Padres Preparados, Jóvenes Saludables: intervention impact of a randomized controlled trial on Latino father and adolescent energy balance-related behaviors.

BACKGROUND: Studies have shown associations among food and activity behaviors and body weight of Latino fathers and adolescents. However, few Latino father-focused interventions have been designed to improve energy balance-related behaviors (EBRBs) and weight status among early adolescents. Thus, this efficacy study aims to evaluate the Padres Preparados, Jóvenes Saludables (Padres) youth obesity prevention program for positive changes in EBRBs (fruit, vegetable, sugar-sweetened beverage (SSB), sweet/salty snack, and fast-food consumption, physical activity, and screen time) and weight status among low-income Latino fathers and adolescents (10-14 years). METHODS: A two-arm (treatment versus delayed-treatment control group) randomized controlled trial was conducted to evaluate the efficacy of 8 weekly experiential learning sessions (2.5 hours each) based on social cognitive theory. The sessions included food preparation, parenting skills, nutrition, and physical activity. The program was delivered to father-adolescent dyads (mothers were encouraged to attend) in trusted community-based settings in a Midwest metropolitan area between 2017 and 2019. In March 2020, in-person implementation was discontinued due to COVID-19 pandemic restrictions, which limited the sample size. Father/adolescent dyads were randomized to treatment or control group within each site. Surveys and measurements were completed by fathers and adolescents to assess changes in food and activity behaviors from baseline to post-intervention. Adolescents also completed 24-hour dietary recall interviews at baseline and post-intervention. Intervention effects were assessed using linear regression mixed models adjusted for covariates and accounting for clustering of participants within sites. RESULTS: Data from 147 father/adolescent dyads who completed at least the baseline data collection were used. No significant differences were observed for baseline to post-intervention changes in adolescents' and fathers' EBRBs or weight status between treatment and control groups. Fathers' SSB and fast food intakes were not statistically significant (p = 0.067 and p = 0.090, respectively). CONCLUSIONS: The Padres program resulted in no significant improvements in adolescent and father EBRBs and weight status. Additional Latino father-focused interventions are needed to examine intervention effects on EBRBs among Latino adolescents. TRIAL REGISTRATION: The Padres Preparados, Jóvenes Saludables study is registered with the U.S. National Library of Medicine, ClinicalTrials.gov Identifier: NCT03469752 (19/03/2018).

The accuracy of external calibration markers in digital templating using the double marker and single marker method: a comparative study.

BACKGROUND: Digital templating is an essential step in the preoperative planning of total hip arthroplasty (THA). Previous studies have suggested that templating with the double marker method may be more accurate than a single marker method in the general population and in obese patients. The purpose of this study was to compare the accuracy in the preoperative component selection between the King Mark calibration device and the conventional metal ball method. Additionally, we examined whether King Mark offered any advantage over the standard metal ball in the preoperative selection of component sizes for obese patients. METHODS: We retrospectively reviewed patients who underwent preoperative digital templating for THA in our center from January 2014 to January 2016 with King Mark device and marker ball. We compared the preoperative template component size and offset with the intraoperative definite implant size. The accuracy was defined as the difference between preoperative and intraoperative component sizes. The overall accepted calibration was defined as an exact match ± one size. Patients were stratified into two cohorts according to the calibration method: standard marker ball technique and King Mark technique. RESULTS: 126 THA underwent digital calibration. 79 patients underwent a preoperative templating using the King Mark calibration device. 47 patients were templated using a conventional marker ball. The overall adequate preoperative planning of the acetabular cup (exact or ± 1 size match) in the King Mark group did not differ from the single marker method (74.7% and 74.5%, respectively, p = 0.979). No significant difference was noted in the overall accepted calibration of the femoral stem (exact or ± 1 size match) between the marker ball group and the King Mark group (58.2% and 70.2%, respectively, p = 0.179). The King Mark group showed a better preoperative planning for the stem's offset compared to the marker ball group (77.2% % and 61.7%, respectively, p = 0.062). For the obese patient cohort, no significant difference was noted between the King Mark group and the marker ball group in the exact prediction of the acetabular cup and the femoral stem, (p = 0.31 and p = 0.15, respectively). CONCLUSIONS: Our study found no difference between the King Mark method and the conventional metal ball method in the ability to accurately predict component sizes. In the subgroup of obese patients, the King Mark technique offered no advantage for accurately predicting component sizes.

Understanding the Early Biological Effects of Isoprene-Derived Particulate Matter Enhanced by Anthropogenic Pollutants.

