. For most countries, no significant moderating effect of student gender was observed. However, among Portuguese students, the relationship between students' sense of school belonging and each attitude measure was stronger for males than for females. [ABSTRACT FROM AUTHOR]

Using a stigma-based bullying framework, the current study investigated how (a) disability status was related to bullying-related behaviors when controlling for gender, grade level, and free or reduced lunch status; (b) gender, grade level, and free or reduced lunch status moderated the associations of disability status with bullying-related behaviors; and (c) classification in specific disability categories was associated with bullying-related behaviors with a sample of 10,483 students (47.8% female) in elementary, middle, and high school. School records data were collected on grade level, gender, free or reduced lunch price status, disability status, and disability category. Students completed the Bullying Participant Behaviors Questionnaire (BPBQ), rating five types of bully role behaviors (bullying behavior, assistant behavior, victimization, defending behavior, and outsider behavior). Findings indicated that having a disability was associated with increased victimization, assisting, and defending behavior. Furthermore, disability status interacted in meaningful ways with several demographic factors: (a) females with a disability reported more victimization and reported engaging in more outsider behaviors than females without a disability, (b) elementary students with a disability reported more assisting and less defending behaviors than those without a disability, (c) high school students with a disability reported less bullying and assisting behaviors and more defending behaviors than those without a disability, and (d) students with a disability from low socioeconomic backgrounds reported more bullying and outsider behaviors than students not from lower socioeconomic family backgrounds. When comparing students from specific disability categories to those with no disability, students with an emotional disability reported more assisting, victimization, and outsider behaviors; students with other health impairment reported more assisting, victimization, and defending; students with autism reported less defending and outsider behaviors; and students with a learning disability reported more defending behavior. Exploratory analyses of the effects of school-level factors found that school size (enrollment) was positively related to prevalence of assisting and outsider behavior. The percentage of low-income students in a school was positively associated with the extent of victimization and defending behaviors reported, but negatively associated with the extent of outsider behaviors reported. [ABSTRACT FROM AUTHOR]

Palliative care offers patient and family centered approaches that may mitigate risk of caregiver burden and poor mood. To determine whether a palliative care intervention (CONNECT) improved burden, mood, and self-efficacy among caregivers of patients with advanced cancer. In this cluster randomized trial, patients and their caregivers were recruited from 17 Oncology clinics in Pennsylvania. Participants attended nurse-led monthly visits, addressing patient symptoms, goals of care, and advance care planning. At baseline and three months, we measured caregiver burden using Zarit Burden Interview (ZBI-12; range 0–48), caregiver anxiety and depression using Hospital Anxiety and Depression Scales (HADS-A, range 0–21; HADS-D, range 0–21). We measured caregiver self-efficacy at three months using Caregiver Inventory (CGI; range 0–189). We enrolled 441 caregivers and 381 completed three-month assessments. We found no significant differences in caregiver burden (adjusted mean difference -0.39; 95% CI -1.07–0.29, P = 0.90), depression (adjusted mean difference -0.22, 95% CI -0.97–0.55, P = 0.26), or anxiety (adjusted mean difference 0.09; 95% CI -1.25–1.43, P = 0.58), between the intervention and standard care at three months. Caregiver self-efficacy was higher at three months in the intervention compared to standard care (adjusted mean difference 9.36; 95% CI 0.95–17.77, P = 0.030). Caregivers in CONNECT did not experience improved burden or mood, however, they reported higher self-efficacy compared to caregivers receiving standard care. This study highlights the need for strategies to optimize caregiver outcomes in palliative care interventions. [ABSTRACT FROM AUTHOR]

Background: Hospice is underutilized, with over 25% of enrolled patients receiving hospice care for 3 days or less. The inner city emergency department (ED) is a highly trafficked area for patients in the last 6 months of life, and is a potential location for identification of hospice-eligible patients and early palliative care (PC) intervention.Objectives: We evaluated the feasibility of an ED PC intervention to identify hospice-eligible patients to accelerate PC consultation and hospice enrollment.Methods: This prospective, pilot study established a program in the ED via education and a direct line of communication between the ED and PC to identify hospice-eligible patients, with the goal of facilitating disposition to hospice within 24 h. Data were analyzed for time to PC consultation, length of stay, emergency physician (EP) appropriateness of referral, and time from hospitalization to mortality.Results: In a 6-month period, EPs identified 88 hospice-eligible patients with 91% accuracy. Of the patients identified, 59% died within 3 months of their visit to the ED. Time to PC consultation was 2.3 days (SD 2.3), and 57% of those seen by PC were discharged to hospice, vs. 30% of those not consulted (p = 0.038). The potential median hospice length of stay was 31.5 days, better than for the institution as a whole.Conclusions: Our pilot study presents a unique approach to early identification and disposition of hospice-appropriate patients, and suggests EPs may have sufficient prognostic accuracy to perform this task. [ABSTRACT FROM AUTHOR]

