Processive kinetics in the three-step lanosterol 14α-demethylation reaction catalyzed by human cytochrome P450 51A1.

Cytochrome P450 (P450, CYP) family 51 enzymes catalyze the 14α-demethylation of sterols, leading to critical products used for membranes and the production of steroids, as well as signaling molecules. In mammals, P450 51 catalyzes the 3-step, 6-electron oxidation of lanosterol to form (4ß,5α)-4,4-dimethyl-cholestra-8,14,24-trien-3-ol (FF-MAS). P450 51A1 can also use 24,25-dihydrolanosterol (a natural substrate in the Kandutsch-Russell cholesterol pathway). 24,25-Dihydrolanosterol and the corresponding P450 51A1 reaction intermediates, the 14α-alcohol and -aldehyde derivatives of dihydrolanosterol, were synthesized to study the kinetic processivity of the overall 14α-demethylation reaction of human P450 51A1. A combination of steady-state kinetic parameters, steady-state binding constants, dissociation rates of P450-sterol complexes, and kinetic modeling of the time course of oxidation of a P450-dihydrolanosterol complex showed that the overall reaction is highly processive, with koff rates of P450 51A1-dihydrolanosterol and the 14α-alcohol and 14α-aldehyde complexes being 1 to 2 orders of magnitude less than the forward rates of competing oxidations. epi-Dihydrolanosterol (the 3α-hydroxy analog) was as efficient as the common 3ß-hydroxy isomer in the binding and formation of dihydro FF-MAS. The common lanosterol contaminant dihydroagnosterol was found to be a substrate of human P450 51A1, with roughly one-half the activity of dihydrolanosterol. Steady-state experiments with 14α-methyl deuterated dihydrolanosterol showed no kinetic isotope effect, indicating that C-14α C-H bond breaking is not rate-limiting in any of the individual steps. The high processivity of this reaction generates higher efficiency and also renders the reaction less sensitive to inhibitors.

Role of Electronic Structure on Nitrate Reduction to Ammonium: A Periodic Journey.

Electrocatalysis is a promising approach to convert waste nitrate to ammonia and help close the nitrogen cycle. This renewably powered ammonia production process sources hydrogen from water (as opposed to methane in the thermal Haber-Bosch process) but requires a delicate balance between a catalyst's activity for the hydrogen evolution reaction (HER) and the nitrate reduction reaction (NO3RR), influencing the Faradaic efficiency (FE) and selectivity to ammonia/ammonium over other nitrogen-containing products. We measure ammonium FEs ranging from 3.6 ± 6.6% (on Ag) to 93.7 ± 0.9% (on Co) across a range of transition metals (TMs; Ti, Fe, Co, Ni, Ni0.68Cu0.32, Cu, and Ag) in buffered neutral media. To better understand these competing reaction kinetics, we develop a microkinetic model that captures the voltage-dependent nitrate rate order and illustrates its origin as competitive adsorption between nitrate and hydrogen adatoms (H*). NO3RR FE can be described via competition for electrons with the HER, decreasing sharply for TMs with a high work function and a correspondingly high HER activity (e.g., Ni). Ammonium selectivity nominally increases as the TM d-band center energy (Ed) approaches and overcomes the Fermi level (EF), but is exceptionally high for Co compared to materials with similar Ed. Density functional theory (DFT) calculations indicate Co maximizes ammonium selectivity via (1) strong nitrite binding enabling subsequent reduction and (2) promotion of nitric oxide dissociation, leading to selective reduction of the nitrogen adatom (N*) to ammonium.

Selecting, refining and identifying priority Cochrane Reviews in health communication and participation in partnership with consumers and other stakeholders.

