Quantification of bovine leukemia virus proviral DNA using a low-cost real-time polymerase chain reaction

Publication date: Available online 11 April 2018
Source:Journal of Dairy Science
Author(s): M.I. Petersen, I. Alvarez, K.G. Trono, J.P. Jaworski
The detection of bovine leukemia virus (BLV) proviral DNA is an important tool to address whether an animal is infected with BLV. Compared with serological assays, real-time PCR accounts for greater sensitivity and can serve as a confirmatory test for the clarification of inconclusive or discordant serological test results. However, the high cost related to real-time PCR assays has limited their systematic inclusion in BLV surveillance and eradication programs. The aim of the present study was to validate a low-cost quantitative real-time PCR. Interestingly, by using SYBR Green detection dye, we were able to reduce the cost of a single reaction by a factor of 5 compared with most common assays based on the use of fluorogenic probes (i.e., TaqMan technology). This approach allowed a highly sensitive and specific detection and quantification of BLV proviral DNA from purified peripheral blood leukocytes and a milk matrix. Due to its simplicity and low cost, our in-house BLV SYBR quantitative real-time PCR might be used either as a screening or as a confirmatory test in BLV control programs.



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Laboratory evaluation of a novel rapid tube test system for differentiation of mastitis-causing pathogen groups

Publication date: Available online 11 April 2018
Source:Journal of Dairy Science
Author(s): S. Leimbach, V. Krömker
Because clinical mastitis, one of the most common diseases in dairy cows, is routinely treated with antimicrobial substances, it offers a high potential for future reduction of antimicrobial usage. In fact, intramammary antibiotic administration is not advisable in cases of clinical mastitis caused by coliform bacteria, yeasts, or protothecae or in cases with no detectable mastitis pathogen. To avoid unnecessary treatments with antimicrobials for the benefit of animal health and public welfare, the rapid identification of the mastitis-causing pathogens becomes necessary. Therefore, 4 different incubation time schemes for a newly developed tube test system (MastDecide, Quidee GmbH, Homberg, Germany) were analyzed in terms of sensitivity, specificity, negative and positive predictive values, and apparent and true prevalence compared with the conventional microbiological investigation results for 251 clinical mastitis milk samples from 11 dairy farms located in northern Germany. An aliquot (100 µL) of a quarter foremilk sample was taken in both cases. The evaluation of the tube test result after 14 h of incubation at 37°C resulted in sensitivity values of 83.6, 72.2, and 70.7% and specificity values of 94.1, 83.3, and 90.8% for gram-positive cocci, coliform bacteria, and no growth or further pathogens, respectively. Moreover, for the present pathogen distribution, the overall tube test sensitivity was highest after 14 h of incubation (sensitivity = 80.9%; specificity = 70.7%). The described tube test system has the potential to provide a new option for an evidence-based mastitis therapy, with the aim of reducing the future usage of antimicrobials in dairy cows and a larger goal of decreasing antimicrobial resistance. However, a subsequent on-farm test validation should be performed before implementation in an evidence-based mastitis therapy concept can be recommended.



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Effects of feeding milk replacer at 2 rates with pelleted, low-starch or texturized, high-starch starters on calf performance and digestion

Publication date: Available online 11 April 2018
Source:Journal of Dairy Science
Author(s): J.D. Quigley, T.M. Hill, T.S. Dennis, F.X. Suarez-Mena, R.L. Schlotterbeck
Milk replacer (MR) feeding programs have traditionally fed at less than ad libitum amounts to promote calf starter (CS) intake and allow early weaning. More recently, increased amounts of MR preweaning have been shown to increase preweaning ADG, although postweaning growth may be reduced. Several studies suggest that limited postweaning digestion of nutrients in CS may contribute to postweaning growth impairment. It is not clear whether CS formulation might also contribute to differences in postweaning nutrient digestion when calves are fed different MR programs. A 56-d feeding and digestion trial was conducted to compare growth and digestion in 2- to 3-d-old male Holstein calves (n = 48; initially 41.9 kg of body weight) fed a moderate (MRM) or high (MRH) MR program and either a pelleted CS containing 9.9% starch or a texturized CS containing 41.3% starch. Programs were 0.66 kg of dry matter (DM)/d of MR to d 46, then 0.33 kg/d to d 49 (MRM) and 0.85 kg of DM/d to d 5, then 1.07 kg/d to d 42, then 0.53 kg/d to d 49 (MRH). The MR contained 25% crude protein and 18.6% fat and was reconstituted to 13 (MRM) or 15% (MRH) solids. Calves were also assigned randomly to receive a pelleted CS (9.9% starch, 36.9% NDF) or a textured CS (41.3% starch, 13.3% NDF) and water for ad libitum intake for 56 d. During d 31 to 35 and 52 to 56, fecal samples were collected from 5 calves per treatment for estimates of digestibility. Selected nutrients and chromic oxide (d 31–35) or acid-insoluble ash (d 52–56) were analyzed in feed and feces to estimate digestibility. Data were analyzed as a completely randomized design. Repeated measures analysis was performed when data were measured by week. Calves fed MRH gained more body weight (but not hip width) and were more efficient to weaning compared with calves fed MRM, although fecal scores and days treated with medications were greater. We found no effect of CS on animal performance, although calves fed textured CS had higher fecal scores. Digestibilities of nutrients were affected by treatment and time of sampling (5 or 8 wk). At 5 wk, digestion of DM, organic matter, crude protein, and fat were lower and digestion of acid detergent fiber, neutral detergent fiber, and starch were higher in calves fed MRM and reflected greater CS intake. Also, digestion of DM, organic matter, acid detergent fiber, starch, crude protein, and fat were greater in calves fed textured CS at 5 wk. By 8 wk, when CS was the only source of nutrients, digestion of DM, organic matter, acid detergent fiber, and neutral detergent fiber were greater in calves fed MRM and digestion of DM and organic matter were greater, and acid detergent fiber and neutral detergent fiber digestion were lower in calves fed textured CS. Formulation of CS as well as amount of MR offered to young calves influenced animal performance and digestion in this study.



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An evaluation of the effectiveness of a chemical additive based on sodium benzoate, potassium sorbate, and sodium nitrite on the fermentation and aerobic stability of corn silage

Publication date: Available online 11 April 2018
Source:Journal of Dairy Science
Author(s): Limin Kung, Megan L. Smith, Erica Benjamim da Silva, Michelle C. Windle, Thiago C. da Silva, Stephanie A. Polukis
We evaluated the effectiveness of an additive comprising sodium benzoate, potassium sorbate, and sodium nitrite (SSL) as active ingredients for its ability to improve the aerobic stability of corn silages made in North America. In experiment 1, treatment with SSL (1.5 and 2.0 L/t) on whole-plant corn (WPC) was compared with treatment with an additive containing buffered propionic acid and citric acid (BPA; 2 L/t) on corn harvested at 32 and 38% DM and ensiled for 120 d. Silage treated with BPA was higher in ammonia-N and propionic acid relative to other treatments. Treatments with all of the additives had numerically, but not statistically, fewer yeasts compared with untreated silage. Both application rates of SSL resulted in lower concentrations of ethanol compared with untreated and BPA silages. Treatment with BPA improved the aerobic stability of silages compared with untreated silage, but the effect from SSL was markedly greater. In experiment 2, WPC was untreated or treated with 2 or 3 L of SSL/t or a microbial inoculant containing Enterococcus faecium M74, Lactobacillus plantarum CH6072, and Lactobacillus buchneri LN1819 (final total lactic acid bacteria application rate of 150,000 cfu/g of fresh forage). Silages were air stressed for 24 h at 28 and 42 d of storage and ensiled for 49 d before opening. Inoculation had no effect on acid end products, ethanol, number of yeasts, or aerobic stability compared with other treatments. Treatment with SSL decreased the amount of ethanol, had no effect on number of yeasts, and improved aerobic stability in a dose-dependent manner compared with other treatments. In experiment 3, WPC was untreated or treated with 2 L of SSL/t and ensiled for 5, 15, and 30 d. Treatment with SSL resulted in silage with fewer yeasts and lower concentrations of ethanol after all times of ensiling compared with untreated silage. In addition, SSL improved aerobic stability after each period of ensiling, but the effect was more at 15 and 30 d compared with 5 d of storage. Treating WPC with SSL can improve the aerobic stability of corn silage made in North America, and the effect can be observed as soon as 5 d after ensiling.



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Effects of treatment of preweaning dairy calves with recombinant bovine somatotropin on immune responses and somatotropic axis

Publication date: Available online 11 April 2018
Source:Journal of Dairy Science
Author(s): A.L. Belli, R.B. Reis, A. Veronese, R. Moreira, K. Flanagan, J. Driver, C.D. Nelson, J.A. Clapper, M.A. Ballou, K.C. Jeong, R.C. Chebel
Weaning may be associated with negative energy balance and body weight loss when calves are still immunologically immature, predisposing them to infectious diseases. The aim of the present experiment was to investigate the effects of treatment of preweaning dairy calves with recombinant bovine somatotropin (rbST) on the somatotropic axis, selected immune parameters, and hematology of calves around weaning. Thirty-six Holstein female calves were randomly assigned to receive 1.5 to 1.8 mg of rbST (Posilac, Elanco Animal Health, Greenfield, IN) per kilogram of body weight or to receive injections of saline (saline solution 0.9%, Valley Vet Supply, Marysville, KS) every 7 d from 21 to 63 d of life. Calves were fed milk replacer ad libitum from birth to 38 d of age (d −11), when progressive weaning started, and calves were weaned at 49 d of age (d 0). Calves were weighed at birth and weekly from 21 to 63 d of age, when wither height also was measured. Calves were vaccinated with 0.5 mg of ovalbumin on study d −28 and −7. Blood samples were collected on d −28, −25, −21, −11, 0, 3, 7, and 14. Polymorphonuclear leukocytes were isolated and challenged ex vivo with Escherichia coli to determine phagocytosis and oxidative burst capacity. Additionally, expression of cluster of differentiation (CD)62L and CD18 by granulocyte, lymphocyte, and CD14+ monocyte were determined. Blood samples were also used to determine hematological parameters and concentrations of growth hormone, insulin-like growth factor-1, insulin, glucose, fatty acids, β-hydroxybutyrate, haptoglobin, and anti-ovalbumin IgG. Calves treated with rbST had greater concentrations of growth hormone and insulin-like growth factor-1 from d −25 to 14 than control calves, whereas insulin, fatty acid, and β-hydroxybutyrate concentrations did not differ. On d −11, glucose concentration was greater for rbST-treated calves. Treatment did not affect polymorphonuclear lymphocyte phagocytosis and oxidative burst, but intensity of expression of CD62L and CD18 by granulocytes tended to be increased by rbST treatment. Treatment did not affect the concentration of anti-ovalbumin IgG in serum. Haptoglobin concentration was reduced in rbST treated calves on d 3 and we noted a tendency for hematocrit to be lower in rbST-treated calves. Treatment did not affect body weight, wither height, and average daily gain, despite the fact that rbST-treated calves had lower daily milk replacer intake. The relatively minor improvements in immune responses resulting from rbST treatment of weaning calves may not be sufficient to reduce the incidence of infectious diseases.