INTRODUCTION: Airborne fine particulate matter (PM2.5; particulate matter ≤ 2.5 µm in aerodynamic diameter) plays a key role in air quality, climate, and public health. Globally, the largest mass fraction of PM2.5 is organic, dominated by secondary organic aerosol (SOA) formed from atmospheric oxidation of volatile organic compounds (VOCs). Isoprene from vegetation is the most abundant nonmethane VOC emitted into Earth's atmosphere. Isoprene has been recently recognized as one of the major sources of global SOA production that is enhanced by the presence of anthropogenic pollutants, such as acidic sulfate derived from sulfur dioxide (SO2), through multiphase chemistry of its oxidation products. Considering the abundance of isoprene-derived SOA in the atmosphere, understanding mechanisms of adverse health effects through inhalation exposure is critical to mitigating its potential impact on public health. Although previous studies have examined the toxicological effects of certain isoprene-derived gas-phase oxidation products, to date, no systematic studies have examined the potential toxicological effects of isoprene-derived SOA, its constituents, or its SOA precursors on human lung cells. SPECIFIC AIMS: The overall objective of this study was to investigate the early biological effects of isoprene-derived SOA and its subtypes on BEAS-2B cells (a human bronchial epithelial cell line), with a particular focus on the alteration of oxidative stress- and inflammation-related genes. To achieve this objective, there were two specific aims.1. Examine toxicity and early biological effects of SOA derived from the photochemical oxidation of isoprene, considering both urban and downwind-urban types of chemistry.2. Examine toxicity and early biological effects of SOA derived directly from downstream oxidation products of isoprene (i.e., epoxides and hydroperoxides). METHODS: Isoprene-derived SOA was first generated by photooxidation of isoprene under natural sunlight in the presence of nitric oxide (NO) and acidified sulfate aerosols. Experiments were conducted in a 120-m3 outdoor Teflon-film chamber located on the roof of the Gillings School of Global Public Health, University of North Carolina at Chapel Hill (UNC-Chapel Hill). BEAS-2B cells were exposed to chamber- generated isoprene-derived SOA using the Electrostatic Aerosol in Vitro Exposure System (EAVES). This approach allowed us to generate atmospherically relevant compositions of isoprene-derived SOA and to examine its toxicity through in vitro exposures at an air-liquid interface, providing a more biologically relevant exposure model. Isoprene-derived SOA samples were also collected, concurrently with EAVES sampling, onto Teflon membrane filters for in vitro resuspension exposures and for analysis of aerosol chemical composition by gas chromatography/electron ionization-quadrupole mass spectrometry (GC/EI-MS) with prior trimethylsilylation and ultra-performance liquid-chromatography coupled to high-resolution quadrupole time-of-flight mass spectrometry equipped with electrospray ionization (UPLC/ESI-HR-QTOFMS). Isoprene-derived SOA samples were also analyzed by the dithiothreitol (DTT) assay in order to characterize their reactive oxygen species (ROS)-generation potential.Organic synthesis of known isoprene-derived SOA precursors, which included isoprene epoxydiols (IEPOX), methacrylic acid epoxide (MAE), and isoprene-derived hydroxyhydroperoxides (ISOPOOH), was conducted in order to isolate major isoprene-derived SOA formation pathways from each other and to determine which of these pathways (or SOA types) is potentially more toxic. Since IEPOX and MAE produce SOA through multiphase chemistry onto acidic sulfate aerosol, dark reactive uptake experiments of IEPOX and MAE in the presence of acidic sulfate aerosol were performed in a 10-m3 flexible Teflon indoor chamber at UNC-Chapel Hill. Since the generation of SOA from ISOPOOH (through a non-IEPOX route) requires a hydroxyl radical (•OH)-initiated oxidation, ozonolysis of tetramethylethylene (TME) was used to form the needed •OH radicals in the indoor chamber. The resultant low-volatility multifunctional hydroperoxides condensed onto nonacidified sulfate aerosol, yielding the ISOPOOH-derived SOA needed for exposures. Similar to the outdoor chamber SOAs, IEPOX, MAE- and ISOPOOH-derived SOAs were collected onto Teflon membrane filters and were subsequently chemically characterized by GC/EI-MS and UPLC/ESI-HR-QTOFMS as well as for ROS-generation potential using the DTT assay. These filters were also used for resuspension in vitro exposures.By conducting gene expression profiling, we provided mechanistic insights into the potential health effects of isoprene-derived SOA. First, gene expression profiling of 84 oxidative stress- and 249 inflammation-associated human genes was performed for cells exposed to isoprene-derived SOA generated in our outdoor chamber experiments in EAVES or by resuspension. Two pathway-focused panels were utilized for this purpose: (1) nCounter GX Human Inflammation Kit comprised of 249 human genes (NanoString), and (2) Human Oxidative Stress Plus RT2 Profiler PCR Array (Qiagen) comprised of 84 oxidative stress-associated genes. We compared the gene expression levels in cells exposed to SOA generated in an outdoor chamber from photochemical oxidation of isoprene in the presence of NO and acidified sulfate seed aerosol to cells exposed to a dark control mixture of isoprene, NO, and acidified sulfate seed aerosol to isolate the effects of the isoprene-derived SOA on the cells using the EAVES and resuspension exposure methods. Pathway-based analysis was