BACKGROUND: Priority-setting partnerships between researchers and stakeholders (meaning consumers, health professionals and health decision-makers) may improve research relevance and value. The Cochrane Consumers and Communication Group (CCCG) publishes systematic reviews in 'health communication and participation', which includes concepts such as shared decision-making, patient-centred care and health literacy. We aimed to select and refine priority topics for systematic reviews in health communication and participation, and use these to identify five priority CCCG Cochrane Reviews. METHODS: Twenty-eight participants (14 consumers, 14 health professionals/decision-makers) attended a 1-day workshop in Australia. Using large-group activities and voting, participants discussed, revised and then selected 12 priority topics from a list of 21 previously identified topics. In mixed small groups, participants refined these topics, exploring underlying problems, who they affect and potential solutions. Thematic analysis identified cross-cutting themes, in addition to key populations and potential interventions for future Cochrane Reviews. We mapped these against CCCG's existing review portfolio to identify five priority reviews. RESULTS: Priority topics included poor understanding and implementation of patient-centred care by health services, the fact that health information can be a low priority for health professionals, communication and coordination breakdowns in health services, and inadequate consumer involvement in health service design. The four themes underpinning the topics were culture and organisational structures, health professional attitudes and assumptions, inconsistent experiences of care, and lack of shared understanding in the sector. Key populations for future reviews were described in terms of social health characteristics (e.g. people from indigenous or culturally and linguistically diverse backgrounds, elderly people, and people experiencing socioeconomic disadvantage) more than individual health characteristics. Potential interventions included health professional education, interventions to change health service/health professional culture and attitudes, and health service policies and standards. The resulting five priority Cochrane Reviews identified were improving end-of-life care communication, patient/family involvement in patient safety, improving future doctors' communication skills, consumer engagement strategies, and promoting patient-centred care. CONCLUSIONS: Stakeholders identified priority topics for systematic reviews associated with structural and cultural challenges underlying health communication and participation, and were concerned that issues of equity be addressed. Priority-setting with stakeholders presents opportunities and challenges for review producers.

Acute Effects of Interrupting Prolonged Sitting With Intermittent Physical Activity on Blood Pressure in Preadolescent Children.

PURPOSE: To compare the acute effects of intermittent physical activity (PA) across 4 different intensities on blood pressure. METHODS: Thirty children (12 males and 18 females; aged 7-11 y; 33% overweight/obese; 53% nonwhite) completed 4 experimental conditions in random order: 8 hours sitting interrupted with 20, 2-minute low-, moderate-, high-intensity PA breaks, or sedentary screen-time breaks. PA intensity corresponded with 25%, 50%, and 75% of heart rate reserve. Blood pressure was measured during each condition in the morning (0800 h), noon (1200 h), and afternoon (1600 h). RESULTS: There were no significant differences across conditions for systolic blood pressure (SBP; all Ps > .05). There was a significant effect of time with SBP decreasing throughout the day for all conditions (average morning SBP: 106 [1] mm Hg, average noon SBP: 101 [2] mm Hg, average afternoon SBP: 103 [1] mm Hg; P = .01). There were no significant effects of condition or time on diastolic blood pressure (all Ps > .05). CONCLUSION: While sedentary behavior is known to be associated with hypertension in both adults and children, a single bout of prolonged sitting may be insufficient to produce hypertensive effects in otherwise healthy children. Future research should examine the appropriate dose of intermittent PA to accrue hypotensive responses in preadolescent children.

Effect of Fluoxetine on Obsessive-Compulsive Behaviors in Children and Adolescents With Autism Spectrum Disorders: A Randomized Clinical Trial.

