Measurements of Production Properties of K0S mesons and Lambda hyperons in Proton-Carbon Interactions at 31 GeV/c

Spectra of K0S mesons and Λ hyperons were measured in p+C interactions at 31 GeV/c with the large acceptance NA61/SHINE spectrometer at the CERN SPS. The data were collected with an isotropic graphite target with a thickness of 4% of a nuclear interaction length. Interaction cross sections, charged pion spectra, and charged kaon spectra were previously measured using the same data set. Results on K0S and Λ production in p+C interactions serve as reference for the understanding of the enhancement of strangeness production in nucleus-nucleus collisions. Moreover, they provide important input for the improvement of neutrino flux predictions for the T2K long baseline neutrino oscillation experiment in Japan. Inclusive production cross sections for K0S and Λ are presented as a function of laboratory momentum in intervals of the laboratory polar angle covering the range from 0 up to 240 mrad. The results are compared with predictions of several hadron production models. The K0S mean multiplicity in production processes and the inclusive cross section for K0S production were measured and amount to 0.127 ± 0.005 (stat) ± 0.022 (sys) and 29.0 ± 1.6 (stat) ± 5.0 (sys) mb, respectively.

The cyclotron production and nuclear imaging of bromine-77

In this investigation, bromine-77 was produced with a medical cyclotron and imaged with gamma cameras. Br-77 emits a 240 kev photon with a half life of 56 hours. The C-Br bond is stronger than the C-I bond and bromine is not collected in the thyroid. Bromine can be used to label many organic molecules by methods analogous to radioiodination. The only North American source of Br-77 in the 70's and 80's was Los Alamos National Laboratory, but it discontinued production in 1989. In this method, a p,3n reaction on Br-77 produces Kr-77 which decays with a 1.2 hour half life to Br-77. A cyclotron generated 40 MeV proton beam is incident on a nearly saturated NaBr or LiBr solution contained in a copper or titanium target. A cooling chamber through which helium gas is flowed separates the solution from the cyclotron beam line. Helium gas is also flowed through the solution to extract Kr-77 gas. The mixture flows through a nitrogen trap where Kr-77 freezes and is allowed to decay to Br-77. Eight production runs were performed, three with a copper target and five with a titanium target with yields of 40, 104, 180, 679, 1080, 685, 762 and 118 uCi respectively. Gamma ray spectroscopy has shown the product to be very pure, however corrosion has been a major obstacle, causing the premature retirement of the copper target. Phantom and in-vivo rat nuclear images, and an autoradiograph in a rat are presented. The quality of the nuclear scans is reasonable and the autoradiograph reveals high isotope uptake in the renal parenchyma, a more moderate but uniform uptake in pulmonary and hepatic tissue, and low soft tissue uptake. There is no isotope uptake in the brain or the gastric mucosa. ^

IMMUNOLOGICAL AND CYTOLOGICAL INVESTIGATION OF GAMMA INTERFERON PRODUCTION IN HUMAN T-LYMPHOCYTES INDUCED BY PMA AND PHA (IMMUNOGOLD, CELL CYCLE ANALYSIS)

The present study examined cellular mechanisms involved in the production and secretion of human (gamma)IFN. The hypothesis of this investigation was that (gamma)IFN is an export glycoprotein whose synthesis in human T lymphocytes is dependent on membrane stimulation, polypeptide synthesis in the rough endoplasmic reticulum, packaging in the Golgi complex, and release from the cell by exocytosis.^ The model system for this examination utilized T lymphocytes from normal donors and patients with chronic lymphocytic leukemia (CLL) induced in vitro with the tumor promoter, phorbol 12-myristate 13-acetate (PMA) and the lectin, phytohemagglutinin (PHA) to produce (gamma)IFN. This study reconfirmed the ability of PMA and PHA to synergistically induce (gamma)IFN production in normal T lymphocytes, as measured by viral inhibition assays and radio-immunoassays for (gamma)IFN. The leukemic T cells were demonstrated to produce (gamma)IFN in response to treatment with PHA. PMA treatment also induced (gamma)IFN production in the leukemic T cells, which was much greater than that observed in similarly treated normal T cells. In these same cells, however, combined treatment of the agents was shown to be ineffective at inducing (gamma)IFN production beyond the levels stimulated by the individual agents. In addition, the present study reiterated the synergistic effect of PMA/PHA on the stimulation of growth kinetics in normal T cells. The cell cycle of the leukemic T cells was also responsive to treatment with the agents, particularly with PMA treatment. A number of morphological alterations were attributed to PMA treatment including the acquisition of an elongated configuration, nuclear folds, and large cytoplasmic vacuoles. Many of the effects were observed to be reversible with dilution of the agents, and reversion to this state occurred more rapidly in the leukemic T cells. Most importantly, utilization of a thin section immuno-colloidal gold labelling technique for electron microscopy provided, for the first time, direct evidence of the cellular mechanism of (gamma)IFN production and secretion. The results of this latter study support the idea that (gamma)IFN is produced in the rough endoplasmic reticulum, transferred to the Golgi complex for accumulation and packaging, and released from the T cells by exocytosis. ^