performed for significantly altered genes using the ConsensusPathDB database, which is a database system for the integration of human gene functional interactions to provide biological pathway information for a gene set of interest. Pathway annotation was performed to provide biological pathway information for each gene set. The gene-gene interaction networks were constructed and visualized using the GeneMANIA Cytoscape app (version 3.4.1) to predict the putative function of altered genes. Lastly, isoprene-derived SOA collected onto filters was used in resuspension exposures to measure select inflammatory biomarkers, including interleukin 8 (IL-8) and prostaglandin-endoperoxide synthase 2 (PTGS2) genes, in BEAS-2B cells to ensure that effects observed from EAVES exposures were attributable to particle-phase organic products. Since EAVES and resuspension exposures compared well, gene expression profiling for IEPOX-, MAE- and ISOPOOH-derived SOA were conducted using only resuspension exposures. RESULTS AND CONCLUSIONS: Chemical characterization coupled with biological analyses show that atmospherically relevant compositions of isoprene-derived SOA alter the levels of 41 oxidative stress-related genes. Of the different composition types of isoprene-derived SOA, MAE- and ISOPOOH-derived SOA altered the greatest number of genes, suggesting that carbonyl and hydroperoxide functional groups are oxidative stress promoters. Taken together, the different composition types accounted for 34 of the genes altered by the total isoprene-derived SOA mixture, while 7 remained unique to the total mixture exposures, indicating that there is either a synergistic effect of the different isoprene-derived SOA components or an unaccounted component in the mixture.The high-oxides of nitrogen (NOx) regime, which yielded MAE- and methacrolein (MACR)-derived SOA, had a higher ROS-generation potential (as measured by the DTT assay) than the low- NOx regime, which included IEPOX- and isoprene-derived SOA. However, ISOPOOH-derived SOA, which also formed in the low- NOx regime, had the highest ROS-generation potential, similar to 1,4-naphthoquinone (1,4-NQ). This suggests that aerosol-phase organic peroxides contribute significantly to particulate matter (PM) oxidative potential. MAE- and MACR- derived SOA showed equal or greater ROS-generation potential than was reported in prior UNC-Chapel Hill studies on diesel exhaust PM, highlighting the importance of a comprehensive investigation of the toxicity of isoprene-derived SOA. Notably, ISOPOOH-derived SOA was one order of magnitude higher in ROS-generation potential than diesel exhaust particles previously examined at UNC-Chapel Hill. As an acellular assay, the DTT assay may not be predictive of oxidative stress; therefore, we also focused on the gene expression results from the cellular exposures.We have demonstrated that the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and the redox-sensitive activation protein-1 (AP-1) transcription factor networks have been significantly altered upon exposure to isoprene-derived SOA. The identification of Nrf2 pathway in cells exposed to isoprene-derived SOA is in accordance with our findings using the DTT assay, which measures the thiol reactivity of PM samples as a surrogate for their ROS-generation potential. Specifically, our results point to the cysteine-thiol modifications within cells that lead to activation of Nrf2-related gene expression.However, based on our gene expression results showing no clear relationship between DTT activity and the number of altered oxidative stress-related genes, the DTT activity of isoprene-derived SOA may not be directly indicative of toxicity relative to other SOA types. While activation of Nrf2-associated genes has been identified with responses to oxidative stress and linked to traffic related air pollution exposure in both toxicological and epidemiological studies, their implicit involvement in this study suggests that activation of Nrf2-related gene expression may occur with exposures to all sorts of PM types.By controlling the exposure time, method, and dose we demonstrated that among the SOA derived from previously identified individual precursors of isoprene-derived SOA, ISOPOOH-derived SOA alters moreoxidative stress related genes than does IEPOX-derived SOA, but fewer than MAE-derived SOA. This suggests that the composition of MAE-derived SOA may be the greatest contributor to alterations of oxidative stress-related gene expression observed due to isoprene-derived SOA exposure. Further study on induced levels of protein expression and specific toxicological endpoints is necessary to determine if the observed gene expression changes lead to adverse health effects. In addition, such studies have implications for pollution-control strategies because NOx and SO2 are controllable pollutants that can alter the composition of SOA, and in turn alter its effects on gene expression. The mass fraction of different components of atmospheric isoprene derived SOA should be considered, but altering the fraction of high- NOx isoprene-derived SOA (e.g., MAE derived SOA) may yield greater changes in gene expression than altering the fraction of low- NOx isoprene derived SOA types (ISOPOOH- or IEPOX-derived SOA). Finally, this study confirms that total isoprene-derived SOA alters the expression of a greater number of genes than does SOA derived from the tested precursors. This warrants further work to determine the underlying explanation for this observation, which may be uncharacterized components of isoprene-derived SOA or the potential for synergism between the studied components.

