Meta-analysis of the effects of sulfate versus hydroxy trace mineral source on nutrient digestibility in dairy and beef cattle.

Trace mineral (TM) source can potentially alter nutrient digestibility through effects on microbial populations. A meta-analysis was conducted to determine whether sulfate versus hydroxy (IntelliBond) sources of supplemental Cu, Zn, and Mn had any effect on dry matter intake (DMI), dry matter digestibility, and neutral detergent fiber (NDF) digestibility. All available cattle studies (8 studies, 12 comparisons) were used to estimate the effect size (hydroxy mean - sulfate mean). Factors included in the analysis were method of digestibility analysis (total collection, marker-based, or 24 h in situ), study design (randomized design or Latin square), beef (n = 5) versus dairy (n = 7) cattle, and days on treatment; these factors were retained when P < 0.05. Dry matter digestibility was increased by hydroxy TM in beef (1.64 ± 0.35 units) but not in dairy models (0.16 ± 0.13 units) relative to sulfate TM. The NDF digestibility increased significantly with hydroxy versus sulfate TM, but digestibility assessment method influenced this response. Studies using total collection or undigested NDF as a flow marker showed a significant increase (2.68 ± 0.40 units and 1.08 ± 0.31 units, respectively) in NDF digestibility for hydroxy versus sulfate TM; but studies utilizing 24-h in situ incubation did not detect any change (-0.03 ± 0.23 units). These observations may reveal differences in precision of measurement or may indicate mineral effects beyond the rumen; total collection is considered the gold standard method. Hydroxy TM did not affect DMI per animal or per unit of body weight relative to sulfate TM. In conclusion, feeding hydroxy versus sulfate TM does not appear to affect DMI but, depending on type of cattle and method of measurement, can increase dry matter digestibility and NDF digestibility, which may be explained by differences in solubility of the TM sources in rumen, differentially affecting fermentation.

Impact of a physician - critical care practitioner pre-hospital service in Wales on trauma survival: a retrospective analysis of linked registry data.

The Emergency Medical Retrieval and Transfer Service for Wales launched in 2015. This service delivers senior pre-hospital doctors and advanced critical care practitioners to the scene of time-critical life- and limb-threatening incidents to provide advanced decision-making and pre-hospital clinical care. The impact of the service on 30-day mortality was evaluated retrospectively using a data linkage system. The study included patients who sustained moderate-to-severe blunt traumatic injuries (injury severity score ≥ 9) between 27 April 2015 and 30 November 2018. The association between pre-hospital management by the Emergency Medical Retrieval and Transfer Service and 30-day mortality was assessed using multivariable logistic regression. In total, data from 4035 patients were analysed, of which 412 (10%) were treated by the Emergency Medical Retrieval and Transfer Service. A greater proportion of patients treated by the Emergency Medical Retrieval and Transfer Service had an injury severity score ≥ 16 and Glasgow coma scale ≤ 12 (288 (70%) vs. 1435 (40%) and 126 (31%) vs. 325 (9%), respectively). The unadjusted 30-day mortality rate was 11.7% for patients managed by the Emergency Medical Retrieval and Transfer Service compared with 9.6% for patients managed by standard pre-hospital care services. However, after adjustment for differences in case-mix, the 30-day mortality rate for patients treated by the Emergency Medical Retrieval and Transfer Service was 37% lower (adjusted odds ratio 0.63 (95%CI 0.41-0.97); p = 0.037). The introduction of an emergency medical retrieval service was associated with a reduction in 30-day mortality for patients with blunt traumatic injury.

Prenatal tobacco smoke exposure and neurological impairment at 10 years of age among children born extremely preterm: a prospective cohort.