Health literacy builds resilience among individuals and communities

Health is created in the context of everyday life, and health literacy originates in and helps shape the sociocultural context in which people live. Empowerment, equity, co-production and cultural capital have been shown to be positively associated with people’s health.

Effect of synthetic agonists of toll-like receptor 9 on canine lymphocyte proliferation and cytokine production in vitro.

Synthetic agonists of TLR9 containing novel DNA structures and R'pG (wherein R=1-(2'-deoxy-beta-d-ribofuranosyl)-2-oxo-7-deaza-8-methyl-purine) motifs, referred to as immune modulatory oligonucleotides (IMOs), have been shown to stimulate T(H)-1-type-immune responses and potently reverse allergen-induced T(H)-2 responses to T(H)-1 responses in vitro and in vivo in mice. In order to investigate the immunomodulatory potential of IMOs in dogs, canine peripheral blood mononuclear cells (PBMC) from healthy dogs were stimulated with three different IMOs and a control IMO, alone or in combination with concanavalin A (ConA). Lipopolysaccharide (LPS) was used as a positive control for B lymphocyte activation. Carboxyfluorescein diacetate succinimidyl ester and phenotype staining was used to tag proliferating T and B lymphocytes (CD5(+) and CD21(+)) by flow cytometry. Real-time PCR and ELISA were processed to assay cytokine production of IFN-gamma, IL-10, TGF-beta, IL-6 and IL-10. Like LPS, IMOs alone induced neither proliferation of CD5(+) T cells nor CD21(+) B cells, but both LPS and IMO had the capacity to co-stimulate ConA and induced proliferation of B cells. In combination with ConA, one of the IMOs (IMO1) also induced proliferation of T cells. IMO1 also significantly enhanced the expression of IFN-gamma on the mRNA and protein level in canine PBMC, whereas expression of IL-10, TGF-beta and IL-4 mRNAs was not induced by any of the IMOs. These results indicate that in canine PBMC from healthy dogs, IMO1 was able to induce a T(H)-1 immune response including T- and B-cell proliferation.

Complete digital workflow for the production of implant-supported single-unit monolithic crowns.

OBJECTIVES The aim of this case series was to introduce a complete digital workflow for the production of monolithic implant crowns. MATERIAL AND METHODS Six patients were treated with implant-supported crowns made of resin nano ceramic (RNC). Starting with an intraoral optical scan (IOS), and following a CAD/CAM process, the monolithic crowns were bonded either to a novel prefabricated titanium abutment base (group A) or to a CAD/CAM-generated individualized titanium abutment (group B) in premolar or molar sites on a soft tissue level dental implant. Economic analyses included clinical and laboratory steps. An esthetic evaluation was performed to compare the two abutment-crown combinations. RESULTS None of the digitally constructed RNC crowns required any clinical adaptation. Overall mean work time calculations revealed obvious differences for group A (65.3 min) compared with group B (86.5 min). Esthetic analysis demonstrated a more favorable outcome for the prefabricated bonding bases. CONCLUSIONS Prefabricated or individualized abutments on monolithic RNC crowns using CAD/CAM technology in a model-free workflow seem to provide a feasible and streamlined treatment approach for single-edentulous space rehabilitation in the posterior region. However, RNC as full-contour material has to be considered experimental, and further large-scale clinical investigations with long-term follow-up observation are necessary.

Estrogen induces nitric oxide production via nitric oxide synthase activation in endothelial cells.