Molecular Composition and Volatility of Organic Aerosol in the Southeastern U.S.: Implications for IEPOX Derived SOA.

We present measurements as part of the Southern Oxidant and Aerosol Study (SOAS) during which atmospheric aerosol particles were comprehensively characterized. We present results utilizing a Filter Inlet for Gases and AEROsol coupled to a chemical ionization mass spectrometer (CIMS). We focus on the volatility and composition of isoprene derived organic aerosol tracers and of the bulk organic aerosol. By utilizing the online volatility and molecular composition information provided by the FIGAERO-CIMS, we show that the vast majority of commonly reported molecular tracers of isoprene epoxydiol (IEPOX) derived secondary organic aerosol (SOA) is derived from thermal decomposition of accretion products or other low volatility organics having effective saturation vapor concentrations <10(-3) µg m(-3). In addition, while accounting for up to 30% of total submicrometer organic aerosol mass, the IEPOX-derived SOA has a higher volatility than the remaining bulk. That IEPOX-SOA, and more generally bulk organic aerosol in the Southeastern U.S. is comprised of effectively nonvolatile material has important implications for modeling SOA derived from isoprene, and for mechanistic interpretations of molecular tracer measurements. Our results show that partitioning theory performs well for 2-methyltetrols, once accretion product decomposition is taken into account. No significant partitioning delays due to aerosol phase or viscosity are observed, and no partitioning to particle-phase water or other unexplained mechanisms are needed to explain our results.

Usability testing of the Internet program: "Teens Taking Charge: Managing My Transplant Online".

Adolescents with SOT demonstrate high rates of medication non-adherence and higher rates of graft loss compared to all other age groups. Self-management interventions encompass information-based material designed to achieve disease-related learning and changes in the participant's knowledge and skill acquisition, while providing social support. These interventions have had some success in chronic disease populations by reducing symptoms and promoting self-efficacy and empowerment. Using findings from a needs assessment, an Internet-based self-management program, Teens Taking Charge: Managing My Transplant Online, for youth with SOT was developed. This program contains information on transplant, self-management and transition skills, and opportunities for peer support. The purpose of this study was to determine the usability and acceptability of the initial three modules (Medication and Vaccines; Diet after Transplant; and Living with a Transplant Organ) of the online program from the perspectives of youth with SOT. Participants were recruited from SOT clinics at a large pediatric tertiary care center in Canada. Three iterative cycles (seven patients per iteration) of usability testing took place to refine the Web site prototype. Study procedures involved participants finding items from a standardized list of features and talking aloud about issues they encountered, followed by a semi-structured interview to generate feedback about what they liked and disliked about the program. All 21 patients (mean age = 14.9 yr) found the Web site content to be trustworthy, they liked the picture content, and they found the videos of peer experiences to be particularly helpful. Participants had some difficulties finding information within submodules and suggested a more simplistic design with easier navigation. This web-based intervention is appealing to teenagers and may foster improved self-management with their SOT. Nine additional teen and two parent modules are being developed, and the completed Web site will undergo usability testing. In the future, a randomized control trial will determine the feasibility and effectiveness of this online self-management program on adherence, self-efficacy, and transition skills.

Fecal Bacteria Contamination of Floodwaters and a Coastal Waterway From Tidally-Driven Stormwater Network Inundation.

Inundation of coastal stormwater networks by tides is widespread due to sea-level rise (SLR). The water quality risks posed by tidal water rising up through stormwater infrastructure (pipes and catch basins), out onto roadways, and back out to receiving water bodies is poorly understood but may be substantial given that stormwater networks are a known source of fecal contamination. In this study, we (a) documented temporal variation in concentrations of Enterococcus spp. (ENT), the fecal indicator bacteria standard for marine waters, in a coastal waterway over a 2-month period and more intensively during two perigean spring tide periods, (b) measured ENT concentrations in roadway floodwaters during tidal floods, and (c) explained variation in ENT concentrations as a function of tidal inundation, antecedent rainfall, and stormwater infrastructure using a pipe network inundation model and robust linear mixed effect models. We find that ENT concentrations in the receiving waterway vary as a function of tidal stage and antecedent rainfall, but also site-specific characteristics of the stormwater network that drains to the waterway. Tidal variables significantly explain measured ENT variance in the waterway, however, runoff drove higher ENT concentrations in the receiving waterway. Samples of floodwaters on roadways during both perigean spring tide events were limited, but all samples exceeded the threshold for safe public use of recreational waters. These results indicate that inundation of stormwater networks by tides could pose public health hazards in receiving water bodies and on roadways, which will likely be exacerbated in the future due to continued SLR.

Dose Adjustment for Normal Eating (DAFNE) in routine clinical practice: who benefits?

AIMS: To explore the effectiveness of Dose Adjustment for Normal Eating in routine clinical practice in the UK. METHODS: Participants were 124 adults with Type 1 diabetes who had completed a Dose Adjustment for Normal Eating course. Data were collected before the course and again 1 year later on a variety of biological, psychological and social measures. RESULTS: There were a range of significant benefits consistent with Dose Adjustment for Normal Eating aims, including: better control among those with baseline HbA(1c) ≥ 81 mmol/mol (9.6%) (z = -2.8, P = 0.004); reduced number of participants reporting severe hypoglycaemia (χ² = 4.27, P = 0.039); total eradication of diabetic ketoacidosis (χ² = 4.17, P = 0.041) and lower diabetes-related distress (z = -4.5, P < 0.001). The most deprived of the clinic population were significantly under-represented (χ² = 17.8, P = 0.001) and the levels of clinical depression were unusually low. CONCLUSIONS: These results indicate that Dose Adjustment for Normal Eating delivered in routine clinical practice is associated with a range of benefits and that certain clinical and psychosocial characteristics are associated with better outcomes.