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Interaction between the physical forms of starter and forage source on growth performance and blood metabolites of Holstein dairy calves

Publication date: Available online 11 April 2018
Source:Journal of Dairy Science
Author(s): H. Omidi-Mirzaei, A. Azarfar, A. Kiani, M. Mirzaei, M.H. Ghaffari
The objective of this study was to investigate the effects of the physical forms of starter and forage sources on feed intake, growth performance, rumen pH, and blood metabolites of dairy calves. Forty male Holstein calves (41.3 ± 3.5 kg of body weight) were used (n = 10 calves per treatment) in a 2 × 2 factorial arrangement of treatments with the factors being physical forms of starter (coarse mash and texturized) and forage source [alfalfa hay (AH) and wheat straw (WS)]. Individually housed calves were randomly assigned to 1 of the 4 dietary treatments, including (1) coarsely mashed (CM; coarse ground grains combined with a mash supplement) starter feed with AH (CM-AH), (2) coarsely mashed starter feed with WS (CM-WS), (3) texturized feed starter (TF; includes steam-flaked corn, steam-rolled barley combined with a pelleted supplement) with AH (TF-AH), and (4) TF with WS (TF-WS). Both starters had the same ingredients and nutrient compositions but differed in their physical forms. Calves were weaned on d 56 and remained in the study until d 70. All calves had free access to drinking water and the starter feeding at all times. No interaction was detected between the physical forms of starter feeds and forage source concerning starter intake, dry matter intake, metabolizable energy (ME) intake, average daily gain (ADG)/ME intake, ADG, and feed efficiency (FE). The preweaning and overall starter feed intake, dry matter intake, and ME intake were greater for calves fed TF starter diets than those fed CM starter diets. The ADG/ME intake was greater for calves fed TF starter diets than that fed CM starter. The FE was greater for calves fed TF starter diets compared with those fed CM starter during the preweaning, postweaning, and overall periods. The WS improved FE during the postweaning period compared with AH. The physical form of starter, forage source, and their interaction did not affect plasma glucose, triglycerides, and very low-density lipoprotein concentrations. Ruminal pH was greater for calves fed TF starter diets than those fed CM starter on d 30 of life. An interaction was observed between the physical forms of starter diets and forage source for β-hydroxybutyrate on d 28. These results showed that when starter diets contained similar ingredients and nutrient contents, processing calf starters to reduce the number of fine particles can improve the growth performance in dairy calves. Furthermore, the provision of WS improved FE and ADG of calves during the postweaning period.



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Selected reaction monitoring mass spectrometry of mastitis milk reveals pathogen-specific regulation of bovine host response proteins

Publication date: Available online 11 April 2018
Source:Journal of Dairy Science
Author(s): Ulrike Kusebauch, Lorenzo E. Hernández-Castellano, Stine L. Bislev, Robert L. Moritz, Christine M. Røntved, Emøke Bendixen
Mastitis is a major challenge to bovine health. The detection of sensitive markers for mastitis in dairy herds is of great demand. Suitable biomarkers should be measurable in milk and should report pathogen-specific changes at an early stage to support earlier diagnosis and more efficient treatment. However, the identification of sensitive biomarkers in milk has remained a challenge, in part due to their relatively low concentration in milk. In the present study, we used a selected reaction monitoring (SRM) mass spectrometry approach, which allowed the absolute quantitation of 13 host response proteins in milk for the first time. These proteins were measured over a 54-h period upon an in vivo challenge with cell wall components from either gram-negative (lipopolysaccharide from Escherichia coli; LPS) or gram-positive bacteria (peptidoglycan from Staphylococcus aureus; PGN). Whereas our data clearly demonstrate that all challenged animals have consistent upregulation of innate immune response proteins after both LPS and PGN challenge, the data also reveal clearly that LPS challenge unleashes faster and shows a more intense host response compared with PGN challenge. Biomarker candidates that may distinguish between gram-negative and gram-positive bacteria include α-2 macroglobulin, α-1 antitrypsin, haptoglobin, serum amyloid A3, cluster of differentiation 14, calgranulin B, cathepsin C, vanin-1, galectin 1, galectin 3, and IL-8. Our approach can support further studies of large cohorts of animals with natural occurring mastitis, to validate the relevance of these suggested biomarkers in dairy production.



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Feeding reduced-fat dried distillers grains with solubles to lactating Holstein dairy cows does not alter milk composition or cause late blowing in cheese

Publication date: Available online 11 April 2018
Source:Journal of Dairy Science
Author(s): E.D. Testroet, D.C. Beitz, M.R. O'Neil, A.L. Mueller, H.A. Ramirez-Ramirez, S. Clark
Feeding dried distillers grains with solubles (DDGS) to lactating dairy cows has been implicated as a cause of late blowing defects in the production of Swiss-style cheeses. Our objectives were (1) to test the effect of feeding reduced-fat DDGS (RF-DDGS; ∼6% fat) to lactating dairy cows on the composition of milk and on the suitability of the milk for production of baby Swiss cheese and (2) to evaluate the effect of diet on cow lactation performance. Lactating Holstein dairy cows were fed both dietary treatments in a 2 × 2 crossover design. Cows were housed in a 48-cow freestall pen equipped with individual feeding gates to record feed intake. The control diet was a corn, corn silage, and alfalfa hay diet supplemented with mechanically expelled soybean meal. The experimental diet was the same base ration, but 20% (dry matter basis) RF-DDGS were included in place of the expelled soybean meal. The RF-DDGS diet was additionally supplemented with rumen-protected lysine; diets were formulated to be isoenergetic and isonitrogenous. Cows were allowed ad libitum access to feed and water, fed twice daily, and milked 3 times daily. For cheese production, milk was collected and pooled 6 times for each dietary treatment. There was no treatment effect on milk yield (35.66 and 35.39 kg/d), milk fat production (1.27 and 1.25 kg/d), milk fat percentage (3.65 and 3.61%), milk protein production (1.05 and 1.08 kg/d), lactose percentage (4.62 and 4.64%), milk total solids (12.19 and 12.28%), and somatic cell count (232.57 and 287.22 × 10³ cells/mL) for control and RF-DDGS, respectively. However, dry matter intake was increased by treatment, which implied a reduction in feed efficiency. Milk protein percentage also increased (3.01 and 3.11%), whereas milk urea nitrogen decreased (14.18 and 12.99 mg/dL), indicating that protein utilization may be more efficient when cows are fed RF-DDGS. No differences in cheese were observed by a trained panel except cheese appearance; control cheese eyes were significantly, but not practically, larger than the RF-DDGS cheese. These results indicate that RF-DDGS can be effectively used in the rations of lactating Holstein cows with no deleterious effects on milk production and composition and metrics of the physiology of the cow (i.e., blood glucose and nonesterified fatty acids); however, feeding RF-DDGS increased dry matter intake, which decreased feed efficiency. Finally, feeding RF-DDGS did not negatively influence quality and suitability of milk for production of baby Swiss cheese.



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In vitro bioassessment of the immunomodulatory activity of Saccharomyces cerevisiae components using bovine macrophages and Mycobacterium avium ssp. paratuberculosis

Publication date: Available online 11 April 2018
Source:Journal of Dairy Science
Author(s): Z. Li, H. Kang, Q. You, F. Ossa, P. Mead, M. Quinton, N.A. Karrow
The yeast Saccharomyces cerevisiae and its components are used for the prevention and treatment of enteric disease in different species; therefore, they may also be useful for preventing Johne's disease, a chronic inflammatory bowel disease of ruminants caused by Mycobacterium avium ssp. paratuberculosis (MAP). The objective of this study was to identify potential immunomodulatory S. cerevisiae components using a bovine macrophage cell line (BOMAC). The BOMAC phagocytic activity, reactive oxygen species production, and immune-related gene (IL6, IL10, IL12p40, IL13, IL23), transforming growth factor β, ARG1, CASP1, and inducible nitric oxide synthase expression were investigated when BOMAC were cocultured with cell wall components from 4 different strains (A, B, C, and D) and 2 forms of dead yeast from strain A. The BOMAC phagocytosis of mCherry-labeled MAP was concentration-dependently attenuated when BOMAC were cocultured with yeast components for 6 h. Each yeast derivative also induced a concentration-dependent increase in BOMAC reactive oxygen species production after a 6-h exposure. In addition, BOMAC mRNA expression of the immune-related genes was investigated after 6 and 24 h of exposure to yeast components. All yeast components were found to regulate the immunomodulatory genes of BOMAC; however, the response varied among components and over time. The in vitro bioassessment studies reported here suggest that dead yeast and its cell wall components may be useful for modulating macrophage function before or during MAP infection.



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Associations between bone and energy metabolism in cows fed diets differing in level of dietary cation-anion difference and supplemented with cholecalciferol or calcidiol

Publication date: Available online 11 April 2018
Source:Journal of Dairy Science
Author(s): R.M. Rodney, N.P. Martinez, P. Celi, E. Block, P.C. Thomson, G. Wijffels, D.R. Fraser, J.E.P. Santos, I.J. Lean
Bone-derived hormones play an important role in metabolism. This study examined the hypothesis that interactions between bone and energy metabolism, particularly those involving osteocalcin, are present in dairy cattle and have feedback mechanisms over time. Associations between metabolites in blood were examined in 32 Holstein cows blocked by parity and milk yield and randomly allocated to diets containing either 0.27 mg/kg dry matter (DM) calcidiol or cholecalciferol for an anticipated intake of 3 mg/d (120,000 IU/d) at 11 kg of DM, and positive (+130 mEq/kg DM) or negative (−130 mEq/kg DM) dietary cation-anion difference (DCAD) from 252 d of gestation to calving. Blood was sampled every 3 d, from 9 d prepartum to 30 d postpartum, and plasma concentrations of vitamin D3, 25-hydroxyvitamin D3, adiponectin, C-telopeptide of type 1 collagen (CTX1), glucose, insulin-like growth factor 1 (IGF1), insulin, undercarboxylated osteocalcin (uOC), and carboxylated osteocalcin (cOC) were determined. Feeding calcidiol compared with cholecalciferol increased plasma concentrations of 25-hydroxyvitamin D3 pre- (264.2 ± 8.0 vs. 61.3 ± 8.0 ng/mL) and postpartum (170.8 ± 6.2 vs. 51.3 ± 6.2 ng/mL) but decreased concentrations of vitamin D3 pre- (1.2 ± 0.6 vs. 14.5 ± 0.6 ng/mL) and postpartum (1.9 ± 0.4 vs. 3.2 ± 0.6 ng/mL). Prepartum, cows fed the negative DCAD diet had reduced concentrations of vitamin D3 and glucose compared with cows fed a positive DCAD. The combination of negative DCAD and cholecalciferol reduced IGF1 concentrations prepartum. The DCAD treatment had no effect on postpartum concentrations of metabolites. Nulliparous cows had increased concentrations of OC, CTX1, IGF1, glucose, and insulin compared with parous cows. Time series analysis identified associations between metabolites on the same day and over 3-d lags up to ±9 d that suggest feedback between 25-hydroxyvitamin D3 and vitamin D3 in the negative lags, indicating that 25-hydroxyvitamin D3 may exert feedback on vitamin D3 but not vice versa. We found evidence of a feedback mechanism between vitamin D3 and IGF1, with positive effect size (ES) on the same day and 3 d later, and negative ES 9 d later, that was more evident in cholecalciferol-fed cows. This suggests an important role of IGF1 in integrating bone metabolism with energy and protein metabolic pathways. Evidence of feedback was found between uOC and particularly cOC with IGF1, with positive ES on the same day but negative ES 6 d before and 6 d after. An association between uOC or cOC and IGF1 has not been previously identified in cattle and suggests that both uOC and cOC may have marked biological activity. Associations between OC and insulin identified in mice were not observed herein, although associations between OC and glucose were similar to those between IGF1 and glucose, supporting associations between glucose, OC, and IGF1. We provide further statistical evidence of crosstalk between vitamin D compounds, bone hormones, and energy metabolism in cattle. In particular, associations between uOC or cOC and IGF1 may provide links between prepartum diets and observations of prolonged increases in milk production and allow better control of peripartum metabolism.