OBJECTIVE: To determine the association between prenatal tobacco smoke exposure and neurological impairment at 10 years of age among children born extremely preterm (<28 weeks of gestation). DESIGN: The Extremely Low Gestational Age Newborn (ELGAN) Study, a prospective cohort. SETTING: Ten-year follow-up of extremely preterm infants born at 14 US hospitals between 2002 and 2004. METHODS: Prenatal tobacco smoke exposure was defined as a mother's report at enrolment of active (i.e. maternal) and passive smoking during pregnancy. Poisson regression with generalized estimating equations was used. Models adjusted for mother's age, race/ethnicity, education, insurance, pre-pregnancy body mass index, US region, multiple gestation and infant's sex; and in sensitivity analysis, gestational age at delivery and clinical subtype of preterm birth, given their classification as intermediate and non-confounding variables. MAIN OUTCOMES: Neurological impairment at 10 years, epilepsy, cerebral palsy and cognitive impairment. RESULTS: Of 1200 ELGAN study survivors, 856 were assessed at 10 years of age with neurological outcomes, of whom 14% (118/856) had active tobacco exposure during pregnancy and 24% (207/852) had passive tobacco exposure. Compared with children who were not exposed prenatally to tobacco, children exposed to active tobacco use during pregnancy had a higher risk of epilepsy (14% versus 5%; adjusted relative risk: 1.68, 95% CI 1.45-1.92). This risk remained after adjustment for gestational age at delivery and clinical subtype of preterm birth. Prenatal tobacco smoke exposure was not associated with other assessed neurological outcomes, including cerebral palsy and multiple measures of cognitive impairment. CONCLUSIONS: Among children born extremely preterm, prenatal active tobacco smoke exposure was associated with an increased risk of epilepsy at 10 years of life. TWEETABLE ABSTRACT: Among infants born before 28 weeks of gestation, prenatal active tobacco smoke exposure was associated with an increased risk of epilepsy at 10 years of life.

Effects of copper hydroxychloride on growth performance and abundance of genes involved in lipid metabolism of growing pigs.

An experiment was conducted to test the hypothesis that copper (Cu) hydroxychloride improves growth performance by upregulating the mRNA transcription of genes involved in lipid metabolism of pigs fed a diet based on corn, soybean meal (SBM), and distillers dried grains with solubles (DDGS). Thirty-two pigs (15.05 ± 0.98 kg) were allotted to 2 dietary treatments with 2 pigs per pen for a total of 8 replicate pens per treatment. Pigs were fed a corn-SBM-DDGS control diet that included Cu to meet the requirement. A second diet was formulated by adding 150 mg Cu/kg from copper hydroxychloride to the control diet. On the last day of the experiment, one pig per pen was sacrificed, and samples from liver, skeletal muscle, and subcutaneous adipose tissue were collected to analyze relative mRNA abundance of genes involved in lipid metabolism. Results indicated that overall ADG and G:F were greater (P < 0.05) for pigs fed the diet containing copper hydroxychloride compared with pigs fed the control diet. Pigs fed the diet supplemented with copper hydroxychloride also had increased (P < 0.05) abundance of cluster of differentiation 36 in the liver and increased (P < 0.05) abundance of fatty acid-binding protein 4 and lipoprotein lipase in subcutaneous adipose tissue. Inclusion of copper hydroxychloride also tended to increase (P < 0.10) the abundance of fatty acid-binding protein 1, peroxisome proliferator-activated receptor α, and carnitine palmitoyltransferase 1B in the liver, skeletal muscle, and subcutaneous adipose tissue, respectively. This indicates that dietary Cu may affect signaling pathways associated with lipid metabolism by improving the uptake, transport, and utilization of fatty acids. In conclusion, supplementation of copper hydroxychloride to the control diet improved growth performance and upregulated the abundance of some genes involved in postabsorptive metabolism of lipids.

Lipid metabolic differences in cows producing small or large milk fat globules: Fatty acid origin and degree of saturation.

This study compared cows that consistently produce milk with small (volume-weighted mean diameter of 2.92-3.83 µm, with an average diameter of 3.29 µm) or large (volume-weighted mean diameter of 4.58-5.67 µm, with an average diameter of 4.92 µm) milk fat globule (MFG) size distributions in terms of the fatty acid (FA) composition of the MFG core. Selected cows fell into the respective size group over at least 3 independent measurements, including an observation period before the experiment. Further selection criteria were similar milk production traits between cows (milk yield, fat yield, fat/protein ratio) and established lactation (>50 d in milk). However, the selected groups differed in parity (parity 1-3 and 3-5 in the small and large MFG groups, respectively), and the small MFG group was an average of 25 d in milk later in their lactation period. All cows were under the same nutritional management and environmental conditions. Here, we show that cows with the small or large MFG phenotype differed in their lipid metabolism in terms of the FA composition of the MFG core. Our results indicate that cows with the small MFG phenotype produced milk with higher concentrations of unsaturated FA despite being fed the same diet. We suggest that this characteristic of the small MFG phenotype is the result of increased uptake of long-chain FA from the blood circulation. A relationship between the degree of unsaturation and MFG size was also identified in preliminary studies across other species-namely, camels, sheep, and goats. These findings show the potential for on-farm selection of cows (and potentially other dairy species) based on MFG size to produce milk with improved nutrient composition. This could lead to purpose-specific separation of milk based on MFG size and FA profile, both known to alter the technological properties of milk.

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.