Decreased regional cerebral blood flow in medial prefrontal cortex during trauma-unrelated stressful imagery in Vietnam veterans with post-traumatic stress disorder.

BACKGROUND: Neuroimaging research has demonstrated medial prefrontal cortex (mPFC) hyporesponsivity and amygdala hyperresponsivity to trauma-related or emotional stimuli in post-traumatic stress disorder (PTSD). Relatively few studies have examined brain responses to the recollection of stressful, but trauma-unrelated, personal events in PTSD. In the current study, we sought to determine whether regional cerebral blood flow (rCBF) abnormalities in mPFC and amygdala in PTSD could be observed during the recollection of trauma-unrelated stressful personal events. METHOD: Participants were 35 right-handed male combat veterans (MCVs) and female nurse veterans (FNVs) who served in Vietnam: 17 (seven male, 10 female) with current military-related PTSD and 18 (nine male, nine female) with no current or lifetime PTSD. We used positron emission tomography (PET) and script-driven imagery to study rCBF during the recollection of trauma-unrelated stressful versus neutral and traumatic events. RESULTS: Voxelwise tests revealed significant between-group differences for the trauma-unrelated stressful versus neutral comparison in mPFC, specifically in the anterior cingulate cortex (ACC). Functional region of interest (ROI) analyses demonstrated that this interaction in mPFC represented greater rCBF decreases in the PTSD group during trauma-unrelated stressful imagery relative to neutral imagery compared to the non-PTSD group. No differential amygdala activation was observed between groups or in either group separately. CONCLUSIONS: Veterans with PTSD, compared to those without PTSD, exhibited decreased rCBF in mPFC during mental imagery of trauma-unrelated stressful personal experiences. Functional neuroanatomical models of PTSD must account for diminished mPFC responses that extend to emotional stimuli, including stressful personal experiences that are not directly related to PTSD.

Analyzing long-term water quality of lakes in Rhode Island and the northeastern United States with an anomaly approach.

Addressing anthropogenic impacts on aquatic ecosystems is a focus of lake management. Controlling phosphorus and nitrogen can mitigate these impacts, but determining management effectiveness requires long-term datasets. Recent analysis of the LAke multi-scaled GeOSpatial and temporal database for the Northeast (LAGOS-NE) United States found stable water quality in the northeastern and midwestern United States; however, sub-regional trends may be obscured. We used the University of Rhode Island's Watershed Watch Volunteer Monitoring Program (URIWW) dataset to determine if there were sub-regional (i.e., 3000 km2) water quality trends. URIWW has collected water quality data on Rhode Island lakes and reservoirs for over 25 yr. The LAGOS-NE and URIWW datasets allowed for comparison of water quality trends at regional and sub-regional scales, respectively. We assessed regional (LAGOS-NE) and sub-regional (URIWW) trends with yearly median anomalies calculated on a per-station basis. Sub-regionally, temperature and chlorophyll a increased from 1993 to 2016. Total nitrogen, total phosphorus, and the nitrogen:phosphorus ratio (N:P) were stable. At the regional scale, the LAGOS-NE dataset showed similar trends to prior studies of the LAGOS-NE with chlorophyll a, total nitrogen, and N:P all stable over time. Total phosphorus did show a very slight increase. In short, algal biomass, as measured by chlorophyll a in Rhode Island lakes and reservoirs increased, despite stability in total nitrogen, total phosphorus, and the nitrogen to phosphorus ratio. Additionally, we demonstrated both the value of long-term monitoring programs, like URIWW, for identifying trends in environmental condition, and the utility of site-specific anomalies for analyzing for long-term water quality trends.

Severe hypoglycaemia during pregnancy in women with Type 1 diabetes is common and planning pregnancy does not decrease the risk.

AIMS: The aim of this study was to identify risk factors for severe hypoglycaemia (SH) in pregnancy in Type 1 diabetes, including associations with pregnancy planning and glycaemic control. METHODS: Clinical data including details of the pregnancy and its outcome, glycaemic control, frequency of SH and evidence of pregnancy planning were collected prospectively as part of a national audit of 160 pregnancies in women with Type 1 diabetes. RESULTS: An episode of SH was experienced by 29.4% of women at some point during the pregnancy, with the percentage of women experiencing SH decreasing from 21.9% in the first trimester to 18.1% in trimester 2 and 10.9% in trimester 3. Longer duration of diabetes was associated with increased frequency of SH during pregnancy (r = 0.191, P = 0.012). A greater fall in glycated haemoglobin (HbA(1c)) between pre-pregnancy and the first trimester was not associated with increased risk of SH in trimester 1. Planned pregnancies had better glycaemic control but higher risk of SH in trimester 1 (P = 0.047). Women with pre-pregnancy retinopathy and current smokers had an increased risk of SH in trimester 3 (P = 0.029, P = 0.033). CONCLUSIONS: SH is common during pregnancy and particularly in the first trimester. Planning pregnancy does not decrease the risk of SH. Improvements in glycaemic control at the start of pregnancy do not appear to increase the risk of SH. Education of women and their partners about the risks of SH and its management is essential when planning pregnancy.