Importance: Selective serotonin receptor inhibitors are prescribed to reduce the severity of core behaviors of autism spectrum disorders, but their efficacy remains uncertain. Objective: To determine the efficacy of fluoxetine for reducing the frequency and severity of obsessive-compulsive behaviors in autism spectrum disorders. Design, Setting, and Participants: Multicenter, randomized, placebo-controlled clinical trial. Participants aged 7.5-18 years with autism spectrum disorders and a total score of 6 or higher on the Children's Yale-Brown Obsessive Compulsive Scale, modified for pervasive developmental disorder (CYBOCS-PDD) were recruited from 3 tertiary health centers across Australia. Enrollment began November 2010 and ended April 2017. Follow-up ended August 2017. Interventions: Participants were randomized to receive fluoxetine (n = 75) or placebo (n = 71). Study medication was commenced at 4 or 8 mg/d for the first week, depending on weight, and then titrated to a maximum dose of 20 or 30 mg/d over 4 weeks. Treatment duration was 16 weeks. Main Outcomes and Measures: The primary outcome was the total score on the CYBOCS-PDD (scores range from 0-20; higher scores indicate higher levels of maladaptive behaviors; minimal clinically important difference, 2 points) at 16 weeks postrandomization, analyzed with a linear regression model adjusted for stratification factors (site, age at baseline, and intellectual disability), with an additional prespecified model that included additional adjustment for baseline score, sex, communication level, and imbalanced baseline and demographic variables. Results: Among the 146 participants who were randomized (85% males; mean age, 11.2 years), 109 completed the trial; 31 in the fluoxetine group and 21 in the placebo group dropped out or did not complete treatment. The mean CYBOCS-PDD score from baseline to 16 weeks decreased in the fluoxetine group from 12.80 to 9.02 points (3.72-point decrease; 95% CI, -4.85 to -2.60) and in the placebo group from 13.13 to 10.89 points (2.53-point decrease; 95% CI, -3.86 to -1.19). The between-group mean difference at 16 weeks was -2.01 (95% CI, -3.77 to -0.25; P = .03) (adjusted for stratification factors), and in the prespecified model with further adjustment, it was -1.17 (95% CI, -3.01 to 0.67; P = .21). Conclusions and Relevance: In this preliminary study of children and adolescents with autism spectrum disorders, treatment with fluoxetine compared with placebo resulted in significantly lower scores for obsessive-compulsive behaviors at 16 weeks. Interpretation is limited by the high dropout rate, null findings of prespecified analyses that accounted for potentially confounding factors and baseline imbalances, and CIs for the treatment effect that included the minimal clinically important difference. Trial Registration: anzctr.org.au Identifier: ACTRN12608000173392.

The role of human rhinovirus (HRV) species on asthma exacerbation severity in children and adolescents.

OBJECTIVE: It is recognized that human rhinovirus (HRV) infection is an important factor in asthma exacerbations requiring hospitalization in children. However, previous studies have disagreed on the differential impact of various HRV species. We sought to assess the impact of HRV species on the severity of asthma exacerbations in children and adolescents. We also examined whether the effect of HRV species on severity was modified by age and gender. METHODS: Virus strain was determined for 113 children with HRV detectable at the time of admission for asthma exacerbation. Patient characteristics were collected on admission and exacerbation severity was scored using several validated scales. RESULTS: HRV species by itself was not associated with moderate/severe vs. mild exacerbations. Boys with HRV-C infections were more likely (OR: 3.7, 95% CI: 1.2-13.4) to have a moderate/severe exacerbation than girls with HRV-C (p = 0.04 for interaction term). Higher odds were observed in younger boys (3 years old: OR: 9.1, 95% CI: 1.8-47.1 vs 5 years old: OR: 3.3, 95% CI: 0.9-11.8 vs 7 years old: OR: 1.2, 95% CI: 0.2-6.6). In contrast, children with HRV-C infection and sensitized to pollen during the pollen season were less likely to have moderate/severe exacerbations (p = 0.01 for the interaction term). CONCLUSION: Acute asthma exacerbations are more likely to be moderate/severe in boys under 5 years of age who had HRV-C infection on admission. The opposite was found in children with sensitization to pollen during pollen season.

Acute Compensatory Responses to Interrupting Prolonged Sitting With Intermittent Activity in Preadolescent Children.

PURPOSE: The purpose of this study was to compare the effects of intermittent activity performed at varying intensities and of prolonged sitting on physical activity compensation. METHODS: A total of 33 children (14 boys and 19 girls; age 7-11 y; 24% overweight/obese; 61% nonwhite) completed 4 experimental conditions in random order: 8 hours of sitting interrupted with 20 two-minute low-, moderate-, or high-intensity activity breaks or 20 two-minute sedentary computer game breaks. Physical activity energy expenditure (PAEE) was assessed via accelerometry to establish baseline PAEE and throughout each condition day (8-h in-lab PAEE, out-of-lab PAEE, and 3-d postcondition). RESULTS: Compared with baseline PAEE, total daily PAEE was significantly higher during the high-intensity condition day (153 ± 43 kcal, P = .03), unchanged during the low-intensity (-40 ± 23 kcal, P > .05) and moderate-intensity condition days (-11 ± 18 kcal, P > .05), and decreased in response to prolonged sitting (-79 ± 22 kcal, P = .03). There were no significant differences in PAEE 3-day postcondition across conditions (P > .05). CONCLUSION: Despite the varying levels of PAEE accumulated during the 8-hour laboratory conditions, out-of-lab PAEE during each condition day and 3-day postcondition did not change from the baseline. These findings provide preliminary evidence that spontaneous physical activity in children does not change in response to intermittent activity or prolonged sitting.