Effects of copper hydroxychloride and distillers dried grains with solubles on intestinal microbial concentration and apparent ileal and total tract digestibility of energy and nutrients by growing pigs1.

An experiment was conducted to test the hypothesis that Cu hydroxychloride improves nutrient digestibility and alters the concentration of microbial protein in the small intestine or large intestine by pigs fed a corn-soybean meal diet or a diet based on corn, soybean meal, and distillers dried grains with solubles (DDGS). Twenty-four barrows (33.3 ± 3.4 kg) that had a T-cannula installed in the distal ileum were allotted to a 2 × 2 factorial design with 2 levels of DDGS (0% or 45%) and 2 levels of supplemental Cu from Cu hydroxychloride (0 or 150 mg/kg). A 2-period switch back design with the 4 diets and 6 replicate pigs per diet in each period was used resulting in 12 replicate pigs per diet for the 2 periods. The initial 9 d of each period was considered an adaptation period to the experimental diets. For each period, feces were collected on days 10, 11, and 12, and ileal digesta were collected for 8 h on days 13 and 14. Results indicated that inclusion of 45% DDGS to diets reduced (P < 0.05) the apparent ileal digestibility (AID) of AA and the AID and the apparent total tract digestibility (ATTD) of dry matter, gross energy, and crude protein. In contrast, inclusion of DDGS to diets increased (P < 0.05) the AID and the ATTD of acid hydrolyzed ether extract and the concentration of microbial protein in the hindgut (P < 0.05). However, the total concentration of volatile fatty acids (VFA) in ileal digesta and in feces from pigs fed the DDGS diets were not different from concentrations in pigs fed diets without DDGS. The AID and ATTD of dry matter, gross energy, and crude protein were not affected by dietary Cu concentrations, but the AID and ATTD of acid hydrolyzed ether extract were greater (P < 0.05) in diets supplemented with Cu hydroxychloride compared with diets without Cu hydroxychloride. There was also a reduction (P < 0.05) in the concentration of microbial protein and a tendency for a reduction (P < 0.10) in the total concentration of VFA in feces when diets were supplemented with Cu hydroxychloride. In conclusion, supplementation of Cu hydroxychloride to diets improved AID and ATTD of acid hydrolyzed ether extract and reduced the concentration of microbial protein in the large intestine and this effect was observed in diets containing DDGS as well as in diets without DDGS.

Cadmium body burden and increased blood pressure in middle-aged American Indians: the Strong Heart Study.

Cadmium (Cd) is an environmental pollutant that has been associated with cardiovascular disease in populations, but the relationship of Cd with hypertension has been inconsistent. We studied the association between urinary Cd concentrations, a measure of total body burden, and blood pressure in American Indians, a US population with above national average Cd burden. Urinary Cd was measured using inductively coupled plasma mass spectrometry, and adjusted for urinary creatinine concentration. Among 3714 middle-aged American Indian participants of the Strong Heart Study (mean age 56 years, 41% male, 67% ever-smokers, 23% taking antihypertensive medications), urinary Cd ranged from 0.01 to 78.48 µg g-1 creatinine (geometric mean=0.94 µg g-1) and it was correlated with smoking pack-year among ever-smokers (r2=0.16, P<0.0001). Participants who were smokers were on average light-smokers (mean 10.8 pack-years), and urinary Cd was similarly elevated in light- and never-smokers (geometric means of 0.88 µg g-1 creatinine for both categories). Log-transformed urinary Cd was significantly associated with higher systolic blood pressure in models adjusted for age, sex, geographic area, body mass index, smoking (ever vs never, and cumulative pack-years) and kidney function (mean blood pressure difference by lnCd concentration (ß)=1.64, P=0.002). These associations were present among light- and never-smokers (ß=2.03, P=0.002, n=2627), although not significant among never-smokers (ß=1.22, P=0.18, n=1260). Cd was also associated with diastolic blood pressure among light- and never-smokers (ß=0.94, P=0.004). These findings suggest that there is a relationship between Cd body burden and increased blood pressure in American Indians, a population with increased cardiovascular disease risk.

Copper hydroxychloride improves growth performance and reduces diarrhea frequency of weanling pigs fed a corn-soybean meal diet but does not change apparent total tract digestibility of energy and acid hydrolyzed ether extract.