Energy expenditure in animal locomotion.

A wide variety of data on the energy expended by animals in running, flying, or swimming can be accounted for by the simple hypothesis that all animals require the same quantity of energy to carry a unit of their own body mass one "step." For running locomotion this is approximately 3 x 10(-4) calorie per gram per step.

Coastal stormwater wet pond sediment nitrogen dynamics.

Wet ponds are a common type of stormwater control measure (SCM) in coastal areas of the southeastern US, but their internal nitrogen dynamics have not been extensively studied. Using flow-through intact sediment core incubations, net sediment N2 fluxes before and after a nitrate addition from five wet ponds spanning a range of ages (3.25-10years old) were quantified through membrane inlet mass spectrometry during early summer. Multiple locations within a single wet pond (6.16years old) were also sampled during ambient conditions in late summer to determine the combined effects of depth, vegetation, and flow path position on net N2 fluxes at the sediment-water interface. All pond sediments had considerable rates of net nitrogen fixation during ambient conditions, and net N2 fluxes during nitrate-enriched conditions were significantly correlated with pond age. Following a nitrate addition to simulate storm conditions, younger pond sediments shifted towards net denitrification, but older ponds exhibited even higher rates of net nitrogen fixation. The pond forebay had significantly higher rates of net nitrogen fixation compared to the main basin, and rates throughout the pond were an order of magnitude higher than the early summer experiment. These results identify less than optimal nitrogen processing in this common SCM, however, data presented here suggest that water column mixing and pond sediment excavation could improve the capacity of wet ponds to enhance water quality by permanently removing nitrogen.

Effect of extended-duration thromboprophylaxis on venous thromboembolism and major bleeding among acutely ill hospitalized medical patients: a bivariate analysis.

Essentials Anticoagulants prevent venous thromboembolism but may be associated with greater bleeding risks. Bivariate analysis assumes a non-linear relationship between efficacy and safety outcomes. Extended full-dose betrixaban is favorable over standard enoxaparin in bivariate endpoint. Clinicians must weigh efficacy and safety outcomes in decision-making on thromboprophylaxis. SUMMARY: Background Among acutely ill hospitalized medical patients, extended-duration thromboprophylaxis reduces the risk of venous thromboembolism (VTE), but some pharmacologic strategies have been associated with greater risks of major bleeding, thereby offsetting the net clinical benefit (NCB). Methods To assess the risk-benefit profile of anticoagulation regimens, a previously described bivariate method that does not assume a linear risk-benefit tradeoff and can accommodate different margins for efficacy and safety was performed to simultaneously assess efficacy (symptomatic VTE) and safety (major bleeding) on the basis of data from four randomized controlled trials of extended-duration (30-46 days) versus standard-duration (6-14 days) thromboprophylaxis among 28 227 patients (EXCLAIM, ADOPT, MAGELLAN and APEX trials). Results Extended thromboprophylaxis with full-dose betrixaban (80 mg once daily) was superior in efficacy and non-inferior in safety to standard-duration enoxaparin, and showed a significantly favorable NCB, with a risk difference of - 0.51% (- 0.89% to - 0.10%) in the bivariate outcome. Extended enoxaparin was superior in efficacy and inferior in safety (bivariate outcome: 0.03% [- 0.37% to 0.43%]), whereas apixaban and rivaroxaban were non-inferior in efficacy and inferior in safety (- 0.20% [- 0.49% to 0.17%] and 0.23% [- 0.16% to 0.69%], respectively). Reduced-dose betrixaban did not show a significant difference in either efficacy or safety (0.41% [- 0.85% to 1.94%]). Conclusions In a bivariate analysis that assumes non-linear risk-benefit tradeoffs, extended prophylaxis with full-dose betrixaban was superior to standard-duration enoxaparin, whereas other regimens failed to simultaneously achieve both superiority and non-inferiority with respect to symptomatic VTE and major bleeding in the management of acutely ill hospitalized medical patients.

Metabolic activation of cyclopenta(cd)pyrene to 3,4-epoxycyclopenta(cd)pyrene by rat liver microsomes.

Cyclopenta(cd)pyrene (CPP), a polycyclic aromatic hydrocarbon without a bay region, is a potent bacterial mutagen. The experiments reported in this paper demonstrate that the major CPP metabolite generated by liver microsomes prepared from either phenobarbital or 3-methylcholanthrene pretreated rats is the optically active trans-3,4-dihydroxy-3,4-dihydrocyclopenta(cd)pyrene. Other experiments indicate that formation of the trans-3,4-dihydrodiol of CPP probably proceeds via enzymatic hydrolysis of 3,4-epoxycyclopenta(cd)pyrene by opening of the O--C(3) bond. (a) The racemic 3,4-epoxycyclopenta(cd)pyrene has been synthesized via the bromohydrin of CPP and shown to hydrolyze primarily to 3,4-dihydrocyclopenta(cd)pyrene-4-one and to mixtures of the trans- and cis-3,4-dihydrodiols. Detection of 3,4-dihydrocyclopenta(cd)pyrene-4-one as the major acid catalyzed rearrangement product indicates the opening of the epoxide at the C(3) position to yield a carbonium ion followed by an NIH shift. (b) The synthetic epoxide is potently mutagenic to bacteria with a similar spectrum of mutagenicity against Salmonella typhimurium strains carrying base-pair substitution or frameshift mutations as was seen with CPP in the presence of liver enzymes. These results indicate that 3,4-epoxycyclopenta(cd)pyrene is the major microsomal and mutagenic metabolite of CPP.