https://ift.tt/2HuGAyN

Solution-liquid-solid growth of CuInTe2 nanowires as lithium-ion battery anodes

Publication date: 5 July 2018
Source:Materials & Design, Volume 149
Author(s): Shao-Lou Jheng, Jee-yee Chen, Hsing-Yu Tuan
For the first time, CuInTe2 nanowires in I–III–VI2 chalcopyrite ternary system were synthesized via the bismuth (Bi)-seeded solution-liquid-solid (SLS) growth under 350°C. CuInTe2 nanowires were made by using the mixture of Cu(acac)2, InCl3 and Te powder as precursors, bismuth 2-ethylhexanoate [Bi[N(SiMe3)2]3] as growth seed solution and tri-n-octylphosphine (TOP) as solvents, respectively. As-made CuInTe2 nanowires are single crystals with a tetragonal chalcopyrite structure with diameters ranging from 10 to 200nm. In addition, as an anode material in the lithium ion batteries, the capacity of CuInTe2 nanowires in charging/discharging rate of 0.1C capacity of 780mAh/g after 200cycles (1C=572mAh/g), showing the accomplished reversibility. Furthermore, the discharge capacity (385mAh/g) at 5C rate is still higher than the theoretical capacity of graphite (372mAh/g), showing the attractive performance in the fast charging/discharging rates.

Graphical abstract

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Finite element modelling and characterization of 3D cellular microstructures for the design of a cementless biomimetic porous hip stem

Publication date: 5 July 2018
Source:Materials & Design, Volume 149
Author(s): Hassan Mehboob, Faris Tarlochan, Ali Mehboob, Seung-Hwan Chang
Titanium porous cellular microstructures are commonly used in bone mimetic implants. The orientations of the internal strut architectures of these microstructures affect the mechanical performance under various loads; however, poor architectural designs may result in their failure. Three-dimensional (3D) finite element models of cubic, diamond, and body-centered cubic (BCC) geometries were constructed with 1–4 numbers of unit cells and 4–10-mm unit cell size. Mechanical testing of the finite models of the cubic, diamond, and BCC structures with porosities of 20–90% was performed under compression, bending, and torsional loads. The BCC structure showed moderate and relatively isotropic mechanical properties compared with those of the diamond and cubic structures. A design space for a BCC porous structure with a porosity of 40–65% was estimated to model a complete porous stem to mimic the bone properties. Furthermore, the stems with the determined porous mechanical properties of the BCC microstructures with 20–90% porosities were tested under physiological loading conditions. It was found that a porosity of 47.3% of the BCC structure exhibits the closest stiffness (469N/mm) to an intact bone (422N/mm). This was predicted by our suggested design space of the porosity.

Graphical abstract

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Stressful Events as Teaching Signals for the Brain

Publication date: Available online 11 April 2018
Source:Trends in Cognitive Sciences
Author(s): Sabrina Trapp, John P. O'Doherty, Lars Schwabe
Stressful events are better remembered than mundane events. We explain this advantage by reconceptualizing stress in terms of cumulative prediction errors (PEs) that promote rapid learning of events. This proposal integrates the effects of stress on perception and memory, and provides exciting new perspectives for research on stress and cognition.



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Correction to: Ultrasound enhanced activation of peroxydisulfate by activated carbon fiber for decolorization of azo dye

Abstract

The correct name of the 5th Author is Jiabin Chen.

https://ift.tt/2ILNyP5

Pituitary Adenylate Cyclase-Activating Polypeptide is a Potent Broad-Spectrum Antimicrobial Peptide: Structure-Activity Relationships

Publication date: Available online 11 April 2018
Source:Peptides
Author(s): Charles G. Starr, Jerome L. Maderdrut, Jing He, David H. Coy, William C. Wimley
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a naturally occurring cationic peptide with potent immunosuppressant and cytoprotective activities. We now show that full length PACAP38 and to a lesser extent, the truncated form PACAP27, and the closely related vasoactive intestinal peptide (VIP) and secretin had antimicrobial activity against the Gram-negative bacteria Escherichia coli in the radial diffusion assay. PACAP38 was more potent than either the bovine neutrophil antimicrobial peptide indolicidin or the synthetic antimicrobial peptide ARVA against E. coli. PACAP38 also had activity against the Gram-positive bacteria Staphylococcus aureus in the same assay with comparable potency to indolicidin and ARVA. In the more stringent broth dilution assay, PACAP38 had moderate sterilizing activity against E. coli, and potent sterilizing activity against the Gram-negative bacteria Pseudomonas aeruginosa. PACAP27, VIP and secretin were much less active than PACAP38 in this assay. PACAP38 also had some activity against the Gram-positive bacteria Bacillus cereus in the broth dilution assay. Many exopeptidase-resistant analogs of PACAP38, including both receptor agonists and antagonists, had antimicrobial activities equal to, or better than PACAP38, in both assays. PACAP38 made the membranes of E. coli permeable to SYTOX Green, suggesting a classical membrane lytic mechanism. These data suggest that analogs of PACPAP38 with a wide range of useful biological activities can be made by judicious substitutions in the sequence.



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Small Cell Neuroendocrine Carcinoma: A Rare Nasopharyngeal Malignancy with Aggressive Clinical Course

Abstract

Primary small cell neuroendocrine carcinoma is uncommon in head and neck region, with occasional cases in nasopharynx. Distinction from other round cell tumors is imperative to ensure optimal patient management. We present a case of a 30-year-old woman who presented with a rapidly growing nasopharyngeal mass.

https://ift.tt/2GTJmwd

Microwear textures of Australopithecus africanus and Paranthropus robustus molars in relation to paleoenvironment and diet

Publication date: June 2018
Source:Journal of Human Evolution, Volume 119
Author(s): Alexandria Peterson, Elicia F. Abella, Frederick E. Grine, Mark F. Teaford, Peter S. Ungar
The importance of diet in primate ecology has motivated the use of a variety of methods to reconstruct dietary habits of extinct hominin taxa. Dental microwear is one such approach that preserves evidence from consumed food items. This study is based on 44 specimens of Australopithecus africanus from Makapansgat and Sterkfontein, and 66 specimens of Paranthropus robustus from Swartkrans, Kromdraai and Drimolen. These samples enable examination of potential differences between the two assemblages of A. africanus, and among the various assemblages of P. robustus in relation to the paleoenvironmental reconstructions that have been proffered for each fossil site. Sixteen microwear texture variables were recorded for each specimen from digital elevation models generated using a white-light confocal profiler. Only two of these differ significantly between the Makapansgat and Sterkfontein samples of A. africanus. None of the microwear texture variables differs significantly among the samples of P. robustus. On the other hand, P. robustus has significantly higher values than A. africanus for 11 variables related to feature complexity, size, and depth; P. robustus exhibits rougher surfaces that comprise larger, deeper features. In contrast, A. africanus has smoother, simpler wear surfaces with smaller, shallower and more anisotropic features. As for possible habitat differences among the various sites, only a relatively small number of subtle differences are evident between the specimens of A. africanus from Makapansgat and Sterkfontein, and there are none among the specimens of P. robustus from various deposits. As such, it is reasonable to conclude that, while subtle differences in microwear textures may reflect differences in background habitats, the wear fabric differences between P. robustus and A. africanus are most reasonably interpreted as having been driven by dietary differences.



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Using modern human cortical bone distribution to test the systemic robusticity hypothesis

Publication date: June 2018
Source:Journal of Human Evolution, Volume 119
Author(s): Karen L. Baab, Lynn E. Copes, Devin L. Ward, Nora Wells, Frederick E. Grine
The systemic robusticity hypothesis links the thickness of cortical bone in both the cranium and limb bones. This hypothesis posits that thick cortical bone is in part a systemic response to circulating hormones, such as growth hormone and thyroid hormone, possibly related to physical activity or cold climates. Although this hypothesis has gained popular traction, only rarely has robusticity of the cranium and postcranial skeleton been considered jointly. We acquired computed tomographic scans from associated crania, femora and humeri from single individuals representing 11 populations in Africa and North America (n = 228). Cortical thickness in the parietal, frontal and occipital bones and cortical bone area in limb bone diaphyses were analyzed using correlation, multiple regression and general linear models to test the hypothesis. Absolute thickness values from the crania were not correlated with cortical bone area of the femur or humerus, which is at odds with the systemic robusticity hypothesis. However, measures of cortical bone scaled by total vault thickness and limb cross-sectional area were positively correlated between the cranium and postcranium. When accounting for a range of potential confounding variables, including sex, age and body mass, variation in relative postcranial cortical bone area explained ∼20% of variation in the proportion of cortical cranial bone thickness. While these findings provide limited support for the systemic robusticity hypothesis, cranial cortical thickness did not track climate or physical activity across populations. Thus, some of the variation in cranial cortical bone thickness in modern humans is attributable to systemic effects, but the driving force behind this effect remains obscure. Moreover, neither absolute nor proportional measures of cranial cortical bone thickness are positively correlated with total cranial bone thickness, complicating the extrapolation of these findings to extinct species where only cranial vault thickness has been measured.