Acute Effect of Intermittent Exercise and Action-Based Video Game Breaks on Math Performance in Preadolescent Children.

PURPOSE: The purpose of this study was to compare the acute effects of video game breaks and intermittent exercise breaks, performed at varying intensities, on math performance in preadolescent children. METHODS: A total of 39 children (18 males and 21 females; aged 7-11 y) completed 4 experimental conditions in random order: 8 hours of sitting interrupted with 20 two-minute low-, moderate-, or high-intensity exercise breaks or 20 two-minute sedentary computer game breaks. The intensity of exercise breaks for the low-, moderate-, and high-intensity conditions corresponded with 25%, 50%, and 75% of heart rate reserve, respectively. Math performance was assessed 3 times throughout each condition day using a 90-second math test consisting of 40 single-digit addition and subtraction questions. RESULTS: There were no significant differences in percent change in math scores (correct answers out of attempted) by condition [low: -1.3 (0.8), moderate: 0.1 (1.3), high: -1.8 (0.7), and computer: -2.5 (0.8); P > .05]. There were significant differences in percent change in math scores over the course of the condition days with lower math scores reported at end-of-day test compared with midday test [-2.4 (0.5) vs -0.4 (0.3); P = .01]. There were no significant condition × time, time × age, condition × age, or condition × time × age interactions (all Ps > .05). CONCLUSION: Action-based video game and exercise breaks elicit the same level of math performance in children; however, time of day may impact this relationship. These findings may have important implications for instructional time in elementary classrooms.

Associations between outdoor fungal spores and childhood and adolescent asthma hospitalizations.

BACKGROUND: Childhood asthma is a significant public health problem and severe exacerbations can result in diminished quality of life and hospitalization. OBJECTIVE: We sought to examine the contribution of outdoor fungi to childhood and adolescent asthma hospitalizations. METHODS: The Melbourne Air Pollen Children and Adolescent study is a case-crossover study of 644 children and adolescents (aged 2-17 years) hospitalized for asthma. The Melbourne Air Pollen Children and Adolescent study collected individual data on human rhinovirus infection and sensitization to Alternaria and Cladosporium and daily counts of ambient concentrations of fungal spores, pollen, and air pollutants. Conditional logistic regression models were used to assess associations with increases in spore counts while controlling for potential confounding and testing interactions. RESULTS: Exposure to Alternaria (adjusted odds ratio [aOR], 1.07; 95% CI, 1.03-1.11), Leptosphaeria (aOR, 1.05; 95% CI, 1.02-1.07), Coprinus (aOR, 1.04; 95% CI, 1.01-1.07), Drechslera (aOR, 1.03; 95% CI, 1.00-1.05), and total spores (aOR, 1.05; 95% CI, 1.01-1.09) was significantly associated with child asthma hospitalizations independent of human rhinovirus infection. There were significant lagged effects up to 3 days with Alternaria, Leptosphaeria, Cladosporium, Sporormiella, Coprinus, and Drechslera. Some of these associations were significantly greater in participants with Cladosporium sensitization. CONCLUSIONS: Exposures to several outdoor fungal spore taxa, including some not reported in previous research, are associated with the risk of child and adolescent asthma hospitalization, particularly in individuals sensitized to Cladosporium. We need further studies to examine cross-reactivity causing asthma exacerbations. Identifying sensitization to multiple fungal allergens in children with asthma could support the design and implementation of more effective strategies to prevent asthma exacerbations.

Association of a full-day vs part-day preschool intervention with school readiness, attendance, and parent involvement.