Binding parameters and idiotypic profile of the whole immunoglobulin and Fab' fragments of murine monoclonal antibody to distinct determinants of the human high molecular weight-melanoma associated antigen.

The nonspecific accumulation of radioactivity in bone marrow, liver, and spleen in patients with melanoma injected with radiolabeled whole IgG of anti-high molecular weight-melanoma associated antigen (HMW-MAA) monoclonal antibody (mAb) hampers the application of immunoscintigraphy to visualize melanoma lesions. This nonspecific background can be reduced by utilizing fragments which do not contain the Fc portion of anti-HMW-MAA mAb. Since the in vivo targeting to melanoma lesions of radiolabeled F(ab')2 and Fab' fragments of anti-HMW-MAA mAb is critically dependent on their binding parameters, we have analyzed the effect of fragmentation on the binding characteristics of the anti-HMW-MAA mAbs 225.28, 763.74, and TP41.2. The three mAbs recognize distinct and spatially distant determinants with a heterogeneous distribution on the pool of HMW-MAA molecules synthesized by melanoma cells. The determinant recognized by mAb TP41.2 is detectable on a markedly smaller population of HMW-MAA molecules than those recognized by mAbs 225.28 and 763.74. 125I-labeled F(ab')2 fragments of the three mAbs displayed an immunoreactive fraction similar to that of the whole IgG, while Fab' fragments displayed a lower one. Fragmentation of mAbs 225.28 and TP41.2 to F(ab')2 produced a 2- and 1.5-fold reduction in their association constants but did not cause a significant change in that of mAb 763.74. Cleavage of F(ab')2 fragments to Fab' fragments produced 2-, 40-, and 7-fold reductions in the association constants of mAbs 225.28, 763.74, and TP41.2, respectively. These changes qualitatively fit the predictions of theory for univalent and bivalent mAb binding, since mAbs 763.74 and TP41.2 appear to show bivalent binding to melanoma cells and mAb 225.28 to show univalent binding. The affinity constant of IgG, F(ab')2 and Fab' fragments of mAbs 225.28, 763.74, and TP41.2 displays an inverse relationship with the extent of their time-dependent release from the membrane of melanoma cells. Since no endocytosis of mAb could be detected, the latter results suggest that radioactivity remains bound to melanoma cells in vivo for a longer time following injection of F(ab')2 fragments than following that of Fab' fragments of each of the anti-HMW-MAA mAb tested. Radiolabeled Fab' fragments of mAbs 763.74 and TP41.2 displayed a marked reduction in their reactivity with some of the antiidiotypic mAb tested. The loss of some idiotopes is likely to be caused by changes in the conformation of the molecules associated with the fragmentation of IgG and by damage during the iodination procedure.

Morphological transformation and DNA adduct formation by benz[j]aceanthrylene and its metabolites in C3H10T1/2CL8 cells: evidence for both cyclopenta-ring and bay-region metabolic activation pathways.

Benz[j]aceanthrylene (B[j]A), a cyclopenta-fused polycyclic aromatic hydrocarbon related to 3-methylcholanthrene, has been studied to identify the major routes of metabolic activation in transformable C3H10T1/2CL8 (C3H10T1/2) mouse embryo fibroblasts in culture. Previous studies have reported that the major (55% of total) B[j]A metabolite formed by C3H10T1/2 cells was (+/-)-trans-9,10-dihydro-9,10-dihydroxy-B[j]A (B[j]A-9,10-diol), the dihydrodiol in the bay-region ring, with moderate amounts (14% of total) of (+/-)-trans-1,2-dihydro-1,2-dihydroxy-B[j]A (B[j]A-1,2-diol), the cyclopenta-ring dihydrodiol. The morphological transforming activities of three potential intermediates formed by metabolism of B[j]A by C3H10T1/2 cells, (+/-)-anti-trans-9,10-dihydro-9,10-dihydroxy-B[j]A-7,8-oxide (B[j]A-diol-epoxide), B[j]A-9,10-oxide, and B[j]A-1,2-oxide as well as the two B[j]A-dihydrodiols were examined. B[j]A, B[j]A-diol-epoxide, B[j]A-1,2-oxide, and B[j]A-9,10-diol were found to have moderate to strong activities with B[j]A-diol-epoxide the most active compared to B[j]A, while B[j]A-1,2-diol was inactive. B[j]A-9,10-oxide was found to be a weak transforming agent. At 0.5 microgram/ml, the following percentage of dishes with type II or III foci were observed: B[j]A, 59%; B[j]A-diol-epoxide, 75%; B[j]A-1,2-oxide, 25%; and B[j]A-9,10-diol, 17%. DNA adducts of B[j]A, B[j]A-9,10-diol, B[j]A-diol-epoxide, B[j]A-9,10-oxide, and B[j]A-1,2-oxide in C3H10T1/2 cells were isolated, separated, identified, and quantitated using the 32P-postlabeling method. B[j]A forms two major groups of adducts: one group of adducts is the result of the interaction of B[j]A-1,2-oxide with 2'-deoxyguanosine and 2'-deoxyadenosine; the second group of adducts is a result of the interaction of B[j]A-diol-epoxide with 2'-deoxyguanosine and 2'-deoxyadenosine. Qualitative and quantitative analysis of the postlabeling data suggests that B[j]A is metabolically activated by two distinct routes, the bay-region diol-epoxide route and the cyclopenta-ring oxide route, the former being the most significant.