https://ift.tt/2GRoVjC

Obesity induced T cell dysfunction and implications for cancer immunotherapy

Publication date: April 2018
Source:Current Opinion in Immunology, Volume 51
Author(s): Ethan G Aguilar, William J Murphy
Obesity has been shown to increase risk for a number of different disorders, including cancer. In addition, obesity is also associated with immune dysfunction, which could contribute to its strong association with other comorbidities. Recently, the immune system has been found to be heavily regulated by changes in metabolism. In particular, T cells are able to respond to intrinsic metabolic regulatory mechanisms, as well as extrinsic factors such as the changes in metabolite availability. The dysfunctional metabolic environment created by obesity could therefore have a direct impact on T cell responses. In this review, we highlight recent findings in the fields of T cell biology and obesity, with a focus on mechanisms driving T cell dysfunction and potential implications for immunotherapeutic treatment of cancer.



https://ift.tt/2v6PfF4

Mass cytometry: a powerful tool for dissecting the immune landscape

Publication date: April 2018
Source:Current Opinion in Immunology, Volume 51
Author(s): Yannick Simoni, Melissa Hui Yen Chng, Shamin Li, Michael Fehlings, Evan W Newell
Advancement in methodologies for single cell analysis has historically been a major driver of progress in immunology. Currently, high dimensional flow cytometry, mass cytometry and various forms of single cell sequencing-based analysis methods are being widely adopted to expose the staggering heterogeneity of immune cells in many contexts. Here, we focus on mass cytometry, a form of flow cytometry that allows for simultaneous interrogation of more than 40 different marker molecules, including cytokines and transcription factors, without the need for spectral compensation. We argue that mass cytometry occupies an important niche within the landscape of single-cell analysis platforms that enables the efficient and in-depth study of diverse immune cell subsets with an ability to zoom-in on myeloid and lymphoid compartments in various tissues in health and disease. We further discuss the unique features of mass cytometry that are favorable for combining multiplex peptide-MHC multimer technology and phenotypic characterization of antigen specific T cells. By referring to recent studies revealing the complexities of tumor immune infiltrates, we highlight the particular importance of this technology for studying cancer in the context of cancer immunotherapy. Finally, we provide thoughts on current technical limitations and how we imagine these being overcome.



https://ift.tt/2qpJm0Z

Global gridded anthropogenic emissions inventory of carbonyl sulfide

Publication date: June 2018
Source:Atmospheric Environment, Volume 183
Author(s): Andrew Zumkehr, Tim W. Hilton, Mary Whelan, Steve Smith, Le Kuai, John Worden, J. Elliott Campbell
Atmospheric carbonyl sulfide (COS or OCS) is the most abundant sulfur containing gas in the troposphere and is an atmospheric tracer for the carbon cycle. Gridded inventories of global anthropogenic COS are used for interpreting global COS measurements. However, previous gridded anthropogenic data are a climatological estimate based on input data that is over three decades old and are not representative of current conditions. Here we develop a new gridded data set of global anthropogenic COS sources that includes more source sectors than previously available and uses the most current emissions factors and industry activity data as input. Additionally, the inventory is provided as annually varying estimates from years 1980–2012 and employs a source specific spatial scaling procedure. We estimate a global source in year 2012 of 406 Gg S y⁻¹ (range of 223–586 Gg S y⁻¹), which is highly concentrated in China and is twice as large as the previous gridded inventory. Our large upward revision in the bottom-up estimate of the source is consistent with a recent top-down estimate based on air-monitoring and Antarctic firn data. Furthermore, our inventory time trends, including a decline in the 1990's and growth after the year 2000, are qualitatively consistent with trends in atmospheric data. Finally, similarities between the spatial distribution in this inventory and remote sensing data suggest that the anthropogenic source could potentially play a role in explaining a missing source in the global COS budget.



https://ift.tt/2HuKckg

Corrigendum.

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Corrigendum.

Oncoimmunology. 2018;7(4):e1431073

Authors:

Abstract
[This corrects the article DOI: 10.1080/2162402X.2017.1408750.].

PMID: 29634049 [PubMed - in process]

https://ift.tt/2INUX0t

A blood dendritic cell vaccine for acute myeloid leukemia expands anti-tumor T cell responses at remission.

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A blood dendritic cell vaccine for acute myeloid leukemia expands anti-tumor T cell responses at remission.

Oncoimmunology. 2018;7(4):e1419114

Authors: Hsu JL, Bryant CE, Papadimitrious MS, Kong B, Gasiorowski RE, Orellana D, McGuire HM, Groth BFS, Joshua DE, Ho PJ, Larsen S, Iland HJ, Gibson J, Clark GJ, Fromm PD, Hart DN

Abstract
Only modest advances in AML therapy have occurred in the past decade and relapse due to residual disease remains the major challenge. The potential of the immune system to address this is evident in the success of allogeneic transplantation, however this leads to considerable morbidity. Dendritic cell (DC) vaccination can generate leukemia-specific autologous immunity with little toxicity. Promising results have been achieved with vaccines developed in vitro from purified monocytes (Mo-DC). We now demonstrate that blood DC (BDC) have superior function to Mo-DC. Whilst BDC are reduced at diagnosis in AML, they recover following chemotherapy and allogeneic transplantation, can be purified using CMRF-56 antibody technology, and can stimulate functional T cell responses. While most AML patients in remission had a relatively normal T cell landscape, those who had received fludarabine as salvage therapy have persistent T cell abnormalities including reduced number, altered subset distribution, failure to expand, and increased activation-induced cell death. Furthermore, PD-1 and TIM-3 are increased on CD4T cells in AML patients in remission and their blockade enhances the expansion of leukemia-specific T cells. This confirms the feasibility of a BDC vaccine to consolidate remission in AML and suggests it should be tested in conjunction with checkpoint blockade.

PMID: 29632738 [PubMed]

https://ift.tt/2Hfzq3q

Anti-Melanoma immunity and local regression of cutaneous metastases in melanoma patients treated with monobenzone and imiquimod; a phase 2 a trial.

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Anti-Melanoma immunity and local regression of cutaneous metastases in melanoma patients treated with monobenzone and imiquimod; a phase 2 a trial.

Oncoimmunology. 2018;7(4):e1419113

Authors: Teulings HE, Tjin EPM, Willemsen KJ, van der Kleij S, Ter Meulen S, Kemp EH, Krebbers G, van Noesel CJM, Franken CLMC, Drijfhout JW, Melief CJM, Nieuweboer-Krobotova L, Nieweg OE, van der Hage JA, van der Veen JPW, Relyveld GN, Luiten RM

Abstract
Vitiligo development in melanoma patients during immunotherapy is a favorable prognostic sign and indicates breakage of tolerance against melanocytic/melanoma antigens. We investigated a novel immunotherapeutic approach of the skin-depigmenting compound monobenzone synergizing with imiquimod in inducing antimelanoma immunity and melanoma regression. Stage III-IV melanoma patients with non-resectable cutaneous melanoma metastases were treated with monobenzone and imiquimod (MI) therapy applied locally to cutaneous metastases and adjacent skin during 12 weeks, or longer. Twenty-one of 25 enrolled patients were evaluable for clinical assessment at 12 weeks. MI therapy was well-tolerated. Partial regression of cutaneous metastases was observed in 8 patients and stable disease in 1 patient, reaching the statistical endpoint of treatment efficacy. Continued treatment induced clinical response in 11 patients, including complete responses in three patients. Seven patients developed vitiligo-like depigmentation on areas of skin that were not treated with MI therapy, indicating a systemic effect of MI therapy. Melanoma-specific antibody responses were induced in 7 of 17 patients tested and melanoma-specific CD8+T-cell responses in 11 of 15 patients tested. These systemic immune responses were significantly increased during therapy as compared to baseline in responding patients. This study shows that MI therapy induces local and systemic anti-melanoma immunity and local regression of cutaneous metastases in 38% of patients, or 52% during prolonged therapy. This study provides proof-of-concept of MI therapy, a low-cost, broadly applicable and well-tolerated treatment for cutaneous melanoma metastases, attractive for further clinical investigation.

PMID: 29632737 [PubMed]

https://ift.tt/2EDUzPJ

Safety and activity of PD-1 blockade-activated DC-CIK cells in patients with advanced solid tumors.

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Safety and activity of PD-1 blockade-activated DC-CIK cells in patients with advanced solid tumors.

Oncoimmunology. 2018;7(4):e1417721

Authors: Chen CL, Pan QZ, Weng DS, Xie CM, Zhao JJ, Chen MS, Peng RQ, Li DD, Wang Y, Tang Y, Wang QJ, Zhang ZL, Zhang XF, Jiang LJ, Zhou ZQ, Zhu Q, He J, Liu Y, Zhou FJ, Xia JC

Abstract
Cytokine-induced killer (CIK) cells that are stimulated using mature dendritic cells (DCs), referred to as (DC-CIK cells) exhibit superior anti-tumor potency. Anti-programmed death-1 (PD-1) antibodies reinvigorate T cell-mediated antitumor immunity. This phase I study aimed to assess the safety and clinical activity of immunotherapy with PD-1 blockade (pembrolizumab)-activated autologous DC-CIK cells in patients with advanced solid tumors. Patients with selected types of advanced solid tumors received a single intravenous infusion of activated autologous DC-CIK cells weekly for the first month and every 2 weeks thereafter. The primary end points were safety and adverse event (AE) profiles. Antitumor responses, overall survival (OS), progression-free survival (PFS) and cytolytic activity were secondary end points. Treatment-related AEs occurred in 20/31 patients. Grade 3 or 4 toxicities, including fever and chills, were observed in two patients. All treatment-related AEs were reversible or controllable. The cytotoxicity of DC-CIK cells induced up-regulation of PD-L1 expression on autologous tumor cells. When activated using pembrolizumab ex vivo, DC-CIK cells exerted superior antitumor properties and elevated IFN-γ secretion. Objective responses (complete or partial responses) were observed in 7 of the 31patients.These responses were durable, with 6 of 7 responses lasting more than 5 months. The overall disease control rate in the patients was 64.5%. At the time of this report, the median OS and PFS were 270 and 162 days, respectively. In conclusions, treatment with pembrolizumab-activated autologous DC-CIK cells was safe and exerted encouraging antitumor activity in advanced solid tumors. A larger phase II trial is warranted.

PMID: 29632736 [PubMed]

https://ift.tt/2qpLdTc

Bladder cancer-associated cancer-testis antigen-derived long peptides encompassing both CTL and promiscuous HLA class II-restricted Th cell epitopes induced CD4+ T cells expressing converged T-cell receptor genes in vitro.

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Bladder cancer-associated cancer-testis antigen-derived long peptides encompassing both CTL and promiscuous HLA class II-restricted Th cell epitopes induced CD4+ T cells expressing converged T-cell receptor genes in vitro.