Three experiments were conducted to determine effects of Cu hydroxychloride on DE and ME, apparent total tract digestibility (ATTD) of energy and acid hydrolyzed ether extract (AEE), and growth performance of pigs fed a diet based on corn and soybean meal (SBM). In Exp. 1, 80 weanling pigs (6.80 ± 1.69 kg) were allotted to 2 treatments with 4 pigs per pen and 10 pen replicates per diet. Pigs were fed a corn-SBM control diet that had Cu added to meet the requirement. A second diet was formulated by adding 150 mg Cu/kg from Cu hydroxychloride to the control diet. Both diets were fed for 4 wk. Results indicated that ADG, G:F, and final BW were greater ( ≤ 0.05) and fecal scores were reduced ( ≤ 0.05) for pigs fed the diet containing150 mg Cu/kg as hydroxychloride compared with pigs fed the control diet. In Exp. 2, 36 barrows (9.89 ± 1.21 kg) were randomly allotted to 3 dietary treatments and placed in metabolism crates. The control diet was based on corn and SBM and contained 20 mg Cu/kg. Two additional diets were formulated by adding 100 or 200 mg Cu/kg from Cu hydroxychloride to the control diet. Diets were fed for 28 d, with feces and urine being collected from d 9 to 14, d 16 to 21, and d 23 to 28. The DE and ME of diets and the ATTD of GE and AEE were not affected by dietary Cu concentrations, but increased ( < 0.01) by collection period. In Exp. 3, 150 pigs (10.22 ± 1.25 kg) were fed the same 3 diets as used in Exp. 2. Diets were provided on an ad libitum basis for 4 wk. Fecal scores were recorded, and on the last day of the experiment, blood samples were collected and tumor necrosis factor-α (TNF-α), IgA, blood urea N, total protein, and albumin were measured. Phase 1 ADG and G:F and final BW on d 28 were greater ( ≤ 0.05) for pigs fed diets containing 100 or 200 mg Cu/kg supplemented by Cu hydroxychloride compared with pigs fed the control diet. Pigs fed the diets supplemented with Cu hydroxychloride also had reduced ( ≤ 0.05) overall fecal scores and diarrhea frequency compared with pigs fed the control diet. However, no differences among treatments were observed for concentrations of TNF-α, IgA, blood urea N, total protein, or albumin. In conclusion, supplementation of Cu as Cu hydroxychloride to diets fed to weanling pigs improved growth performance and reduced diarrhea frequency, but this did not appear to be a result of increased digestibility of energy or AEE.

Inflammation in induced sputum after aluminium oxide exposure: an experimental chamber study.

INTRODUCTION: Workers in aluminium production are exposed to a complex mixture of particles and gases potentially harmful to the airways, among them aluminium oxide (Al2O3). With the use of an exposure chamber, we aimed to examine the effects of short-term controlled exposure to Al2O3 on lung function and inflammatory markers in healthy volunteers. METHODS: 15 men (age 19-31) were exposed in random order to clean air or Al2O3 particles (3.8-4.0 mg/m(3)) for 2 h including 30 min exercise (stationary bike, 75 W). The permissible exposure level (PEL) for Al2O3 by Occupational Safety and Health Administration, USA, is 5 mg/m(3) time weighted average (TWA). Sham and particle exposures were separated by at least 2 weeks. Spirometry was carried out, and induced sputum and blood samples were collected 48 h before and 4 and 24 h after exposure. RESULTS: Levels of sputum neutrophils (mean (±SEM)) was increased 24 h post-Al2O3 vs pre-Al2O3 exposure (43% (4) vs 31% (4), p=0.01) and the protein level of interleukin (IL)-8 had a 4.8 (0.9)-fold change increase 24 h after exposure (p<0.01). Following Al2O3 exposure, gene signatures in sputum were significantly increased related to several pathways. CONCLUSIONS: The present study suggests that controlled exposure to Al2O3 particles at levels below PEL (TWA) induces airway inflammation in healthy humans marked by elevated neutrophils and elevated IL-8. In addition, increased expression of genes associated with several biological processes was observed in sputum. Interestingly, inhaled Al2O3-induced effects were localised to the airways and not systemic.

Developmental Windows of Susceptibility to Inorganic Arsenic: A Survey of Current Toxicologic and Epidemiologic Data.

Globally, millions of people are exposed to elevated levels of inorganic arsenic (iAs) via drinking water. Exposure to iAs is associated with a wide range of negative health outcomes, including cancers, skin lesions, neurological impairment, cardiovascular diseases, and an increased susceptibility to infection. Among those exposed to iAs, the developing fetus and young children represent particularly sensitive subpopulations. Specifically, it has been noted in animal models and human populations that prenatal and early life iAs exposures are associated with diseases occurring during childhood and later in life. Recent epidemiologic and toxicologic studies have also demonstrated that epigenetic alterations may play a key mechanistic role underlying many of the iAs-associated health outcomes, including the carcinogenic and immunologic effects of exposure. This review summarizes some of the key studies related to prenatal and early life iAs exposure and highlights the complexities in isolating the precise developmental windows of exposure associated with these health outcomes.