Summary: Cancer costs continue to increase alarmingly despite much debate about how they can be reduced. The oncology community needs to take greater responsibility for our own practice patterns, especially when using expensive tests and treatments with marginal value: we cannot continue to accept novel therapeutics with very small benefits for exorbitant prices. Patients, payers, and pharmaceutical communities should be constructively engaged to communicate medically and economically possible goals, and eventually, to reduce use and costs. Diagnostic tests and treatments should have to show true value to be added to existing protocols. In this article, we discuss three key drivers of costs: end-of-life care patterns, medical imaging, and drugs. We propose health-care models that have the potential to decrease costs and discuss solutions to maintain clinical benefit at an affordable price. [Copyright &y& Elsevier]

Soluble methane monooxygenase (sMMO) is a bacterial multicomponent enzyme that oxidizes a diverse range of substrates, including aromatic hydrocarbons. We have investigated enzyme–substrate interactions that govern oxidation regioselectivity at various sites of aromatic compounds using substrate docking and molecular dynamics (MD) simulations. Here, we studied the hydroxylation of toluene and ethyl benzene by two forms of Methylosinus trichosporium OB3b (sMMO), that is, wild-type (WT) and two active site mutants (L110Y/G). The two substrates, toluene and ethyl benzene, were docked into the active site of the WT and the L110Y/G mutant models of M. trichosporium OB3b sMMO using the available X-ray structure (PDB id 1MHZ ). The trends observed in the formation of the experimental product were highly correlated with the results obtained from the relatively short MD simulation. These results show that our approach could be an attractive computational tool to rationalize the prediction of product ratios and specificities. [ABSTRACT FROM AUTHOR]

Human monoclonal antibodies (m Abs) based on Ig G and Ig A have shown promise as topical microbicide candidates to protect women from HIV infection. Application of mAbs has been limited, however, by the inability of vaginal gels and conventional intravaginal ring ( IVR) designs, the predominant vaginal product formulations, to effectively deliver biomolecules in a coitally independent fashion with retention of bioactivity. We have developed a novel pod- IVR platform that delivers ovine Ig G (ov- Ig G) as a model for Ig G and Ig A human mAbs. In vitro release of ov- Ig G from the pod- IVRs was sustained for 14 days. Facile control of release rate was achieved by changing the size of delivery channels in the ring structure, and the feasibility of ov- Ig G delivery in the range 0.5-30 mg day−1 from a 10-pod IVR was demonstrated. The activity of ov- Ig G in pod- IVR formulations was maintained as confirmed by ELISA binding assay. Pod- IVRs delivering ov- Ig G show promise for the effective sustained topical delivery of antibody-based microbicides. This significantly broadens the range of microbicides that can be delivered in a sustained fashion from IVRs and enables a new arsenal of topical biologic microbicide candidates beyond small molecule antiretrovirals. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:3611-3620, 2014 [ABSTRACT FROM AUTHOR]

Context: Preliminary trials report that Scrambler Therapy, a form of electroanalgesia, may improve discomfort from chemotherapy-induced peripheral neuropathy (CIPN).Objective: The objective of this phase II, randomized controlled trial was to evaluate the efficacy of Scrambler therapy vs. transcutaneous electrical nerve stimulation (TENS) in treating CIPN.Methods: Fifty patients were accrued for the first half of this two-part, crossover trial consisting of a 2-week treatment period with either Scrambler or TENS, followed by an 8-week observation period, and then crossover treatment. Twenty-two patients proceeded to the crossover phase. The primary means of assessment was patient-reported outcomes, including symptom severity scales and Global Impression of Change questionnaires. Symptoms were assessed daily during the treatment period and weekly during an 8-week observation period.Results: A 50% or greater reduction in primary symptom (pain or tingling) score on the last day of treatment was achieved by 6 of 10 Scrambler-treated patients (60%) and 3 of 12 TENS-treated patients (25%) after crossover (P = 0.11). By day 4 of treatment, the two arms diverged with respect to mean change in primary symptom score; this effect was largely carried through to the end of the two-week treatment period. Similarly, Scrambler therapy appeared better than TENS when assessed by Global Impression of Change for neuropathy, pain, and overall quality of life.Conclusions: Similar findings from the initial randomization and crossover phases of this study support further evaluation of the efficacy of Scrambler therapy in alleviating CIPN symptoms. Evaluation in a larger, randomized controlled trial with standardized treatment is warranted. [ABSTRACT FROM AUTHOR]

Abstract: The goal of this investigation was to examine how sediment accretion and organic carbon (OC) burial rates in mangrove forests respond to climate change. Specifically, will the accretion rates keep pace with sea-level rise, and what is the source and fate of OC in the system? Mass accumulation, accretion and OC burial rates were determined via 210Pb dating (i.e. 100year time scale) on sediment cores collected from two mangrove forest sites within Everglades National Park, Florida (USA). Enhanced mass accumulation, accretion and OC burial rates were found in an upper layer that corresponded to a well-documented storm surge deposit. Accretion rates were 5.9 and 6.5mmyr−1 within the storm deposit compared to overall rates of 2.5 and 3.6mmyr−1. These rates were found to be matching or exceeding average sea-level rise reported for Key West, Florida. Organic carbon burial rates were 260 and 393gm−2 yr−1 within the storm deposit compared to 151 and 168gm−2 yr−1 overall burial rates. The overall rates are similar to global estimates for OC burial in marine wetlands. With tropical storms being a frequent occurrence in this region the resulting storm surge deposits are an important mechanism for maintaining both overall accretion and OC burial rates. Enhanced OC burial rates within the storm deposit could be due to an increase in productivity created from higher concentrations of phosphorus within storm-delivered sediments and/or from the deposition of allochthonous OC. Climate change-amplified storms and sea-level rise could damage mangrove forests, exposing previously buried OC to oxidation and contribute to increasing atmospheric CO2 concentrations. However, the processes described here provide a mechanism whereby oxidation of OC would be limited and the overall OC reservoir maintained within the mangrove forest sediments. [Copyright &y& Elsevier]