Oncoimmunology. 2018;7(4):e1415687

Authors: Tsuruta M, Ueda S, Yew PY, Fukuda I, Yoshimura S, Kishi H, Hamana H, Hirayama M, Yatsuda J, Irie A, Senju S, Yuba E, Kamba T, Eto M, Nakayama H, Nishimura Y

Abstract
DEP domain containing 1 (DEPDC1) and M-phase phosphoprotein 1 (MPHOSPH1) are human cancer testis antigens that are frequently overexpressed in urinary bladder cancer. In a phase I/II clinical trial, a DEPDC1- and MPHOSPH1-derived short peptide vaccine demonstrated promising efficacy in preventing bladder cancer recurrence. Here, we aimed to identify long peptides (LPs) derived from DEPDC1 and MPHOSPH1 that induced both T-helper (Th) cells and tumor-reactive cytotoxic T lymphocytes (CTLs). Stimulation of peripheral blood mononuclear cells (PBMCs) from healthy donors with the synthetic DEPDC1- and MPHOSPH1-LPs predicted to bind to promiscuous human leukocyte antigen (HLA) class II molecules by a computer algorithm induced specific CD4+ T cells as revealed by interferon-γ enzyme-linked immunospot assays. Three of six LPs encompassed HLA-A2- or -A24-restricted CTL epitopes or both, and all six LPs stimulated DEPDC1- or MPHOSPH1-specific Th cells restricted by promiscuous and frequently observed HLA class II molecules in the Japanese population. Some LPs are naturally processed from the proteins in DCs, and the capacity of these LPs to cross-prime CTLs was confirmed in vivo using HLA-A2 or -A24 transgenic mice. The LP-specific and HLA class II-restricted T-cell responses were also observed in PBMCs from patients with bladder cancer. Repeated stimulation of PBMCs with DEPDC1-LPs and MPHOSPH1-LPs yielded clonal Th cells expressing specific T-cell receptor (TCR)-α and β genes. These DEPDC1- or MPHOSPH1-derived LPs may have applications in immunotherapy in patients with bladder cancer, and the TCR genes identified may be useful for monitoring of Th cells specific to LPs in vivo.

PMID: 29632734 [PubMed]

https://ift.tt/2ILsHLN

A novel MDSC-induced PD-1-PD-L1+ B-cell subset in breast tumor microenvironment possesses immuno-suppressive properties.

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A novel MDSC-induced PD-1-PD-L1+ B-cell subset in breast tumor microenvironment possesses immuno-suppressive properties.

Oncoimmunology. 2018;7(4):e1413520

Authors: Shen M, Wang J, Yu W, Zhang C, Liu M, Wang K, Yang L, Wei F, Wang SE, Sun Q, Ren X

Abstract
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of myeloid cells that suppress T-cell activity in a tumor microenvironment. However, the suppressive function of MDSCs on B cells and its underlying mechanism remain unclear. Here, we show that in 4T1 breast cancer mice, a significantly increased number of MDSCs, in parallel with splenic B cells, are accumulated when compared to normal mice. In the presence of MDSCs, the surface molecules of B cells are remolded, with checkpoint-related molecules such as PD-1 and PD-L1 changing prominently. MDSCs also emerge as vital regulators in B-cell immune functions such as proliferation, apoptosis and the abilities to secrete antibodies and cytokines. Our study further identifies that MDSCs can transform normal B cells to a subtype of immuno- regulatory B cells (Bregs) which inhibit T-cell response. Furthermore, we identified a novel kind of Bregs with a specific phenotype PD-1-PD-L1+CD19+, which exert the greatest suppressive effects on T cells in comparison with the previously reported Bregs characterized as CD1d+CD5+CD19+, CD5+CD19+ and Interleukin (IL)-10-secreting B cells. Our results highlight that MDSCs regulate B-cell response and may serve as a therapeutic approach in anti-tumor treatment. Investigation of this new Breg subtype extends our understanding of regulation of T-cell response and sheds new light on anti-tumor immunity and immune therapy.

PMID: 29632731 [PubMed]

https://ift.tt/2qpLaH0

Evaluation of programmed cell death protein 1 (PD-1) expression as a prognostic biomarker in patients with clear cell renal cell carcinoma.

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Evaluation of programmed cell death protein 1 (PD-1) expression as a prognostic biomarker in patients with clear cell renal cell carcinoma.

Oncoimmunology. 2018;7(4):e1413519

Authors: Kim KS, Sekar RR, Patil D, Dimarco MA, Kissick HT, Bilen MA, Osunkoya AO, Master VA

Abstract
Programmed cell death protein 1 (PD-1) immune checkpoint inhibitors have shown activity in patients with advanced renal cell carcinoma (RCC). However, the role of PD-1 expression in tumor-infiltrating lymphocytes (TILs) as a biomarker for poor outcome is not clear. In this study, we evaluated the prognostic value of TIL PD-1 expression in patients with clear cell RCC (ccRCC). 82 patients who underwent nephrectomy for localized or metastatic ccRCC and followed up for at least four years were searched from our database and retrospectively enrolled. Their fixed primary tumor specimens were stained with anti-PD-1 (NAT105). The specimens were classified as negative or positive for PD-1 expression, and the positive specimens were further scored in 10% increments. 37 (45.12%) patients were negative (<1% stained), 26 (31.71%) patients were low (<10 and 10%), and 19 (23.17%) patients were high (20-50%) for PD-1 expression. The prognostic value of TIL PD-1 expression was evaluated by univariate Cox proportional hazards regression on overall and recurrence-free survivals. Higher TIL PD-1 expression was not associated with increased risk of death (P = 0.336) or with increased risk of recurrence (P = 0.572). Higher primary tumor stage was associated with increased risk of recurrence (P = 0.003), and higher Fuhrman nuclear grade was associated with increased risk of death (P <0.001) and with increased risk of recurrence (P <0.001). Our study shows that TIL PD-1 expression by immunohistochemistry (IHC) does not correlate with poor clinical outcome in patients with ccRCC and is inferior to established prognosticating tools.

PMID: 29632730 [PubMed]

https://ift.tt/2IIzkyz

Repolarizing heterogeneous leukemia-associated macrophages with more M1 characteristics eliminates their pro-leukemic effects.

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Repolarizing heterogeneous leukemia-associated macrophages with more M1 characteristics eliminates their pro-leukemic effects.

Oncoimmunology. 2018;7(4):e1412910

Authors: Yang X, Feng W, Wang R, Yang F, Wang L, Chen S, Ru Y, Cheng T, Zheng G

Abstract
Macrophages exhibit phenotypic heterogeneity under both physiological and pathological conditions. Applications targeting M2-like tumor-associated macrophages (TAMs) improve outcome in solid tumors. Considerable differences are detected between leukemia-associated macrophages (LAMs) and TAMs. However, application to induce M1 characteristics in heterogeneous LAMs has not been established. Here we analyzed clinical relevance of macrophage phenotypes in human acute myeloid leukemia (AML), studied phenotypic evolution of bone marrow (BM) and spleen (SP) LAMs in mouse AML and T cell acute lymphoblastic leukemia (T-ALL) models, explored mechanism leading to different LAM phenotypes and tried to eliminate pro-leukemic effects by inducing M1 characteristics. The results showed that more M2-like LAMs but not total LAMs correlated with worse prognosis in AML patients. Heterogeneity of LAM activation in tissue-specific leukemic microenvironments was observed in both AML and ALL models, i.e. SP LAMs evolved with more M2 characteristics while BM LAMs with more M1 characteristics. Furthermore, IRF7 contributed to M1 characteristics through the activation of SAPK/JNK pathway. Moreover, targeting IRF7-SAPK/JNK pathway to induce M1 characteristics in LAMs contributed to prolonged survival in leukemia mice. Our study provides the potential target for macrophage based immuno-therapy strategy against leukemia.

PMID: 29632729 [PubMed]

https://ift.tt/2qpL8Po

Glioblastoma stem cell-derived exosomes induce M2 macrophages and PD-L1 expression on human monocytes.

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Glioblastoma stem cell-derived exosomes induce M2 macrophages and PD-L1 expression on human monocytes.

Oncoimmunology. 2018;7(4):e1412909

Authors: Gabrusiewicz K, Li X, Wei J, Hashimoto Y, Marisetty AL, Ott M, Wang F, Hawke D, Yu J, Healy LM, Hossain A, Akers JC, Maiti SN, Yamashita S, Shimizu Y, Dunner K, Zal MA, Burks JK, Gumin J, Nwajei F, Rezavanian A, Zhou S, Rao G, Sawaya R, Fuller GN, Huse JT, Antel JP, Li S, Cooper L, Sulman EP, Chen C, Geula C, Kalluri R, Zal T, Heimberger AB

Abstract
Exosomes can mediate a dynamic method of communication between malignancies, including those sequestered in the central nervous system and the immune system. We sought to determine whether exosomes from glioblastoma (GBM)-derived stem cells (GSCs) can induce immunosuppression. We report that GSC-derived exosomes (GDEs) have a predilection for monocytes, the precursor to macrophages. The GDEs traverse the monocyte cytoplasm, cause a reorganization of the actin cytoskeleton, and skew monocytes toward the immune suppresive M2 phenotype, including programmed death-ligand 1 (PD-L1) expression. Mass spectrometry analysis demonstrated that the GDEs contain a variety of components, including members of the signal transducer and activator of transcription 3 (STAT3) pathway that functionally mediate this immune suppressive switch. Western blot analysis revealed that upregulation of PD-L1 in GSC exosome-treated monocytes and GBM-patient-infiltrating CD14+ cells predominantly correlates with increased phosphorylation of STAT3, and in some cases, with phosphorylated p70S6 kinase and Erk1/2. Cumulatively, these data indicate that GDEs are secreted GBM-released factors that are potent modulators of the GBM-associated immunosuppressive microenvironment.

PMID: 29632728 [PubMed]

https://ift.tt/2EDUw6v

Survival gain in glioblastoma patients treated with dendritic cell immunotherapy is associated with increased NK but not CD8+ T cell activation in the presence of adjuvant temozolomide.

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Survival gain in glioblastoma patients treated with dendritic cell immunotherapy is associated with increased NK but not CD8+ T cell activation in the presence of adjuvant temozolomide.