IMPORTANCE: Early childhood interventions have demonstrated positive effects on well-being. Whether full-day vs part-day attendance improves outcomes is unknown. OBJECTIVE: To evaluate the association between a full- vs part-day early childhood program and school readiness, attendance, and parent involvement. DESIGN, SETTING, AND PARTICIPANTS: End-of-preschool follow-up of a nonrandomized, matched-group cohort of predominantly low-income, ethnic minority children enrolled in the Child-Parent Centers (CPC) for the full day (7 hours; n = 409) or part day (3 hours on average; n = 573) in the 2012-2013 school year in 11 schools in Chicago, Illinois. INTERVENTION: The Midwest CPC Education Program provides comprehensive instruction, family-support, and health services from preschool to third grade. MAIN OUTCOMES AND MEASURES: School readiness skills at the end of preschool, attendance and chronic absences, and parental involvement. The readiness domains in the Teaching Strategies GOLD Assessment System include a total of 49 items with a score range of 105-418. The specific domains are socioemotional with 9 items (score range, 20-81), language with 6 items (score range, 15-54), literacy with 12 items (score range, 9-104), math with 7 items (score, 8-60), physical health with 5 items (score range, 14-45), and cognitive development with 10 items (score range, 18-90). RESULTS: Full-day preschool participants had higher scores than part-day peers on socioemotional development (58.6 vs 54.5; difference, 4.1; 95% CI, 0.5-7.6; P = .03), language (39.9 vs 37.3; difference, 2.6; 95% CI, 0.6-4.6; P = .01), math (40.0 vs 36.4; difference, 3.6; 95% CI, 0.5-6.7; P = .02), physical health (35.5 vs 33.6; difference, 1.9; 95% CI, 0.5-3.2; P = .006), and the total score (298.1 vs 278.2; difference, 19.9; 95% CI, 1.2-38.4; P = .04). Literacy (64.5 vs 58.6; difference, 5.9; 95% CI, -0.07 to 12.4; P = .08) and cognitive development (59.7 vs 57.7; difference, 2.0; 95% CI, -2.4 to 6.3; P = .38) were not significant. Full-day preschool graduates also had higher rates of attendance (85.9% vs 80.4%; difference, 5.5; 95% CI, 2.6-8.4; P = .001) and lower rates of chronic absences (≥10% days missed; 53.0% vs 71.6%; difference, -18.6; 95% CI, -28.5 to -8.7; P = .001; ≥20% days missed; 21.2% vs 38.8%; difference -17.6%; 95% CI, -25.6 to -9.7; P < .001) but no differences in parental involvement. CONCLUSIONS AND RELEVANCE: In an expansion of the CPCs in Chicago, a full-day preschool intervention was associated with increased school readiness skills in 4 of 6 domains, attendance, and reduced chronic absences compared with a part-day program. These findings should be replicated in other programs and contexts.

Cellular mechanotransduction of human osteoblasts in microgravity.

Astronauts experience significant and rapid bone loss as a result of an extended stay in space, making the International Space Station (ISS) the perfect laboratory for studying osteoporosis due to the accelerated nature of bone loss on the ISS. This prompts the question, how does the lack of load due to zero-gravity propagate to bone-forming cells, human fetal osteoblasts (hFOBs), altering their maturation to mineralization? Here, we aim to study the mechanotransduction mechanisms by which bone loss occurs in microgravity. Two automated experiments, 4 microfluidic chips capable of measuring single-cell mechanics of hFOBs via aspiration and cell spheroids incubated in pressure-controlled chambers, were each integrated into a CubeLab deployed to the ISS National Laboratory. For the first experiment, we report protrusion measurements of aspirated cells after exposure to microgravity at the ISS and compare these results to ground control conducted inside the CubeLab. Our analysis revealed slightly elongated protrusions for space samples compared to ground samples indicating softening of hFOB cells in microgravity. In the second experiment, we encapsulated osteoblast spheroids in collagen gel and incubated the samples in pressure-controlled chambers. We found that microgravity significantly reduced filamentous actin levels in the hFOB spheroids. When subjected to pressure, the spheroids exhibited increased pSMAD1/5/9 expression, regardless of the microgravity condition. Moreover, microgravity reduced YAP expression, while pressure increased YAP levels, thus restoring YAP expression for spheroids in microgravity. Our study provides insights into the influence of microgravity on the mechanical properties of bone cells and the impact of compressive pressure on cell behavior and signaling in space.