Abstract: Eddy covariance (EC) estimates of carbon dioxide (CO2) fluxes and energy balance are examined to investigate the functional responses of a mature mangrove forest to a disturbance generated by Hurricane Wilma on October 24, 2005 in the Florida Everglades. At the EC site, high winds from the hurricane caused nearly 100% defoliation in the upper canopy and widespread tree mortality. Soil temperatures down to −50cm increased, and air temperature lapse rates within the forest canopy switched from statically stable to statically unstable conditions following the disturbance. Unstable conditions allowed more efficient transport of water vapor and CO2 from the surface up to the upper canopy layer. Significant increases in latent heat fluxes (LE) and nighttime net ecosystem exchange (NEE) were also observed and sensible heat fluxes (H) as a proportion of net radiation decreased significantly in response to the disturbance. Many of these impacts persisted through much of the study period through 2009. However, local albedo and MODIS (Moderate Resolution Imaging Spectro-radiometer) data (the Enhanced Vegetation Index) indicated a substantial proportion of active leaf area recovered before the EC measurements began 1year after the storm. Observed changes in the vertical distribution and the degree of clumping in newly emerged leaves may have affected the energy balance. Direct comparisons of daytime NEE values from before the storm and after our measurements resumed did not show substantial or consistent differences that could be attributed to the disturbance. Regression analyses on seasonal time scales were required to differentiate the storm''s impact on monthly average daytime NEE from the changes caused by interannual variability in other environmental drivers. The effects of the storm were apparent on annual time scales, and CO2 uptake remained approximately 250gCm−2 yr−1 lower in 2009 compared to the average annual values measured in 2004–2005. Dry season CO2 uptake was relatively more affected by the disturbance than wet season values. Complex leaf regeneration dynamics on damaged trees during ecosystem recovery are hypothesized to lead to the variable dry versus wet season impacts on daytime NEE. In contrast, nighttime CO2 release (i.e., nighttime respiration) was consistently and significantly greater, possibly as a result of the enhanced decomposition of litter and coarse woody debris generated by the storm, and this effect was most apparent in the wet seasons compared to the dry seasons. The largest pre- and post-storm differences in NEE coincided roughly with the delayed peak in cumulative mortality of stems in 2007–2008. Across the hurricane-impacted region, cumulative tree mortality rates were also closely correlated with declines in peat surface elevation. Mangrove forest–atmosphere interactions are interpreted with respect to the damage and recovery of stand dynamics and soil accretion processes following the hurricane. [Copyright &y& Elsevier]

The opium poppy (Papaver somniferum L.) is one of the oldest known medicinal plants. In the biosynthetic pathway for morphine and codeine, salutaridine is reduced to salutaridinol by salutaridine reductase (SalR; EC 1.1.1.248) using NADPH as coenzyme. Here, we report the atomic structure of SalR to a resolution of ~1.9 Å in the presence of NADPH. The core structure is highly homologous to other members of the short chain dehydrogenase/reductase family. The major difference is that the nicotinamide moiety and the substrate-binding pocket are covered by a loop (residues 265-279), on top of which lies a large "flap"-like domain (residues 105-140). This configuration appears to be a combination of the two common structural themes found in other members of the short chain dehydrogenase/reductase family. Previous modeling studies suggested that substrate inhibition is due to mutually exclusive productive and nonproductive modes of substrate binding in the active site. This model was tested via site-directed mutagenesis, and a number of these mutations abrogated substrate inhibition. However, the atomic structure of SalR shows that these mutated residues are instead distributed over a wide area of the enzyme, and many are not in the active site. To explain how residues distal to the active site might affect catalysis, a model is presented whereby SalR may undergo significant conformational changes during catalytic turnover. [ABSTRACT FROM AUTHOR]

Trillions of microbes inhabit the distal gut of adult humans. They have evolved to compete efficiently for nutrients, including a wide array of chemically diverse, complex glycans present in our diets, secreted by our intestinal mucosa, and displayed on the surfaces of other gut microbes. Here, we review how members of the Bacteroidetes, one of two dominant gut-associated bacterial phyla, process complex glycans using a series of similarly patterned, cell envelope-associated multiprotein systems. These systems provide insights into how gut, as well as terrestrial and aquatic, Bacteroidetes survive in highly competitive ecosystems. [ABSTRACT FROM AUTHOR]