Oncoimmunology. 2018;7(4):e1412901

Authors: Pellegatta S, Eoli M, Cuccarini V, Anghileri E, Pollo B, Pessina S, Frigerio S, Servida M, Cuppini L, Antozzi C, Cuzzubbo S, Corbetta C, Paterra R, Acerbi F, Ferroli P, DiMeco F, Fariselli L, Parati EA, Bruzzone MG, Finocchiaro G

Abstract
In a two-stage phase II study, 24 patients with first diagnosis of glioblastoma (GBM) were treated with dendritic cell (DC) immunotherapy associated to standard radiochemotherapy with temozolomide (TMZ) followed by adjuvant TMZ. Three intradermal injections of mature DC loaded with autologous GBM lysate were administered before adjuvant TMZ, while 4 injections were performed during adjuvant TMZ. According to a two-stage Simon design, to proceed to the second stage progression-free survival (PFS) 12 months after surgery was expected in at least 8 cases enrolled in the first stage. Evidence of immune response and interaction with chemotherapy were investigated. After a median follow up of 17.4 months, 9 patients reached PFS12. In these patients (responders, 37.5%), DC vaccination induced a significant, persistent activation of NK cells, whose increased response was significantly associated with prolonged survival. CD8+ T cells underwent rapid expansion and priming but, after the first administration of adjuvant TMZ, failed to generate a memory status. Resistance to TMZ was associated with robust expression of the multidrug resistance protein ABCC3 in NK but not CD8+ T cells. The negative effect of TMZ on the formation of T cell-associated antitumor memory deserves consideration in future clinical trials including immunotherapy.

PMID: 29632727 [PubMed]

https://ift.tt/2HffsG8

Modulation of CD8+ memory stem T cell activity and glycogen synthase kinase 3β inhibition enhances anti-tumoral immunity in gastric cancer.

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Modulation of CD8+ memory stem T cell activity and glycogen synthase kinase 3β inhibition enhances anti-tumoral immunity in gastric cancer.

Oncoimmunology. 2018;7(4):e1412900

Authors: Zhang JY, Zhao YL, Lv YP, Cheng P, Chen W, Duan M, Teng YS, Wang TT, Peng LS, Mao FY, Liu YG, Fu XL, Yu PW, Luo P, Zhang WJ, Zou QM, Zhuang Y

Abstract
The potential contributions of CD8+ memory stem T cells to anti-tumor immunity and immunotherapy responses in gastric cancer has not been demonstrated. We found that CD8+ memory stem T cell frequencies were increased in the peripheral blood of gastric cancer patients compared to healthy donors and declined in frequency with disease progression. Despite minimal in vitro cytotoxic activity, the adoptive transfer of CD8+ memory stem T cells into Rag1-/- tumor bearing mice enhanced tumor regression compared to CD8+ central or effector memory T cell counterparts. This effect was associated with an increase in splenic, draining lymph node and tumor infiltrating CD8+ T cell numbers and the development of an altered CD8+ T cell phenotype not seen during homeostasis. GSK-3β inhibition is known to promote memory stem T cell accumulation by arresting effector T cell differentiation in vivo. Surprisingly however, GSK-3β inhibition conversely increased the cytotoxic capacity of CD8+ memory stem T cells in vitro, and this was associated with the induction of effector T cell-associated effector proteins including FasL. Finally, FasL neutralization following GSK-3β inhibition directly attenuated the anti-tumoral capacity of CD8+ memory stem T cells both in vitro and in vivo. Altogether, our findings identify the therapeutic potential of modulating CD8+ memory stem T cells for improved anti-tumoral responses against gastric cancer.

PMID: 29632726 [PubMed]

https://ift.tt/2Hdmviz

SALL4 oncogene is an immunogenic antigen presented in various HLA-DR contexts.

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SALL4 oncogene is an immunogenic antigen presented in various HLA-DR contexts.

Oncoimmunology. 2018;7(4):e1412030

Authors: Kroemer M, Spehner L, Mercier-Letondal P, Boullerot L, Kim S, Jary M, Galaine J, Picard E, Ferrand C, Nguyen T, Larosa F, Adotévi O, Godet Y, Borg C

Abstract
Purpose: To investigate the immunoprevalence of SALL4-derived peptides in healthy volunteers and cancer patients. Experimental Design: A multistep approach including prediction algorithms was used to design in silico SALL4-derived peptides theoretically able to bind on common HLA-DR and HLA-A/B molecules. The presence of T-cell responses after a long term T-cell assay (28 days) against SALL4 was monitored in 14 healthy donors and the presence of T-cell responses after a short term T-cell assay (10 days) was monitored in 67 cancer patients using IFN-γ ELISPOT assay. A T-cell clone specific for the immunoprevalent A18 K-derived peptide was isolated, characterized and used as a tool to characterize the natural processing of A18 K. Results: A SALL4 specific T-cell repertoire was present in healthy donors (8/14) and cancer patients (29/67) after short term T-cell assay. We further identified two immunoprevalant SALL4-derived peptides, R18 A and A18 K, which bind MHC-class II. In parallel, an A18 K specific Th1 clone recognized monocyte derived Dendritic Cell (moDC) loaded with SALL4 containing cell lysate. The level of IFN-γ secreted by specific T-cell clone was greater in presence of moDC loaded with SALL4 containing cell lysate (49.23 ± 14.02%) than with moDC alone (18.03 ± 3.072%) (p = 0.0477) Conclusion: These results show for the first time immunogenicity of SALL4 oncogenic protein-derived peptides, especially A18 K and R18 A peptides and make them potential targets for personalized medicine. Thus, SALL4 possess major characteristics of a tumor antigen.

PMID: 29632725 [PubMed]

https://ift.tt/2IOcSnV

Improved migration of tumor ascites lymphocytes to ovarian cancer microenvironment by CXCR2 transduction.

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Improved migration of tumor ascites lymphocytes to ovarian cancer microenvironment by CXCR2 transduction.

Oncoimmunology. 2018;7(4):e1412029

Authors: Idorn M, Olsen M, Halldórsdóttir HR, Skadborg SK, Pedersen M, Høgdall C, Høgdall E, Met Ö, Thor Straten P

Abstract
Chemokines are essential mediators of cellular trafficking, interactions and tumor development. Though adoptive cell therapy (ACT) has been a tremendous success in the treatment of metastatic melanoma (MM), a major obstacle for successful ACT, is limited homing of effector T cells to immune suppressive tumor sites. We hypothesized that equipping T cells with chemokine receptors matching the chemokines of the tumor microenvironment, could improve tumor homing of T cells. T cells from malignant ascites (n = 13); blood from ovarian cancer (OC) patients (n = 14); and healthy donors (n = 13) were analyzed by flow cytometry. We found that FoxP3+ regulatory T cells accumulation in patients with OC associates with CCR4 expression. We characterized a chemokine profile of ascites chemokines, and expression of corresponding receptors on circulating T cells and tumor ascites lymphocytes (TALs). CCL22, CXCL9, CXCL10 and CXCL12 associated with enrichment of CCR4+, CCR5+, CXCR3+ and CXCR4+ T cells in ascites. Circulating T cells and TALs however did not express CXCR2, identifying CXCR2 as candidate for chemokine receptor transduction. TALs readily expressed IFNγ and TNFα upon stimulation despite the frequency decreasing with in vitro expansion. Lentiviral transduction of TALs (n = 4) with chemokine receptor CXCR2 significantly increased transwell migration of TALs towards rhIL8 and autologous ascites. The majority of expanded and transduced TALs were of a T effector memory subtype. This proof of concept study shows that chemokine receptor engineering with CXCR2 is feasible and improves homing of transduced TALs towards the OC microenvironment.

PMID: 29632724 [PubMed]

https://ift.tt/2GPFWun

Enhanced protection of C57 BL/6 vs Balb/c mice to melanoma liver metastasis is mediated by NK cells.

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Enhanced protection of C57 BL/6 vs Balb/c mice to melanoma liver metastasis is mediated by NK cells.

Oncoimmunology. 2018;7(4):e1409929

Authors: Foerster F, Boegel S, Heck R, Pickert G, Rüssel N, Rosigkeit S, Bros M, Strobl S, Kaps L, Aslam M, Diken M, Castle J, Sahin U, Tuettenberg A, Bockamp E, Schuppan D

Abstract
The B16F10 murine melanoma cell line displays a low expression of MHC class I molecules favoring immune evasion and metastases in immunocompetent C57 BL/6 wild-type mice. Here, we generated metastases to the liver, an organ that is skewed towards immune tolerance, by intrasplenic injection of B16F10 cells in syngeneic C57 BL/6 compared to allogeneic Balb/c mice. Surprisingly, Balb/c mice, which usually display a pronounced M2 macrophage and Th2 T cell polarization, were ∼3 times more susceptible to metastasis than C57 BL/6 mice, despite a much higher M1 and Th1 T cell immune response. The anti-metastatic advantage of C57 BL/6 mice could be attributed to a more potent NK-cell mediated cytotoxicity against B16F10 cells. Our findings highlight the role of NK cells in innate anti-tumor immunity in the context of the liver - particularly against highly aggressive MHC I-deficient cancer cells. Moreover, the B16F10 model of melanoma liver metastasis is suited for developing novel therapies targeting innate NK cell related immunity in liver metastases and liver cancer.

PMID: 29632723 [PubMed]

https://ift.tt/2EHndzy

NK cell activation and recovery of NK cell subsets in lymphoma patients after obinutuzumab and lenalidomide treatment.

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NK cell activation and recovery of NK cell subsets in lymphoma patients after obinutuzumab and lenalidomide treatment.

Oncoimmunology. 2018;7(4):e1409322

Authors: Vo DN, Alexia C, Allende-Vega N, Morschhauser F, Houot R, Menard C, Tarte K, Cartron G, Villalba M

Abstract
Obinutuzumab (OBZ) shows stronger antibody-dependent cell cytotoxicity (ADCC) compared to rituximab and improved clinical activity for treating certain CD20+ neoplasia. However, the efficacy of monoclonal antibody (mAb) as a monotherapy is limited. Natural Killer (NK) cells are mediators of ADCC. Hematological cancer patients possess antitumor NK cells that are unable to control disease, possibly because they are dysfunctional. The immunomodulatory drug lenalidomide (LEN) could be a treatment to restore exhausted NK cell cytotoxic functions. The clinical trial GALEN is a Phase Ib/II study of OBZ combined with LEN for the treatment of relapsed/refractory follicular and aggressive (DLBCL and MCL) B-cell Lymphoma. During treatment, we analyzed specific aspects of NK cell biology. Treatment reversed the immature NK phenotype of patients and increased expression of NK activating receptors. Inhibitory receptors were either unchanged or decreased. There was a strong NK response at the end of the 1st cycle: NK number and intracellular granzyme B (GrzB) expression decreased, degranulation increased and NK responded better to allogeneic target challenge. Moreover, the interaction of NK cells with B cell targets, measured by trogocytosis, decreased during treatment. At the end of treatment, when target cells had been wiped out, the proportion of reactive NK cells (CD69+, CD45RARO+, CD107a+, CD19+) strongly decreased. Because all patients received LEN and OBZ, it was uncertain which drug was responsible of our observations, or even if a combination of both products was necessary for the described effects on this lymphocyte lineage.

PMID: 29632722 [PubMed]

https://ift.tt/2HrNzIv

The Toll like receptor 4 ligand cold-inducible RNA-binding protein as vaccination platform against cancer.