Cellular mechanotransduction of human osteoblasts in microgravity.

Astronauts experience significant and rapid bone loss as a result of an extended stay in space, making the International Space Station (ISS) the perfect laboratory for studying osteoporosis due to the accelerated nature of bone loss on the ISS. This prompts the question, how does the lack of load due to zero-gravity propagate to bone-forming cells, human fetal osteoblasts (hFOBs), altering their maturation to mineralization? Here, we aim to study the mechanotransduction mechanisms by which bone loss occurs in microgravity. Two automated experiments, microfluidic chips capable of measuring single-cell mechanics via aspiration and cell spheroids incubated in pressure-controlled chambers, were each integrated into a CubeLab deployed to the ISS National Laboratory. For the first experiment, we report protrusion measurements of aspirated cells after exposure to microgravity at the ISS and compare these results to ground control conducted inside the CubeLab. We found slightly elongated protrusions for space samples compared to ground samples indicating softening of hFOB cells in microgravity. In the second experiment, we encapsulated osteoblast spheroids in collagen gel and incubated the samples in pressure-controlled chambers. We found that microgravity significantly reduced filamentous actin levels in the hFOB spheroids. When subjected to pressure, the spheroids exhibited increased pSMAD1/5/9 expression, regardless of the microgravity condition. Moreover, microgravity reduced YAP expression, while pressure increased YAP levels, thus restoring YAP expression for spheroids in microgravity. Our study provides insights into the influence of microgravity on the mechanical properties of bone cells and the impact of compressive pressure on cell signaling in space.

Iodine and Carbonate Species Monitoring in Molten NaOH-KOH Eutectic Scrubber via Dual-Phase In Situ Raman Spectroscopy.

Molten hydroxide scrubbing of off-gas vapors is a potential process to improve safety during the operation of generation IV molten salt nuclear reactors (MSRs). MSRs produce off-gases that can be vented by the reactor core and treated via off-gas scrubbers. Molten hydroxide scrubbers focus on capturing volatile iodine radionuclides, and they can also be used to capture aerosols and particulates and to neutralize acidic species. The performance of these scrubbers depends on the chemical interactions of the scrubbing medium with the off-gas species. Knowledge of the concentration and speciation of scrubbed or target species, as well as process and environmental interferents, can enable advanced operation of MSR off-gas treatment systems. Optical online monitoring is an excellent technology to provide this information in real time, while limiting the need for operators to interact with radioactive samples through hands-on interrogation. Raman spectroscopy can provide crucial chemical information on the state of the molten eutectic during treatment in the molten phase, as well as the gas phase. In this work, Raman spectroscopy is used to detect iodine species, specifically iodate, in the molten phase of a NaOH-KOH eutectic and to construct a calibration curve of the Raman signal of those species. Additionally, a carbonate interferent is followed from the gas phase to the liquid phase as a basis for reaching a Raman-aided mass balance of the molten hydroxide eutectic scrubber system.

Current state of prognostication, therapy and prospective innovations for Barrett's-related esophageal adenocarcinoma: a literature review.

OBJECTIVE: Barrett's esophagus (BE) is the only known precursor to esophageal adenocarcinoma (EAC), which has one of the lowest 5-year survival rates in oncology. The reasons for poor survival are twofold: the large majority of diagnoses are in advanced stages (~80%) and limited treatment options, with a deficit of biology-guided therapies. As a rapidly growing public health concern with poor prognosis, research into the molecular progression for BE and novel therapeutics for EAC currently has high clinical utility. Review of the literature reveals that innovative analysis of metaplastic progression from BE to EAC at a molecular level can shed light on the underlying transformative probabilities of BE into malignant pathologies and may impact current of future therapeutic modalities for management of these diseases. BACKGROUND: EAC is the fastest increasing cancer in the United States with a 600% increase over the past 25 years. This cancer arises from dysplastic tissue of BE, a complication of gastroesophageal reflux disease (GERD). Chronic acid and bile reflux in the distal esophagus initiates a metaplastic conversion of normal squamous epithelium to premalignant intestinalized columnar epithelium. Patients with BE have a 125-fold higher risk of cancer compared to the general population. METHODS: We critically reviewed the current status of BE monitoring, and subsequent therapeutic strategies being used in patients who have progressed to cancer. Also, new diagnostic tools and therapeutic candidates for BE-related EAC are discussed. Highly-targeted searches of databases containing recent original peer-reviewed papers were utilized for this review. CONCLUSIONS: Novel and well-described biomarkers analyzed in the patient's diseased tissue will provide for more powerful diagnostics, but also possess the potential to develop strategies for personalized management and identify targets for intervention to either cease disease progression or treat BE and/or EAC. Since millions of Americans develop BE without progressing to cancer, there is a critical need to identify the small percentage of Barrett's patients who possess hallmarks of disease progression or carcinogenesis with novel screening techniques. Incorporation of such tools into standard screening protocols for BE surveillance and/or therapy would be critical to detect malignant transformations before clinically obvious cancer ever develops.