Intracortical microelectrode arrays (MEAs) are used to record neural activity. However, their implantation initiates a neuroinflammatory cascade, involving the accumulation of reactive oxygen species, leading to interface failure. Here, we coated commercially-available MEAs with Mn(III)tetrakis(4-benzoic acid)porphyrin (MnTBAP), to mitigate oxidative stress. First, we assessed the in vitro cytotoxicity of modified sample substrates. Then, we implanted 36 rats with uncoated, MnTBAP-coated ("Coated"), or (3-Aminopropyl)triethoxysilane (APTES)-coated devices – an intermediate step in the coating process. We assessed electrode performance during the acute (1–5 weeks), sub-chronic (6–11 weeks), and chronic (12–16 weeks) phases after implantation. Three subsets of animals were euthanized at different time points to assess the acute, sub-chronic and chronic immunohistological responses. Results showed that MnTBAP coatings were not cytotoxic in vitro, and their implantation in vivo improved the proportion of electrodes during the sub-chronic and chronic phases; APTES coatings resulted in failure of the neural interface during the chronic phase. In addition, MnTBAP coatings improved the quality of the signal throughout the study and reduced the neuroinflammatory response around the implant as early as two weeks, an effect that remained consistent for months post-implantation. Together, these results suggest that MnTBAP coatings are a potentially useful modification to improve MEA reliability. [Display omitted] • Mn(III)tetrakis(4- benzoic acid)porphyrin (MnTBAP) was not found to be cytotoxic in vitro. • The MnTBAP coatings on microelectrode arrays (MEAs) improved recording quality and electrode performance. • The MnTBAP coatings reduced neuroinflammation around MEAs. [ABSTRACT FROM AUTHOR]

Dyspnea, a subjective symptom of impaired breathing, occurs in 70% of terminally ill cancer patients. Current treatments are suboptimal and little is known about the patient''s perception of effect. We tested nebulized inhaled fentanyl citrate on patient perceptions, respiratory rate, and oxygen saturation. The study was conducted using a convenience sample of 35 cancer patients on a dedicated oncology unit. We assessed patient perception (did breathing stay the same, worsen, or improve), respiratory rate, and oxygen saturation by pulse oximetry at baseline, 5 minutes, and 60 minutes. Twenty-six of 32 (81%) patients reported improvement in breathing, 3 (9%) were unsure, and 3 (9%) reported no improvement. Oxygen saturation improved from 94.6% at baseline to 96.8% at 5 minutes and 96.7% at 60 minutes (P = 0.0069 compared to baseline). Respiratory rates improved from a baseline of 28.4/min to 25.9/min at 5 minutes and 24.1/min at 60 minutes (P = 0.0251 compared to baseline). No side effects were observed. Inhaled nebulized fentanyl citrate significantly improved patient perception of breathing, respiratory rate, and oxygen saturation. This inexpensive and readily available treatment may offer substantial relief of end-of-life dyspnea. Randomized trials, dose, and length of effect trials are underway. [Copyright &y& Elsevier]

Purpose: To determine whether a machine learning approach optimizes survival estimation for patients with symptomatic bone metastases (SBM), we developed the Bone Metastases Ensemble Trees for Survival (BMETS) to predict survival using 27 prognostic covariates. To establish its relative clinical utility, we compared BMETS with 2 simpler Cox regression models used in this setting.Methods and Materials: For 492 bone sites in 397 patients evaluated for palliative radiation therapy (RT) for SBM from January 2007 to January 2013, data for 27 clinical variables were collected. These covariates and the primary outcome of time from consultation to death were used to build BMETS using random survival forests. We then performed Cox regressions as per 2 validated models: Chow's 3-item (C-3) and Westhoff's 2-item (W-2) tools. Model performance was assessed using cross-validation procedures and measured by time-dependent area under the curve (tAUC) for all 3 models. For temporal validation, a separate data set comprised of 104 bone sites treated in 85 patients in 2018 was used to estimate tAUC from BMETS.Results: Median survival was 6.4 months. Variable importance was greatest for performance status, blood cell counts, recent systemic therapy type, and receipt of concurrent nonbone palliative RT. tAUC at 3, 6, and 12 months was 0.83, 0.81, and 0.81, respectively, suggesting excellent discrimination of BMETS across postconsultation time points. BMETS outperformed simpler models at each time, with respective tAUC at each time of 0.78, 0.76, and 0.74 for the C-3 model and 0.80, 0.78, and 0.77 for the W-2 model. For the temporal validation set, respective tAUC was similarly high at 0.86, 0.82, and 0.78.Conclusions: For patients with SBM, BMETS improved survival predictions versus simpler traditional models. Model performance was maintained when applied to a temporal validation set. To facilitate clinical use, we developed a web platform for data entry and display of BMETS-predicted survival probabilities. [ABSTRACT FROM AUTHOR]