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The Toll like receptor 4 ligand cold-inducible RNA-binding protein as vaccination platform against cancer.

Oncoimmunology. 2018;7(4):e1409321

Authors: Villanueva L, Silva L, Llopiz D, Ruiz M, Iglesias T, Lozano T, Casares N, Hervas-Stubbs S, Rodríguez MJ, Carrascosa JL, Lasarte JJ, Sarobe P

Abstract
Tumor infiltrating lymphocytes have been associated with a better prognostic and with higher response rates in patients treated with checkpoint inhibiting antibodies, suggesting that strategies promoting tumor inflammation may enhance the efficacy of these currently available therapies. Our aim was thus to develop a new vaccination platform based on cold-inducible RNA binding protein (CIRP), an endogenous TLR4 ligand generated during inflammatory processes, and characterize whether it was amenable to combination with checkpoint inhibitors. In vitro, CIRP induced dendritic cell activation, migration and enhanced presentation of CIRP-bound antigens to T-cells. Accordingly, antigen conjugation to CIRP conferred immunogenicity, dependent on immunostimulatory and antigen-targeting capacities of CIRP. When applied in a therapeutic setting, vaccination led to CD8-dependent tumor rejection in several tumor models. Moreover, immunogenicity of this vaccination platform was enhanced not only by combination with additional adjuvants, but also with antibodies blocking PD-1/PD-L1, CTLA-4 and IL-10, immunosuppressive molecules usually present in the tumor environment and also induced by the vaccine. Therefore, priming with a CIRP-based vaccine combined with immune checkpoint-inhibiting antibodies rejected established B16-OVA tumors. Finally, equivalent activation and T-cell stimulatory effects were observed when using CIRP in vitro with human cells, suggesting that CIRP-based vaccination strategies could be a valuable clinical tool to include in combinatorial immunotherapeutic strategies in cancer patients.

PMID: 29632721 [PubMed]

https://ift.tt/2qpL2Y2

Blockade of Tumor-Expressed PD-1 promotes lung cancer growth.

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Blockade of Tumor-Expressed PD-1 promotes lung cancer growth.

Oncoimmunology. 2018;7(4):e1408747

Authors: Du S, McCall N, Park K, Guan Q, Fontina P, Ertel A, Zhan T, Dicker AP, Lu B

Abstract
Anti-PD-1 immunotherapy is the standard of care for treating many patients with non-small cell lung cancer (NSCLC), yet mechanisms of treatment failure are emerging. We present a case of NSCLC, who rapidly progressed during a trial (NCT02318771) combining palliative radiotherapy and pembrolizumab. Planned tumor biopsy demonstrated PD-1 expression by NSCLC cells. We validated this observation by detecting PD-1 transcript in lung cancer cells and by co-localizing PD-1 and lung cancer-specific markers in resected lung cancer tissues. We further investigated the biological role of cancer-intrinsic PD-1 in a mouse lung cancer cell line, M109. Knockout or antibody blockade of PD-1 enhanced M109 viability in-vitro, while PD-1 overexpression and exposure to recombinant PD-L1 diminished viability. PD-1 blockade accelerated growth of M109-xenograft tumors with increased proliferation and decreased apoptosis in immune-deficient mice. This represents a first-time report of NSCLC-intrinsic PD-1 expression and a potential mechanism by which PD-1 blockade may promote cancer growth.

PMID: 29632720 [PubMed]

https://ift.tt/2EF7BfE

The ethical and deontological charter of the French faculties of medicine and odontology

Publication date: Available online 10 April 2018
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): O. Laccourreye, H. Maisonneuve




https://ift.tt/2HgLwJS

One last Who am I!

Publication date: Available online 10 April 2018
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): O. Laccourreye, A. Werner, I. McGill




https://ift.tt/2v5WhK5

Working Towards a Common Transatlantic Approach for Evaluation of Exercise-Induced Laryngeal Obstruction.

Related Articles

Working Towards a Common Transatlantic Approach for Evaluation of Exercise-Induced Laryngeal Obstruction.

Immunol Allergy Clin North Am. 2018 May;38(2):281-292

Authors: Røksund OD, Olin JT, Halvorsen T

Abstract
Exertional dyspnea can be a manifestation of dysfunction in a variety of organ systems. Exercise-induced laryngeal obstruction (EILO), a condition previously known as vocal cord dysfunction and paradoxic vocal fold motion, is defined as inappropriate, reversible narrowing of the larynx during vigorous exercise. EILO is usually characterized by typical symptoms, which nevertheless frequently are confused with those of other conditions, including asthma. Laryngoscopy performed as symptoms evolve from rest to peak exercise is pivotal in patient work-up. Moving forward, laryngoscopy findings that definitively characterize EILO need to be defined as do objective measures that can quantitate absolute laryngeal measurements during exercise.

PMID: 29631736 [PubMed - in process]

https://ift.tt/2qovgwO

Exercise and the Total Airway: A Call to Action.

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Exercise and the Total Airway: A Call to Action.

Immunol Allergy Clin North Am. 2018 May;38(2):xv-xix

Authors: Olin JT, Hull JH

PMID: 29631744 [PubMed - in process]

https://ift.tt/2Hdijzl

Food Allergy Point of Care Pearls.

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Food Allergy Point of Care Pearls.

Immunol Allergy Clin North Am. 2018 May;38(2):e1-e8

Authors: Bird JA

Abstract
Food allergy should be suspected in individuals with a history of immediate reactivity following ingestion (ie, typically within 20 minutes and almost always within 2 hours) with typical symptoms of immunoglobulin E-mediated reactivity (eg, urticaria, angioedema, coughing, wheezing, vomiting). Testing for food allergy should focus on the most likely allergen to provoke the reaction based on the patient's history. Safe introduction of peanut-containing foods into the diet of an infant at high risk of developing peanut allergy at 4 to 6 months is likely to reduce the risk of peanut allergy.

PMID: 29631742 [PubMed - in process]

https://ift.tt/2qpEMzw

The Future of Exertional Respiratory Problems: What Do We Know About the Total Airway Approach and What Do We Need to Know?

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The Future of Exertional Respiratory Problems: What Do We Know About the Total Airway Approach and What Do We Need to Know?

Immunol Allergy Clin North Am. 2018 May;38(2):333-339

Authors: Olin JT, Hull JH

Abstract
Exercise is increasingly viewed as a preventative and therapeutic modality for medical and behavioral health disorders. Therefore, it is imperative that the medical and scientific communities minimize barriers that discourage exercise. This issue of Immunology and Allergy Clinics of North America details a "total airway approach" to the evaluation of exertional respiratory problems. Reviews guide clinicians through evaluation and therapy. Moving forward, there is much room for growth with respect to research in each of these areas as well as for common inflammatory pathways and neurophysiologic coupling across all airway segments.

PMID: 29631741 [PubMed - in process]

https://ift.tt/2v9igQt

Exertional Dyspnea and Excessive Dynamic Airway Collapse.

Related Articles

Exertional Dyspnea and Excessive Dynamic Airway Collapse.

Immunol Allergy Clin North Am. 2018 May;38(2):325-332

Authors: Morris MJ, Woods JT, McLaughlin CW

Abstract
Excessive dynamic airway collapse is a relatively new diagnosis separate from tracheobronchomalacia that is manifested by functional collapse of the large airways. Most commonly described in patients with underlying obstructive lung disease such as chronic obstructive pulmonary disease and asthma, it may contribute to increased dyspnea, cough, or exacerbations. There are few data published on the role of excessive dynamic airway collapse as related specifically to exercise. It was recently described as the cause for exertional dyspnea in individuals without underlying lung disease.

PMID: 29631740 [PubMed - in process]

https://ift.tt/2H9ZrBx

Surgical Intervention for Exercise-Induced Laryngeal Obstruction.

Related Articles

Surgical Intervention for Exercise-Induced Laryngeal Obstruction.

Immunol Allergy Clin North Am. 2018 May;38(2):317-324

Authors: Heimdal JH, Maat R, Nordang L

Abstract
Respiratory distress during exercise can be caused by exercise-induced laryngeal obstruction (EILO). The obstruction may appear at the level of the laryngeal inlet (supraglottic), similar to supraglottic collapse observed in infants with congenital laryngomalacia (CLM). This observation has encouraged surgeons to treat supraglottic EILO with procedures proven efficient for severe CLM. This article summarizes key features of the published experience related to surgical treatment of EILO. Supraglottoplasty is an irreversible procedure with potential complications. Surgery should be restricted to cases where the supraglottic laryngeal obstruction significantly affects the quality of life in patients for whom conservative treatment modalities have failed.

PMID: 29631739 [PubMed - in process]

https://ift.tt/2vedmSn

Exercise-Induced Laryngeal Obstruction and Performance Psychology: Using the Mind as a Diagnostic and Therapeutic Target.

Related Articles

Exercise-Induced Laryngeal Obstruction and Performance Psychology: Using the Mind as a Diagnostic and Therapeutic Target.

Immunol Allergy Clin North Am. 2018 May;38(2):303-315

Authors: Olin JT, Westhoff Carlson E

Abstract
Exercise-induced laryngeal obstruction causes severe shortness of breath during exercise. Episodes are associated with severe distress. These patients and those with inducible laryngeal obstruction triggered by other factors have been noted to demonstrate mental health disorders, personality features that may be associated with symptoms, and dysfunctional stress responses. This literature review calls attention to the observation that patients with isolated exercise-induced laryngeal obstruction are generally mentally healthy. We review available metrics to assess traits and stress responses in performance psychology. We also discuss a therapeutic performance psychology framework.

PMID: 29631738 [PubMed - in process]

https://ift.tt/2HhNVEa

Speech-Language Pathology as a Primary Treatment for Exercise-Induced Laryngeal Obstruction.

Related Articles

Speech-Language Pathology as a Primary Treatment for Exercise-Induced Laryngeal Obstruction.

Immunol Allergy Clin North Am. 2018 May;38(2):293-302

Authors: Shaffer M, Litts JK, Nauman E, Haines J

Abstract
Exercise-induced laryngeal obstruction is a condition that restricts respiration during exercise via inappropriate glottic or supraglottic obstruction. The literature supports behavioral treatment provided by a speech-language pathologist as an effective means of treating exercise-induced laryngeal obstruction. Treatment includes educating the patient, training on relaxation, instruction on paced exercise, and use of various breathing techniques to optimize laryngeal aperture. Intervention for patients with exercise-induced laryngeal obstruction may be delivered by a speech-language pathologist, given their clinical skill of facilitating long-term behavioral change and expertise in the laryngeal mechanism.

PMID: 29631737 [PubMed - in process]

https://ift.tt/2EEj2Er

Exercise-Induced Laryngeal Obstruction-An Overview.

Related Articles

Exercise-Induced Laryngeal Obstruction-An Overview.