1,4,5,8-Naphthalene tetracarboxylate dianhydride/g-C3N4 van der Waals heterojunctions exhibit enhanced photochemical H2O2 production and antimicrobial activity.

Organic semiconductors, including graphitic carbon nitride (g-C3N4, CN), represent an important class of materials for the development of novel antimicrobial or biomedical technologies. Of principal interest is the ability of these materials to catalyze the reduction of elemental oxygen to generate reactive oxygen species (ROS), including hydrogen peroxide (H2O2). Here, we describe the fabrication of photoactive van der Waals heterojunctions incorporating 1,4,5,8-naphthalene tetracarboxylic dianhydride (NTCDA) and CN. The composite heterojunction systems were characterized by a combination of physical (TEM, SEM, pXRD), spectroscopic (FT-IR, XPS, DRUV, photoluminescence, TCSPC) and kinetic experiments. Electronic interactions between the two components of the heterojunction increase the rate of photochemical production of H2O2 from elemental oxygen by 410%, relative to samples of pure CN. Mechanistic analysis reveals that interaction of NTCDA with the surface of CN modifies the mechanism of H2O2 formation in the heterojunction photocatalysts. The photochemical production of H2O2 by irradiation of the most active heterojunction composition is sufficient to reduce the viability of E. coli O157:H7, S. aureus and Ps. aeruginosa PAO1 by 99%. Importantly, H2O2 production by the NTCDA/CN heterojunctions suppresses Ps. aeruginosa biofilm formation, even at light exposure doses that had a lesser impact on overall planktonic cell growth.

Radiation and Androgen Deprivation Therapy With or Without Docetaxel in the Management of Nonmetastatic Unfavorable-Risk Prostate Cancer: A Prospective Randomized Trial.

PURPOSE: Although docetaxel is not recommended when managing men with unfavorable-risk prostate cancer (PC) given negative or inconclusive results from previous randomized trials, unstudied benefits may exist. METHODS: Between September 21, 2005, and January 13, 2015, we randomly assigned 350 men 1:1 with T1c-4N0M0 unfavorable-risk PC to receive radiation therapy (RT) and androgen deprivation therapy (ADT) plus docetaxel (60 mg/m2 once every 3 weeks for three cycles before RT and 20 mg/m2 once weekly during RT) versus ADT + RT. We evaluated the treatment effect of adding docetaxel to ADT + RT on the primary end point of overall survival (OS) and the incidence of RT-induced cancers and explored whether the impact of the treatment effect on OS differed within prostate-specific antigen (PSA) subgroups (< 4, > 20 v 4-20 ng/mL) using the interaction test for heterogeneity adjusted for age and PC prognostic factors. RESULTS: After a median follow-up of 10.2 years, 89 men died (25.43%); of these, 42 from PC (47.19%). Although OS was not significantly increased in the docetaxel arm (the restricted mean survival time over 10 years was 9.11 v 8.82 years; P = .22), significantly fewer RT-induced cancers were observed (10-year estimates: 0.61% v 4.90%; age-adjusted hazard ratio of 0.13; 95% CI, 0.02 to 0.97; P = .046). The treatment effect of adding docetaxel to ADT + RT on OS significantly differed in men with a PSA < 4 ng/mL versus 4-20 ng/mL (adjusted hazard ratio: 0.27 and 1.51, respectively) because of less PC-specific mortality on the docetaxel arm (0.00% v 28.57%) among men with PSA < 4 ng/mL. CONCLUSION: Adding docetaxel to ADT + RT did not prolong OS in men with unfavorable-risk PC, but decreased RT-induced cancer incidence, and may prolong OS in the subgroup of men with a PSA < 4 ng/mL by reducing PC-specific mortality.