INTRODUCTION 17β-estradiol (E2) has been found to induce vasodilation in the cardiovascular system and at physiological levels, resulting in prevention of cerebral vasospasm following subarachnoid hemorrhage (SAH) in animal models. The goal of this study was to analyze the cellular mechanism of nitric oxide (NO) production and its relation to E2, in vitro in brain and peripheral endothelial cells. METHODS Human umbilical endothelial cells (HUVEC) and brain endothelial cells (bEnd.3) were treated with estradiol (E2, 0.1, 10, 100, and 1,000 nM), and supernatant was collected at 0, 5, 15, 30, 60, and 120 min for nitric oxide metabolome (nitrite, NO₂) measurements. Cells were also treated with E2 in the presence of 1400W, a potent eNOS inhibitor, and ICI, an antagonist of estradiol receptors (ERs). Effects of E2 on eNOS protein expression were assessed with Western blot analysis. RESULTS E2 significantly increased NO2 levels irrespective of its concentration in both cell lines by 35 % and 42 % (p < 0.05). The addition of an E2 antagonist, ICI (10 μM), prevented the E2-induced increases in NO2 levels (11 % p > 0.05). The combination of E2 (10 nM) and a NOS inhibitor (1400W, 5 μM) inhibited NO2 increases in addition (4 %, p > 0.05). E2 induced increases in eNOS protein levels and phosphorylated eNOS (eNOS(p)). CONCLUSIONS This study indicates that E2 induces NO level increases in cerebral and peripheral endothelial cells in vitro via eNOS activation and through E2 receptor-mediated mechanisms. Further in vivo studies are warranted to evaluate the therapeutic value of estrogen for the treatment of SAH-induced vasospasm.

Glomerular filtration rate, urine production, and fractional clearance of electrolytes in acute kidney injury in dogs and their association with survival.

BACKGROUND Acute kidney injury (AKI) is common in dogs. Few studies have assessed sequential changes in indices of kidney function in dogs with naturally occurring AKI. OBJECTIVE To document sequential changes of conventional indices of renal function, to better define the course of AKI, and to identify a candidate marker for recovery. ANIMALS Ten dogs with AKI. METHODS Dogs were prospectively enrolled and divided into surviving and nonsurviving dogs. Urine production was measured with a closed system for 7 days. One and 24-hour urinary clearances were performed daily to estimate solute excretion and glomerular filtration rate (GFR). Solute excretion was calculated as an excretion ratio (ER) and fractional clearance (FC) based on both the 1- and 24-hour urine collections. RESULTS Four dogs survived and 6 died. At presentation, GFR was not significantly different between the outcome groups, but significantly (P = .03) increased over time in the surviving, but not in the nonsurviving dogs. Fractional clearance of Na decreased significantly over time (20.2-9.4%, P < .0001) in the surviving, but not in the nonsurviving dogs. The ER and FC of solutes were highly correlated (r, 0.70-0.95). CONCLUSION AND CLINICAL IMPACT Excretion ratio might be used in the clinical setting as a surrogate marker to follow trends in solute excretion. Increased GFR, urine production, and decreased FC of Na were markers of renal recovery. The FC of Na is a simple, noninvasive, and cost-effective method that can be used to evaluate recovery of renal function.

Demographic model of the Swiss cattle population for the years 2009-2011 stratified by gender, age and production type

Demographic composition and dynamics of animal and human populations are important determinants for the transmission dynamics of infectious disease and for the effect of infectious disease or environmental disasters on productivity. In many circumstances, demographic data are not available or of poor quality. Since 1999 Switzerland has been recording cattle movements, births, deaths and slaughter in an animal movement database (AMD). The data present in the AMD offers the opportunity for analysing and understanding the dynamic of the Swiss cattle population. A dynamic population model can serve as a building block for future disease transmission models and help policy makers in developing strategies regarding animal health, animal welfare, livestock management and productivity. The Swiss cattle population was therefore modelled using a system of ordinary differential equations. The model was stratified by production type (dairy or beef), age and gender (male and female calves: 0-1 year, heifers and young bulls: 1-2 years, cows and bulls: older than 2 years). The simulation of the Swiss cattle population reflects the observed pattern accurately. Parameters were optimized on the basis of the goodness-of-fit (using the Powell algorithm). The fitted rates were compared with calculated rates from the AMD and differed only marginally. This gives confidence in the fitted rates of parameters that are not directly deductible from the AMD (e.g. the proportion of calves that are moved from the dairy system to fattening plants).