Context: Opportunities for the use of palliative care services are missed in African American (AA) communities, despite Level I evidence demonstrating their benefits.Objectives: Single-institution and stakeholder-engaged study to design an intervention to increase palliative care use in AA communities.Methods: Two-phased qualitative research design guided by the Behavior Change Wheel and Theoretical Domains Framework models. In Phase 1, focus group sessions were conducted to identify barriers and facilitators of palliative care use and the viability of community health workers (CHWs) as a solution. After applying the Behavior Change Wheel and Theoretical Domains Framework to data gathered from Phase 1, Phase 2 consisted of a stakeholder meeting to select intervention content and prioritize modes of delivery.Results: A total of 15 stakeholders participated in our study. Target behaviors identified were for patients to gain knowledge about benefits of palliative care, physicians to begin palliative care discussions earlier in treatment, and to improve patient-physician interpersonal communication. The intervention was designed to improve patient capability, physician capability, patient motivation, physician motivation, and increase patient opportunities to use palliative care services. Strategies to change patient and physician behaviors were all facilitated by CHWs and included creation and dissemination of brochures about palliative care to patients, empowerment and activation of patients to initiate goals-of-care discussions, outreach to community churches, and expanding patient social support.Conclusion: Use of a theory-based approach to facilitate the implementation of a multi-component strategy provided a comprehensive means of identifying relevant barriers and enablers of CHWs as an agent to increase palliative care use in AA communities. [ABSTRACT FROM AUTHOR]

Purpose: Numerous randomized trials have demonstrated noninferiority of single- versus multiple-fraction palliative radiation therapy (RT) in the management of uncomplicated bone metastases; yet there is neither a clear definition of what constitutes a complicated lesion, nor substantial data regarding the prevalence of such complicating features in clinical practice. Thus, we identify a range of evidence-based operational definitions of complicated symptomatic bone metastases and characterize the frequency of such complicating features at a high-volume, tertiary care center.Methods and Materials: A retrospective review of patients seen in consultation for symptomatic bone metastases between March 1, 2007, and July 31, 2013, at Johns Hopkins Hospital identified patient and disease characteristics. Descriptive statistics characterized the frequency of the following complicating features: prior RT, prior surgery, neuraxis compromise, pathologic fracture, and soft tissue component at the symptomatic site. A range of definitions for complicated bone metastases was evaluated based on combinations of these features. Uni- and multivariable logistic regressions evaluated the odds of complicated bone metastases as a function of site of primary cancer and of the symptomatic target lesion.Results: A total of 686 symptomatic bone metastases in 401 patients were evaluated. Percent of target sites complicated by prior RT was 4.4%, prior surgery was 8.9%, pathologic fracture was 20.6%, neuraxis compromise was 52.0% among spine and medial pelvis sites, and soft tissue component was 38.6%. More than 96 possible definitions of complicated bone metastases were identified. The presence of such complicated lesions ranged from 2.3% to 67.3%, depending on the operational definition used. Odds of a complicated lesion were significantly higher for spine sites and select nonbreast histologies.Conclusions: In this retrospective study, we found complicated symptomatic bone metastases may be present in up to two-thirds of patients. Literature review also demonstrates no clear standard definition of complicated bone metastases, potentially explaining underutilization of single-fraction palliative RT in this setting. [ABSTRACT FROM AUTHOR]

Context: Little attention has been given to social environmental factors associated with advance care planning (ACP) among African Americans or people living with advanced HIV (PLHIV).Objectives: The present study aimed to identify support network factors that affect the likelihood of naming a decision-maker and of talking to family/friends and doctors about ACP among vulnerable PLHIV.Methods: PLHIV were recruited from a large urban HIV clinic. A social support network inventory was used to calculate number of persons available for various types of support. Characteristics of network members were also collected. Multivariable logistic regression models were fit to examine associations between social network factors and ACP discussion, adjusting for age, sex, education, and total number of network members.Results: The sample (N = 370) was mostly African American (95%), male (56%), and 48% had less than a high school education. Almost half the sample (48%) had talked to their family/friends or doctor about ACP, and 34% had named a medical decision-maker. Adjusted analysis revealed that talking about ACP with family/friends was associated with female sex and a larger closer support network who provided health information and physical assistance. Talking to doctors about ACP was associated with larger support networks who provided physical assistance but lower numbers from whom emotional support was received. Naming a decision-maker was associated with greater numbers of network members who provided emotional support, health information, and medication adherence reminders.Conclusion: The findings revealed aspects of family/support network structures and caregiving function associated with ACP in a population with often vital yet vulnerable networks. [ABSTRACT FROM AUTHOR]

Objective: To examine the association between family companion presence during pre-surgical visits to discuss major cancer surgery and patient-provider communication and satisfaction.Methods: Secondary analysis of 61 pre-surgical visit recordings with eight surgical oncologists at an academic tertiary care hospital using the Roter Interaction Analysis System (RIAS). Surgeons, patients, and companions completed post-visit satisfaction questionnaires. Poisson and logistic regression models assessed differences in communication and satisfaction when companions were present vs. absent.Results: There were 46 visits (75%) in which companions were present, and 15 (25%) in which companions were absent. Companion communication was largely emotional and facilitative, as measured by RIAS. Companion presence was associated with more surgeon talk (IRR 1.29, p = 0.006), and medical information-giving (IRR 1.41, p = 0.001). Companion presence was associated with less disclosure of lifestyle/psychosocial topics by patients (IRR 0.55, p = 0.037). In adjusted analyses, companions' presence was associated with lower levels of patient-centeredness (IRR 0.77, p 0.004). There were no differences in patient or surgeon satisfaction based on companion presence.Conclusion: Companions' presence during pre-surgical visits was associated with patient-surgeon communication but was not associated with patient or surgeon satisfaction.Practice Implications: Future work is needed to develop interventions to enhance patient-companion-provider interactions in this setting. [ABSTRACT FROM AUTHOR]