Effects of apodization smoothing and denoising on spectral fitting.

PURPOSE: Visual review of individual spectra in magnetic resonance spectroscopic imaging (MRSI) data benefits from the application of spectral smoothing; however, if this processing step is applied prior to spectral analysis this can impact the accuracy of the quantitation. This study aims to analyze the effect of spectral denoising and apodization smoothing on the quantitation of whole-brain MRSI data obtained at short TE. METHODS: Short-TE MRSI data obtained at 3 T were analyzed with no spectral smoothing, following (i) Gaussian apodization with values of 1, 2, 4, 6, and 8 Hz, and (ii) denoising using principal component analysis (dnPCA) with 3 different values for the number of retained principal components. The mean lobar white matter estimates for four metabolites, signal-to-noise ratio (SNR), spectral linewidth, and confidence intervals were compared to data reconstructed using no smoothing. Additionally, a voxel-wise comparison for N-acetylaspartate quantitation with different smoothing schemes was performed. RESULTS: Significant pairwise differences were seen for all Gaussian smoothing methods as compared to no smoothing (p<0.001) in linewidth and metabolite estimates, whereas dnPCA methods showing no statistically significant differences in these measures. Confidence intervals decreased, and SNR increased with increasing levels of apodization smoothing or dnPCA denoising. CONCLUSION: Mild Gaussian apodization (≤2 Hz at 3 T) can be applied with minimal (1%) errors in quantitation; however, smoothing values greater than that can significantly affect metabolite quantification. In contrast, mild to moderate dnPCA based denoising provides quantitative results that are consistent with the analysis of unsmoothed data and this method is recommended for spectral denoising.

Acute Effects of Intermittent Physical Activity on Perceptions of Exercise-Related Fatigue in Children.

PURPOSE: To investigate the acute effects of intermittent activity performed at varying intensities on the perceptions of exercise-related fatigue in children. METHODS: A total of 30 children completed 4 experimental conditions in random order, which consisted of 8 hours of sitting interrupted with 20 two-minute low-, moderate-, or high-intensity activity breaks or 20 two-minute sedentary breaks. The perceptions of exercise-related fatigue were determined via the Subjective Exercise Experience Scale at the beginning (0 breaks), middle (after 10 breaks), and end (after 20 breaks) of each condition. RESULTS: The average heart rate was significantly higher with increasing exercise intensity (sedentary: 89.6 ± 1.2 beats/min, low: 114.6 ± 1.8 beats/min, moderate: 147.2 ± 1.8 beats/min, and high: 172.3 ± 1.8 beats/min, P < .0001). There was no significant main effect of condition (sedentary: -0.5 ± 0.6, low: -1.0 ± 0.7, moderate: -0.2 ± 0.5, and high: -0.6 ± 1.2; P = .86) and time (10-0 breaks: -0.7 ± 0.5 and 20-0 breaks: -0.5 ± 0.5; P = .45), nor time by condition interaction (P = .99) on change in exercise-related fatigue. CONCLUSIONS: Incorporating intermittent activity into physical activity programs may help to reduce barriers to regular exercise by minimizing perceptions of exercise-related fatigue in children.

The effects of power and stretch yoga on affect and salivary cortisol in women.

Yoga practice is known to improve well-being and decrease stress. However, acute yoga is understudied. This study investigated the effects of two different types of yoga on affect and salivary cortisol levels in college women. Thirty-three women aged 18-30 years each completed 1-hour sessions of power yoga and stretch yoga. Measures of affect and salivary cortisol were assessed before, during, and after each session. Participants perceived power yoga to be more pleasurable and energizing. Salivary cortisol significantly decreased after both yoga sessions. Thus, even one session of yoga may be effective in improving affect and decreasing stress in college women.