One Health approach to use of veterinary pharmaceuticals

An estimated 6051 tons of active substances went into the production of veterinary pharmaceuticals (VPs) for the treatment of food animals in the European Union (EU) in 2004, including 5393 tons of antibiotics and 194 tons of antiparasitics (1). With global meat production projected to increase (2) and the growing market for companion animal pharmaceuticals (3), the use of VPs will continue to increase. Although VPs may benefit the health and welfare of domestic animals and the efficiency of food animal production, they can contaminate the environment through manufacturing, treatment of animals, and disposal of carcasses, offal, urine, feces, and unused products (4) (see the chart). This contamination is a threat to nontarget species, including humans. With Spain having recently authorized marketing of a VP that was banned in South Asia in the past decade in light of environmental impacts, we recommend strengthening of current procedures and addition of a more proactive, holistic, One Health approach applicable to all VPs.

The mammary gland in small ruminants: major morphological and functional events underlying milk production – a review

The importance of small ruminants to the dairy industry has increased in recent years, especially in developing countries, where it has a high economic and social impact. Interestingly and despite the fact that the mammary gland is the specialised milk production organ, very few authors studied the modifications occurring in the mammary gland through the lactation period in production animals, particularly in the small ruminants, sheep (Ovis aries) and goat (Capra hircus). Nevertheless, understanding the different mammary gland patterns throughout lactation is essential to improve dairy production. In addition, associating these patterns with different milking frequencies, lactation number or different diets is also of high importance, directly affecting the dairy industry. The mammary gland is commonly composed of parenchyma and stroma, which includes the ductal system, with individual proportions of each changing during the different periods and yields in a lactation cycle. Indeed, during late gestation, as well as during early to mid-lactation, mammary gland expansion occurs, with an increase in the number of epithelial cells and lumen area, which leads to increment of the parenchyma tissue, as well as a reduction of stroma, corresponding macroscopically to the increase in mammary gland volume. Throughout late lactation, the mammary gland volume decreases owing to the regression of the secretory structure. In general, common mammary gland patterns have been shown for both goats and sheep throughout the several lactation stages, although the number of studies is limited. The main objective of this manuscript is to review the colostrogenesis and lactogenesis processes as well as to highlight the mammary gland morphological patterns underlying milk production during the lactation cycle for small ruminants, and to describe potential differences between goats and sheep, hence contributing to a better description of mammary gland development during lactation for these two poorly studied species.

Milk production during the colostral period is not related to the later lactational performance in dairy cows

In dairy cows, milk yield increases rapidly after parturition until a peak at around wk 6 of lactation. However, the description of the shape of the lactation curve is commonly based on weekly average milk yields. For a more detailed analysis of the milk production curve from the very beginning of lactation including the colostral period and the effect of colostrum yield on further lactational performance, the first 10 milkings after parturition, daily milk yields from d 1 to 28 of lactation, and the cumulative milk production on d 100 to 305 of lactation were investigated in 17 primiparous and 39 multiparous cows milked twice daily. Milk yield at the first milking after parturition (colostrum) ranged from 1.3 to 20.7kg (Δ=19.4kg) in multiparous and from 1.8 to 10.9kg in primiparous animals (Δ=9.1kg). At the tenth milking, milk production ranged from 9.2 to 21.5kg (Δ=12.3kg) in multiparous and from 7.0 to 15.2kg (Δ=8.2kg) in primiparous animals. Immediately after parturition, daily milk production increased rapidly, but after approximately 1wk in lactation, the slope of the daily milk production curve flattened and continued more linear. A nonlinear regression equation was used to determine this timely change, which occurred earlier in primiparous (d 6.9±0.3) than in multiparous cows (d 8.2±0.2). The correlation between the amount of first colostrum and milk production during further lactation decreased already from 0.47 on d 5 to 0.32 on d 14. In multiparous cows, the correlation between total milk production of the previous 305d standard lactation and the amount of first colostrum was not significant (correlation=0.29), whereas the correlation with the daily production increased from 0.45 on d 5 to 0.69 on d 14. However, in primiparous animals, correlations between first-colostrum yield and daily milk yields up to d 28 of lactation were not significant, possibly due to the smaller sample size compared with multiparous animals. First-colostrum yield and cumulative milk production of 100, 200, and 305 lactation days were not significantly correlated in multiparous and primiparous cows. In conclusion, the milk production during the first few milkings is widely independent from the overall production level of a cow. Potentially, genetic selection toward lower milk yield during the very first days after parturition at a simultaneously high lactational performance may be a tool to ensure sufficient colostrum quality and to reduce the metabolic load around parturition.

Localization and production of peptide endocannabinoids in the rodent CNS and adrenal medulla.