Background: Surgical patients increasingly have more comorbidities and are of an older age, complicating surgical decision-making in emergent situations. Little is known about surgeons' perceptions of shared decision-making in these settings.Study Design: Twenty semi-structured interviews were conducted with practicing surgeons at 2 large academic medical centers. Thirteen questions and 2 case vignettes were used to assess perceptions of decision-making, considerations when deciding whether to offer to operate, and communication patterns with patients and families.Results: Thematic analysis revealed 6 major themes: responsibility for the decision to operate, perceived futility, surgeon judgment, surgeon introspection, pressure to operate, and costs of the operation. Perceived futility was universally considered a contraindication to surgical intervention. However, the challenge of defining futility led participants to emphasize the importance of patients' self-determined risk-to-benefit analysis when considering surgical intervention. More experienced surgeons reported greater comfort with communicating to patients that a condition was not amenable to an operation and reserved the right to refuse to operate.Conclusions: Due to external pressures and uncertainty, some providers err on the side of operative intervention, despite suspected futility. Greater experience allows surgeons to withstand external pressures, be confident in their assessments of perceived futility, and guide patients and their families away from additional interventions. [ABSTRACT FROM AUTHOR]

Background The addition of specialty palliative care to standard oncology care improves outcomes for patients with advanced cancer and their caregivers, but many lack access to specialty care services. Primary palliative care—meaning basic palliative care services provided by clinicians who are not palliative care specialists—is an alternative approach that has not been rigorously evaluated. Methods A cluster randomized, controlled trial of the CONNECT (Care management by Oncology Nurses to address supportive care needs) intervention, an oncology nurse-led care management approach to providing primary palliative care for patients with advanced cancer and their family caregivers, is currently underway at 16 oncology practices in Western Pennsylvania. Existing oncology nurses are trained to provide symptom management and emotional support, engage patients and families in advance care planning, and coordinate appropriate care using evidence-based care management strategies. The trial will assess the impact of CONNECT versus standard oncology care on patient quality of life (primary outcome), symptom burden, and mood; caregiver burden and mood; and healthcare resource use. Discussion This trial addresses the need for more accessible models of palliative care by evaluating an intervention led by oncology nurses that can be widely disseminated in community oncology settings. The design confronts potential biases in palliative care research by randomizing at the practice level to avoid contamination, enrolling patients prior to informing them of group allocation, and conducting blinded outcome assessments. By collecting patient, caregiver, and healthcare utilization outcomes, the trial will enable understanding of the full range of a primary palliative care intervention's impact. [ABSTRACT FROM AUTHOR]

Examining and addressing unmet care needs is integral to improving the provision and quality of cancer services. This review explored the prevalence of unmet supportive care needs, and factors associated with unmet need, in adults with advanced cancers (solid and hematological malignancies) and their caregivers. Electronic databases (PubMed, CINAHL, EMBASE) were searched, producing 85 papers representing 81 included studies. People with advanced cancer reported the highest unmet needs in financial, health system and information, psychological, and physical and daily living domains, whereas caregivers reported the highest unmet needs in psychological, and patient care and support domains. Distress, depression, and anxiety were associated with higher unmet needs across all unmet need domains for people with advanced cancer and their caregivers. Substantial heterogeneity in study populations and methods was observed. Findings from this review can inform targeted strategies and interventions to address these unmet needs in people with advanced cancer. [Display omitted] • Distress, depression, and anxiety are associated with unmet needs across domains. • Patients and carers share high unmet psychological needs as most prevalent. • Patients report unmet informational, financial, physical needs as most prevalent. • Carers report high unmet care and support needs of patients as most prevalent. • There was substantial heterogeneity, warranting further research with validated tools. [ABSTRACT FROM AUTHOR]

Specialist palliative care (PC) often embraces a "less is more" philosophy that runs counter to the revenue-centric nature of most health care financing in the U.S. A special business case is needed in which the financial benefits for organizations such as hospitals and payers are aligned with the demonstrable clinical benefits for patients. Based on published studies and our work with PC programs over the past 15 years, we identified 10 principles that together form a business model for specialist PC. These principles are relatively well established for inpatient PC but are only now emerging for community-based PC. Three developments that are key for the latter are the increasing penalties from payers for overutilization of hospital stays, the variety of alternative payment models such as accountable care organizations, which foster a population health management perspective, and payer-provider partnerships that allow for greater access to and funding of community-based PC. [ABSTRACT FROM AUTHOR]