Mutagenesis and morphological transformation of mammalian cells by a non-bay-region polycyclic cyclopenta(cd)pyrene and its 3,4-oxide.

Cyclopenta(cd)pyrene, a constituent of environmental emissions, has been found to mutate and transform mammalian cells in culture. Cyclopenta(cd)pyrene 3,4-oxide, a presumed metabolite, was found to be a direct-acting mutagen and to transform mammalian cells. These results suggest that cyclopenta(cd)pyrene 3,4-oxide may be an ultimate mutagenic form of the parent hydrocarbon.

Evaluation of Basal Serum or Plasma Cortisol Concentrations for the Diagnosis of Hypoadrenocorticism in Dogs.

BACKGROUND: Previous studies that included limited numbers of affected dogs have suggested basal cortisol concentrations ≤55 nmol/L (2 µg/dL) are sensitive, but nonspecific, for a diagnosis of hypoadrenocorticism. A detailed assessment of the diagnostic utility of basal cortisol concentrations is warranted. HYPOTHESIS/OBJECTIVES: To evaluate the utility of basal cortisol concentrations for the diagnosis of hypoadrenocorticism in a large number of dogs, including those with and without serum electrolyte abnormalities. ANIMALS: Five hundred and twenty-two dogs, including 163 dogs with hypoadrenocorticism, 351 dogs with nonadrenal gland illness, and 8 dogs with equivocal results. METHODS: Retrospective study. Basal and post-ACTH cortisol concentrations and sodium and potassium concentrations were collected from medical records. A receiver operating characteristic (ROC) curve was constructed for basal cortisol concentrations by standard methodologies. Sensitivity, specificity, and predictive values were determined for various cut-points. RESULTS: The area under the ROC curve was 0.988 and was similarly excellent regardless of serum electrolyte concentrations. At the most discriminatory cut-point of 22 nmol/L (0.8 µg/dL), sensitivity and specificity were 96.9 and 95.7%, respectively. A basal cortisol concentration of ≤55 nmol/L (2 µg/dL) resulted in a sensitivity of 99.4%. Conversely, a basal cortisol concentration of ≤5.5 nmol/L (0.19 µg/dL) resulted in a specificity of 99.1%. CONCLUSIONS AND CLINICAL IMPORTANCE: Similar to findings in previous studies, basal cortisol concentrations >55 nmol/L (2 µg/dL) are useful in excluding a diagnosis of hypoadrenocorticism. Interestingly, excellent specificities and positive predictive values were observed at lower cut-point cortisol concentrations.

In situ ground water denitrification in stratified, permeable soils underlying riparian wetlands.

The ground water denitrification capacity of riparian zones in deep soils, where substantial ground water can flow through low-gradient stratified sediments, may affect watershed nitrogen export. We hypothesized that the vertical pattern of ground water denitrification in riparian hydric soils varies with geomorphic setting and follows expected subsurface carbon distribution (i.e., abrupt decline with depth in glacial outwash vs. negligible decline with depth in alluvium). We measured in situ ground water denitrification rates at three depths (65, 150, and 300 cm) within hydric soils at four riparian sites (two per setting) using a 15N-enriched nitrate "push-pull" method. No significant difference was found in the pattern and magnitude of denitrification when grouping sites by setting. At three sites there was no significant difference in denitrification among depths. Correlations of site characteristics with denitrification varied with depth. At 65 cm, ground water denitrification correlated with variables associated with the surface ecosystem (temperature, dissolved organic carbon). At deeper depths, rates were significantly higher closer to the stream where the subsoil often contains organically enriched deposits that indicate fluvial geomorphic processes. Mean rates ranged from 30 to 120 microg N kg(-1) d(-1) within 10 m versus <1 to 40 microg N kg(-1) d(-1) at >30 m from the stream. High denitrification rates observed in hydric soils, down to 3 m within 10 m of the stream in both alluvial and glacial outwash settings, argue for the importance of both settings in evaluating the significance of riparian wetlands in catchment-scale N dynamics.

Cortical blindness and cerebral infarction associated with severe hypoglycemia.

OBJECTIVE: To describe a case of cortical blindness and cerebral infarction associated with severe hypoglycemia. CONCLUSIONS: The possible pathogenesis of the neurological defects is discussed.