The endocannabinoid system (ECS) comprises the cannabinoid receptors CB1 and CB2 and their endogenous arachidonic acid-derived agonists 2-arachidonoyl glycerol and anandamide, which play important neuromodulatory roles. Recently, a novel class of negative allosteric CB1 receptor peptide ligands, hemopressin-like peptides derived from alpha hemoglobin, has been described, with yet unknown origin and function in the CNS. Using monoclonal antibodies we now identified the localization of RVD-hemopressin (pepcan-12) and N-terminally extended peptide endocannabinoids (pepcans) in the CNS and determined their neuronal origin. Immunohistochemical analyses in rodents revealed distinctive and specific staining in major groups of noradrenergic neurons, including the locus coeruleus (LC), A1, A5 and A7 neurons, which appear to be major sites of production/release in the CNS. No staining was detected in dopaminergic neurons. Peptidergic axons were seen throughout the brain (notably hippocampus and cerebral cortex) and spinal cord, indicative of anterograde axonal transport of pepcans. Intriguingly, the chromaffin cells in the adrenal medulla were also strongly stained for pepcans. We found specific co-expression of pepcans with galanin, both in the LC and adrenal gland. Using LC-MS/MS, pepcan-12 was only detected in non-perfused brain (∼40 pmol/g), suggesting that in the CNS it is secreted and present in extracellular compartments. In adrenal glands, significantly more pepcan-12 (400-700 pmol/g) was measured in both non-perfused and perfused tissue. Thus, chromaffin cells may be a major production site of pepcan-12 found in blood. These data uncover important areas of peptide endocannabinoid occurrence with exclusive noradrenergic immunohistochemical staining, opening new doors to investigate their potential physiological function in the ECS. This article is part of a Special Issue entitled 'Fluorescent Neuro-Ligands'.

Capital interplays and the self-rated health of young men: results from a cross-sectional study in Switzerland.

INTRODUCTION We apply capital interplay theory to health inequalities in Switzerland by investigating the interconnected effects of parental cultural, economic and social capitals and personal educational stream on the self-rated health of young Swiss men who live with their parents. METHODS We apply logistic regression modelling to self-rated health in original cross-sectional survey data collected during mandatory conscription of Swiss male citizens in 2010 and 2011 (n = 23,975). RESULTS In comparison with sons whose parents completed mandatory schooling only, sons with parents who completed technical college or university were significantly more likely to report very good or excellent self-rated health. Parental economic capital was an important mediating factor in this regard. Number of books in the home (parental cultural capital), family economic circumstances (parental economic capital) and parental ties to influential people (parental social capital) were also independently associated with the self-rated health of the sons. Although sons in the highest educational stream tended to report better health than those in the lowest, we found little evidence for a health-producing intergenerational transmission of capitals via the education stream of the sons. Finally, the positive association between personal education and self-rated health was stronger among sons with relatively poorly educated parents and stronger among sons with parents who were relatively low in social capital. CONCLUSIONS Our study provides empirical support for the role of capital interplays, social processes in which capitals interpenetrate or co-constitute one another, in the intergenerational production of the health of young men in Switzerland.

The effect of extracellular nucleotides on cytokine production and phagocytosis of macrophages

Bacterial sepsis is a severe clinical condition, leading to severe sepsis, septic shock, and death. The complex pathophysiology of sepsis is not yet fully understood. Cytokines, released by immune cells such as macrophages, play an important role in the pathophysiology of sepsis. Kupffer cells are the largest population of macrophages in the body. Purinergic signaling, mediated by different nucleosides and nucleotides, and purinergic receptors, has been shown to have various effects on cytokine release, inflammatory processes and the immune system. In our work with in vitro experiments we studied the effect of extracellular nucleotides on the release of TNFα by primary murine Kupffer cells, and the effect of extracellular nucleotides on the phagocytosis of murine RAW 264.7 and human U-937 cell culture macrophages. Secretion of TNFα was measured using ELISA, phagocytosis of bio particles was measured using a plate reader phagocytosis assay and flow cytometry. Our experiments show, that extracellular LPS stimulate release of TNFα in murine Kupffer cells and that extracellular nucleotides inhibit this effect in a dose dependent matter. Our other experiments show phagocytosis of fluorescence labeled bio particles by both macrophage cell lines RAW 264.7 and U-937 in a dose dependent manner. The experiments could not show an effect of extracellular nucleotides on phagocytosis of cell culture macrophages.