Recent clinical trials have demonstrated that pre-exposure prophylaxis (PrEP) may prevent HIV infection in a significant number of HIV-1 negative individuals in venerable populations; however, trial efficacy has been highly variable, with notable successes and failures. Poor adherence to PrEP regimens has been implicated as a primary factor in determining efficacy of these trials. With the exception of CAPRISA 004 where use of a pericoital tenofovir gel led to a 39% reduction in HIV infection, all successful PrEP regimens to date have used the fumarate salt of the tenofovir disoproxil ester prodrug of tenofovir (TDF) alone or in combination with emtricitabine (FTC). A sustained-release, intravaginal ring (IVR) formulation of TDF holds promise for improving adherence and, thus, increasing the effectiveness of PrEP. Here, a novel IVR delivering TDF with sustained zero-order release characteristics that may be controlled over nearly two orders of magnitude is described. Pod-IVRs containing 1–10 pods delivering TDF at 0.01–10 mg d −1 were fabricated and their release characteristics evaluated in vitro . The pod-IVRs stabilized TDF against hydrolytic degradation both in storage and during in vitro release experiments. Successful translation of the TDF pod-IVR from laboratory evaluation to large-scale clinical trials requires the ability to manufacture the devices at low cost and in high quantity. Methods for manufacturing and scale-up were developed and applied to pilot-scale production of TDF pod-IVRs that maintained the IVR’s release characteristics while significantly decreasing the variability in release rate observed between pod-IVRs. This pod-IVR enables for the first time the dose-ranging clinical studies that are required to optimize topical TDF PrEP in terms of efficacy and safety. [ABSTRACT FROM AUTHOR]

High mutation rates and short replication times lead to rapid evolution in RNA viruses. New tools for high-throughput culture and analysis of viral phenotypes will enable more effective studies of viral evolutionary processes. A water-in-oil drop microfluidic system to study virus–cell interactions at the single event level on a massively parallel scale is described here. Murine norovirus (MNV-1) particles were co-encapsulated with individual RAW 264.7 cells in 65 pL aqueous drops formed by flow focusing in 50 μm microchannels. At low multiplicity of infection (MOI), viral titers increased greatly, reaching a maximum 18 h post-encapsulation. This system was employed to evaluate MNV-1 escape from a neutralizing monoclonal antibody (clone A6.2). Further, the system was validated as a means for testing escape from antibody neutralization using a series of viral point mutants. Finally, the replicative capacity of single viral particles in drops under antibody stress was tested. Under standard conditions, many RNA virus stocks harbor minority populations of genotypic and phenotypic variants, resulting in quasispecies. These data show that when single cells are encapsulated with single viral particles under antibody stress without competition from other virions, the number of resulting infectious particles is nearly equivalent to the number of viral genomes present. These findings suggest that lower fitness virions can infect cells successfully and replicate, indicating that the microfluidics system may serve as an effective tool for isolating mutants that escape evolutionary stressors. [ABSTRACT FROM AUTHOR]

CONTEXT: The topical gel known as 'ABH gel,' comprising lorazepam (Ativan((R))), diphenhydramine (Benadryl((R))), and haloperidol (Haldol((R))), is frequently used to treat nausea because of its perceived efficacy, relatively low cost, and ease of use in the home setting. There are limited scientific data on this medication, however. Recent pilot studies showed no absorption of the active ingredients of the gel, prompting further prospective studies into the cause of the perceived efficacy in the clinical setting. OBJECTIVES: To determine any difference in the effectiveness of ABH gel compared with placebo in cancer patients with nausea. METHODS: A randomized, double-blind, placebo-controlled, crossover, noninferiority clinical trial was developed to test the hypothesis that there is no difference in the effectiveness of ABH gel compared with placebo in cancer patients with nausea. The primary outcome was the difference in nausea score (on a 0-10 scale) at baseline and at 60 minutes in each treatment group. The difference in the ABH gel-treated group compared with placebo was evaluated for noninferiority. Secondary outcomes included the number of vomiting episodes and side effects over time. RESULTS: The mean change in nausea score from baseline to 60 minutes after treatment in the ABH gel group was 1.7 ± 2.05 and 0.9 ± 2.45 for the placebo group (P = 0.42). The placebo group was found to be noninferior to the ABH gel group in reducing the nausea score. ABH gel also did not decrease vomiting events better than placebo (P = 0.34). Only one patient reported any side effects from the treatments in either arm of the study. CONCLUSION: ABH gel in its current formulation should not be used in cancer patients experiencing nausea. [ABSTRACT FROM AUTHOR]

Context The topical gel known as “ABH gel,” comprising lorazepam (Ativan ® ), diphenhydramine (Benadryl ® ), and haloperidol (Haldol ® ), is frequently used to treat nausea because of its perceived efficacy, relatively low cost, and ease of use in the home setting. There are limited scientific data on this medication, however. Recent pilot studies showed no absorption of the active ingredients of the gel, prompting further prospective studies into the cause of the perceived efficacy in the clinical setting. Objectives To determine any difference in the effectiveness of ABH gel compared with placebo in cancer patients with nausea. Methods A randomized, double-blind, placebo-controlled, crossover, noninferiority clinical trial was developed to test the hypothesis that there is no difference in the effectiveness of ABH gel compared with placebo in cancer patients with nausea. The primary outcome was the difference in nausea score (on a 0–10 scale) at baseline and at 60 minutes in each treatment group. The difference in the ABH gel-treated group compared with placebo was evaluated for noninferiority. Secondary outcomes included the number of vomiting episodes and side effects over time. Results The mean change in nausea score from baseline to 60 minutes after treatment in the ABH gel group was 1.7 ± 2.05 and 0.9 ± 2.45 for the placebo group ( P = 0.42). The placebo group was found to be noninferior to the ABH gel group in reducing the nausea score. ABH gel also did not decrease vomiting events better than placebo ( P = 0.34). Only one patient reported any side effects from the treatments in either arm of the study. Conclusion ABH gel in its current formulation should not be used in cancer patients experiencing nausea. [ABSTRACT FROM AUTHOR]