Rapid sequence induction.

Emergency tracheal intubation undertaken by Rapid sequence induction (RSI) is a fundamental component of military anaesthesia. This common emergency procedure has evolved in both civilian and military practice, since it was first described, as new drugs have become available. Current practice now differs significantly from that undertaken by the procedure's initial advocates. This is particularly the case in the deployed military environment. As military medicine continues to improve injury survivability, RSI will be undertaken in increasingly unstable casualties, requiring a bespoke emergency induction not commonly practised in the civilian setting.

Effect of dietary copper amount and source on copper metabolism and oxidative stress of weanling pigs in short-term feeding.

Forty-eight weanling barrows were used to determine the effects of amount and source of dietary Cu on Cu metabolism, oxidative stress in the duodenum, and VFA ratios in the cecum of weanling pigs in short-term feeding. At 21 d of age, newly weaned pigs were stratified by BW (7.03 ± 1.20 kg) and equally assigned to 1 of the following dietary treatments: 1) control (5 mg supplemental Cu/kg diet from CuSO4), 2) 225 mg supplemental Cu/kg diet from CuSO4, or 3) 225 mg supplemental Cu/kg diet from tribasic Cu chloride (TBCC). Pigs were housed 2 pigs per pen and were fed a complex diet until harvest on d 11 and 12. During harvest, bile and liver were obtained for mineral analysis, and liver samples were obtained for analysis of mRNA expression of Cu regulatory proteins. Digesta of duodenum, proximal jejunum, and ileum were collected for soluble Cu analysis. Mucosal scrapings of duodenum, proximal jejunum, and ileum were obtained for analysis of mucosal Cu concentration and mRNA expression of Cu regulatory proteins. Duodenal mucosal scrapings were also collected for analysis of malondialdehyde (MDA). Pigs fed high Cu had markedly greater (P < 0.0001) Cu concentrations in the duodenal, proximal jejunal, and ileal mucosa than controls. Copper in the duodenal mucosa was greater (P = 0.003) in CuSO4 than TBCC pigs. Duodenal MDA concentrations were greater (P = 0.003) in CuSO4 vs. control pigs and tended (P = 0.06) to be greater than in TBCC pigs. Duodenal antioxidant 1 (Atox1) mRNA was downregulated (P < 0.01) in pigs fed high Cu compared to controls and was not affected by Cu source. Compared with control pigs, those fed CuSO4 and TBCC had greater (P < 0.001) liver and bile Cu concentrations. Liver Cu was also greater (P = 0.0007) in TBCC than CuSO4-fed pigs. Hepatic Cu transporting ß-polypeptide ATPase (Atp7b) was upregulated (P = 0.02) in the Cu-supplemented pigs compared with controls and did not differ among Cu sources. The acetate:propionate ratio in cecal contents was much greater in pigs supplemented with 225 mg Cu/kg diet than in controls. When fed at 225 mg Cu/kg diet, TBCC may cause less oxidative stress in the duodenum than CuSO4. Feeding weanling pigs increased Cu resulted in modulation of duodenal and liver at the transcription level.

A retrospective survey of substance abuse in anaesthetists in Australia and New Zealand from 2004 to 2013.

A questionnaire on substance abuse was distributed electronically to the heads of 185 Australian and New Zealand College of Anaesthetists accredited anaesthesia departments in Australia and New Zealand. The response rate was 57%. From January 2004 to December 2013, 61 cases of substance abuse were identified, giving an estimated incidence of 1.2 cases per 1000 anaesthetist years. Of 44 detailed reports completed, the majority were aged between 30 and 49 years, were male and of specialist grade. However, when corrected for gender and grade, the estimated overall incidence was higher in females and twice as high for trainees compared with specialists. When compared with prior surveys, the pattern of substance abuse in Australia and New Zealand appears to have changed significantly, with a notable increase in propofol and alcohol abuse and a decrease in reported cases of opioid abuse. Common presenting features of abuse included intoxication and witnessed abuse. Seventy percent of cases had more than one comorbid condition, most frequently either mental health or family problems. Only 32% of abusers had made a long-term recovery within the specialty. Death was the eventual outcome in 18% overall, with a particularly high mortality associated with propofol abuse (45%). Trainee suicide from all causes was reported at three times the rate of specialists. The findings indicate that substance abuse remains a significant problem in Australia and New Zealand and is associated with a significant mortality rate.