Purpose This study evaluates outcomes and patterns of care among patients receiving radiation therapy (RT) for bone metastases at a high-volume academic institution. Methods and Materials Records of all patients whose final RT course was for bone metastases from April 2007 to July 2012 were identified from electronic medical records. Chart review yielded demographic and clinical data. Rates of complicated versus uncomplicated bone metastases were not analyzed. Results We identified 339 patients whose final RT course was for bone metastases. Of these, 52.2% were male; median age was 65 years old. The most common primary was non-small-cell lung cancer (29%). Most patients (83%) were prescribed ≤10 fractions; 8% received single-fraction RT. Most patients (52%) had a documented goals of care (GOC) discussion with their radiation oncologist; hospice referral rates were higher when patients had such discussions (66% with vs 50% without GOC discussion, P=.004). Median life expectancy after RT was 96 days. Median survival after RT was shorter based on inpatient as opposed to outpatient status at the time of consultation (35 vs 136 days, respectively, P<.001). Hospice referrals occurred for 56% of patients, with a median interval between completion of RT and hospice referral of 29 days and a median hospice stay of 22 days. Conclusions These data document excellent adherence to American Society for Radiation Oncolology Choosing Wisely recommendation to avoid routinely using >10 fractions of palliative RT for bone metastasis. Nonetheless, single-fraction RT remains relatively uncommon. Participating in GOC discussions with a radiation oncologist is associated with higher rates of hospice referral. Inpatient status at consultation is associated with short survival. [ABSTRACT FROM AUTHOR]

Abstract: A comparative study was made of Mung bean epoxide hydrolases-catalyzed asymmetric hydrolysis of styrene oxide to (R)-1-phenyl-1,2-ethanediol in an n-hexane/buffer biphasic system containing various hydrophilic ionic liquids (ILs). Compared to the n-hexane/buffer biphasic system alone, addition of a small amount of hydrophilic ILs reduced the amount of non-enzymatic hydrolysis, and improved the reaction rate by up to 22%. The ILs with cation containing an alkanol group, namely [C2OHMIM][BF4] and [C2OHMIM][TfO], and the choline amino acid ILs [Ch][Arg] and [Ch][Pro] were found to be the most suitable co-solvents for the reaction, owing to their good biocompatibility with the enzyme, which led to high initial rates (0.99–1.25μmol/min) and high product e.e.s (95%). When substrate concentration was around 30mM, where optimal performance was observed with the IL-containing systems, the product e.e. was improved from 90% without ILs to ≥95% in the presence of ILs. [Copyright &y& Elsevier]

Human colonic bacteria are necessary for the digestion of many dietary polysaccharides. The intestinal symbiont Bacteroides thetaiotaomicron uses five outer membrane proteins to bind and degrade starch. Here, we report the x-ray crystallographic structures of SusE and SusF, two outer membrane proteins composed of tandem starch specific carbohydrate-binding modules (CBMs) with no enzymatic activity. Examination of the two CBMs in SusE and three CBMs in SusF reveals subtle differences in the way each binds starch and is reflected in their Kd values for both high molecular weight starch and small maltooligosaccharides. Thus, each site seems to have a unique starch preference that may enable these proteins to interact with different regions of starch or its breakdown products. Proteins similar to SusE and SusF are encoded in many other polysaccharide utilization loci that are possessed by human gut bacteria in the phylum Bacteroidetes. Thus, these proteins are likely to play an important role in carbohydrate metabolism in these abundant symbiotic species. Understanding structural changes that diversify and adapt related proteins in the human gut microbial community will be critical to understanding the detailed mechanistic roles that they perform in the complex digestive ecosystem. [ABSTRACT FROM AUTHOR]

Intravaginal delivery of microbicide combinations is a promising approach for the prevention of sexually transmitted infections, but requires a method of providing simultaneous, independent release of multiple agents into the vaginal compartment. A novel intravaginal ring (IVR) platform has been developed for simultaneous delivery of the reverse-transcriptase inhibitor tenofovir (TFV) and the guanosine analogue antiviral acyclovir (ACV) with independent control of release rate for each drug. The IVR is based on a pod design, with up to 10 individual polymer-coated drug cores embedded in the ring releasing through preformed delivery channels. The release rate from each pod is controlled independently of the others by the drug properties, polymer coating, and size and number of delivery channels. Pseudo-zero-order in vitro release of TFV (144 ± 10 µg day) and ACV (120 ± 19 µg day−1) from an IVR containing both drugs was sustained for 28 days. The mechanical properties of the pod IVR were evaluated and compared with the commercially available Estring® (Pfizer, NY, NY). The pod-IVR design enables the vaginal delivery of multiple microbicides with differing physicochemical properties, and is an attractive approach for the sustained intravaginal delivery of relatively hydrophilic drugs that are difficult to deliver using conventional matrix IVR technology. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:2833-2843, 2012 [ABSTRACT FROM AUTHOR]