Immunol Allergy Clin North Am. 2018 May;38(2):271-280

Authors: Nordang L, Norlander K, Walsted ES

Abstract
Exertional dyspnea is common in health and disease. Despite having known for centuries that breathlessness can arise from the larynx, exercise-induced laryngeal obstruction is a more prevalent condition than previously assumed. This article provides a brief overview of the history, epidemiology, and pathophysiology of exercise-induced laryngeal obstruction.

PMID: 29631735 [PubMed - in process]

https://ift.tt/2HcLN0p

Exercise and Sinonasal Disease.

Related Articles

Exercise and Sinonasal Disease.

Immunol Allergy Clin North Am. 2018 May;38(2):259-269

Authors: Steelant B, Hox V, Hellings PW, Bullens DM, Seys SF

Abstract
Physical exercise requires proper function of the upper and lower airways in order to meet exertional ventilatory requirements. Athletes performing frequent intensive exercise experience more sino-nasal symptoms and demonstrate objective decreases in sino-nasal function when compared with the general population. Sino-nasal dysfunction is known to interfere with sport performance. Nasal epithelial injury, neutrophilic influx, and decreased mucociliary clearance have been associated with intensive training. In this review, the authors provide a comprehensive overview of the prevalence of sino-nasal disease in athletes, the possible underlying pathophysiologic mechanisms, and a summary of diagnostic and treatment options.

PMID: 29631734 [PubMed - in process]

https://ift.tt/2qpwtE9

Nonpharmacologic Strategies to Manage Exercise-Induced Bronchoconstriction.

Related Articles

Nonpharmacologic Strategies to Manage Exercise-Induced Bronchoconstriction.

Immunol Allergy Clin North Am. 2018 May;38(2):245-258

Authors: Dickinson J, Amirav I, Hostrup M

Abstract
Pharmacologic management of exercise-induced bronchoconstriction (EIB) is the mainstay of preventative therapy. There are some nonpharmacologic interventions, however, that may assist the management of EIB. This review discusses these nonpharmacologic interventions and how they may be applied to patients and athletes with EIB.

PMID: 29631733 [PubMed - in process]

https://ift.tt/2IO1vfv

Pharmacologic Strategies for Exercise-Induced Bronchospasm with a Focus on Athletes.

Related Articles

Pharmacologic Strategies for Exercise-Induced Bronchospasm with a Focus on Athletes.

Immunol Allergy Clin North Am. 2018 May;38(2):231-243

Authors: Backer V, Mastronarde J

Abstract
Exercise-induced bronchoconstriction (EIB) is the transient narrowing of the airways during and after exercise that occurs in response to increased ventilation in susceptible individuals. It occurs across the age spectrum in patients with underlying asthma and can occur in athletes without baseline asthma. The inflammatory mechanisms underlying EIB in patients without asthma may be distinct from those underlying EIB in patients with asthma. This review summarizes mechanistic and clinical data that can guide the choice of chronic and acute pharmacologic therapies targeting control of EIB. Relevant regulations from the World Anti-Doping Agency are also discussed.

PMID: 29631732 [PubMed - in process]

https://ift.tt/2IM4kxK

Testing for Exercise-Induced Bronchoconstriction.

Related Articles

Testing for Exercise-Induced Bronchoconstriction.

Immunol Allergy Clin North Am. 2018 May;38(2):215-229

Authors: Brannan JD, Porsbjerg C

Abstract
Exercise-induced bronchoconstriction (EIB) is a form of airway hyperresponsiveness that occurs with or without current symptoms of asthma. EIB is an indicator of active and treatable pathophysiology in persons with asthma. The objective documentation of EIB permits the identification of an individual who may be at risk during a recreational sporting activity or when exercising as an occupational duty. EIB can be identified with laboratory exercise testing or surrogate tests for EIB. These include eucapnic voluntary hyperpnea and osmotic stimuli (eg, inhaled mannitol) and offer improved diagnostic sensitivity to identify EIB and improved standardization when compared with laboratory exercise.

PMID: 29631731 [PubMed - in process]

https://ift.tt/2qpEloS

Exercise-Induced Bronchoconstriction: Background, Prevalence, and Sport Considerations.

Related Articles

Exercise-Induced Bronchoconstriction: Background, Prevalence, and Sport Considerations.

Immunol Allergy Clin North Am. 2018 May;38(2):205-214

Authors: Bonini M, Silvers W

Abstract
The transient airway narrowing that occurs as a result of exercise is defined as exercise-induced bronchoconstriction (EIB). The prevalence of EIB has been reported to be up to 90% in asthmatic patients, reflecting the level of disease control. However, EIB may develop even in subjects without clinical asthma, particularly in children, athletes, patients with atopy or rhinitis, and following respiratory infections. The intensity, duration, and type of training have been associated with the occurrence of EIB. In athletes, EIB seems to be only partly reversible, and exercise seems to be a causative factor of airway inflammation and symptoms.

PMID: 29631730 [PubMed - in process]

https://ift.tt/2EFlzOJ

Exercise-Induced Bronchoconstriction and the Air We Breathe.

Related Articles

Exercise-Induced Bronchoconstriction and the Air We Breathe.

Immunol Allergy Clin North Am. 2018 May;38(2):183-204

Authors: Rundell KW, Smoliga JM, Bougault V

Abstract
An association between airway dysfunction and airborne pollutant inhalation exists. Volatilized airborne fluorocarbons in ski wax rooms, particulate matter, and trichloromines in indoor environments are suspect to high prevalence of exercise-induced bronchoconstriction and new-onset asthma in athletes competing in cross-country skiing, ice rink sports, and swimming. Ozone is implicated in acute decreases in lung function and the development of new-onset asthma from exposure during exercise. Mechanisms and genetic links are proposed for pollution-related new-onset asthma. Oxidative stress from airborne pollutant inhalation is a common thread to progression of airway damage. Key pollutants and mechanisms for each are discussed.

PMID: 29631729 [PubMed - in process]

https://ift.tt/2HkKSea

Mechanisms and Biomarkers of Exercise-Induced Bronchoconstriction.

Related Articles

Mechanisms and Biomarkers of Exercise-Induced Bronchoconstriction.

Immunol Allergy Clin North Am. 2018 May;38(2):165-182

Authors: Kippelen P, Anderson SD, Hallstrand TS

Abstract
Exercise is a common trigger of bronchoconstriction. In recent years, there has been increased understanding of the pathophysiology of exercise-induced bronchoconstriction. Although evaporative water loss and thermal changes have been recognized stimuli for exercise-induced bronchoconstriction, accumulating evidence points toward a pivotal role for the airway epithelium in orchestrating the inflammatory response linked to exercise-induced bronchoconstriction. Overproduction of inflammatory mediators, underproduction of protective lipid mediators, and infiltration of the airways with eosinophils and mast cells are all established contributors to exercise-induced bronchoconstriction. Sensory nerve activation and release of neuropeptides maybe important in exercise-induced bronchoconstriction, but further research is warranted.

PMID: 29631728 [PubMed - in process]

https://ift.tt/2EDWt2R

Study on sandstorm PM 10 exposure assessment in the large-scale region: a case study in Inner Mongolia

Abstract

The current exposure-effect curves describing sandstorm PM₁₀ exposure and the health effects are drawn roughly by the outdoor concentration (OC), which ignored the exposure levels of people's practical activity sites. The main objective of this work is to develop a novel approach to quantify human PM₁₀ exposure by their socio-categorized micro-environment activities-time weighed (SCMEATW) in strong sandstorm period, which can be used to assess the exposure profiles in the large-scale region. Types of people's SCMEATW were obtained by questionnaire investigation. Different types of representatives were trackly recorded during the big sandstorm. The average exposure levels were estimated by SCMEATW. Furthermore, the geographic information system (GIS) technique was taken not only to simulate the outdoor concentration spatially but also to create human exposure outlines in a visualized map simultaneously, which could help to understand the risk to different types of people. Additionally, exposure-response curves describing the acute outpatient rate odds by sandstorm were formed by SCMEATW, and the differences between SCMEATW and OC were compared. Results indicated that acute outpatient rate odds had relationships with PM₁₀ exposure from SCMEATW, with a level less than that of OC. Some types of people, such as herdsmen and those people walking outdoors during a strong sandstorm, have more risk than office men. Our findings provide more understanding of human practical activities on their exposure levels; they especially provide a tool to understand sandstorm PM₁₀ exposure in large scale spatially, which might help to perform the different categories population's risk assessment regionally.

https://ift.tt/2qskAMH

Natural killer cells target and differentiate cancer stem-like cells/undifferentiated tumors: strategies to optimize their growth and expansion for effective cancer immunotherapy

Kawaljit Kaur | Milica Perišic Nanut | Meng-Wei Ko | Tahmineh Safaie | Janko Kos | Anahid Jewett

https://ift.tt/2HuVPb0

Bedside ultrasonography as an alternative to computed tomography scan for the measurement of optic nerve sheath diameter

Uday Yanamandra, Amul Gupta, Sushma Yanamandra, Subrat Kumar Das, Sagarika Patyal, Velu Nair

Journal of Neurosciences in Rural Practice 2018 9(2):252-255

Background: Optic nerve sheath diameter (ONSD) as measured by optic nerve sheath ultrasonography (ONSU) is used as a surrogate marker of intracranial pressure (ICP), especially in resource-limited settings. There is a growing interest in the use of ONSU in emergency and high-altitude setups. Notwithstanding multiple studies done on this subject, there is a paucity of data regarding standardization of techniques and comparison of ONSU with computed tomography (CT). Materials and Methods: Thirty-five patients with a diagnosis of high-altitude cerebral edema were enrolled in the study. ONSD was measured in all patients using ONSU, along visual and coronal axis, and CT scan. We repeated ONSU in these patients on days 3, 7, 10, and 15 (day of discharge). Correlation between visual and coronal axis as well as CT scan was analyzed. Results: The correlation of visual to coronal and coronal to visual was equally significant (both correlation coefficients being R2 = 0.983). Correlation of ONSD by visual axis to CT scan was better than coronal axis (correlation coefficient R2 = 0.986 vs. 0.96, respectively). Conclusion: In our study, we found a strong correlation between the visual and coronal axes. Thus, either of the two axes can be used for monitoring ICP. However, it has been found that measurements along the coronal axis are challenging, especially in the emergency setup. ONSD measured along visual axis correlated better with CT scan as compared to the coronal axis.

https://ift.tt/2EEQHxN

Cranial gravitational (falling) bullet injuries: Point of view

Husain A Abdali, Samer S Hoz, Luis Rafael Moscote-Salazar

Journal of Neurosciences in Rural Practice 2018 9(2):278-280



https://ift.tt/2qpriUJ

Postdecompressive craniectomy surgery, ventriculomegaly, or hydrocephalus development: imaging, prevention, and management

Guru Dutta Satyarthee

Journal of Neurosciences in Rural Practice 2018 9(2):177-179



https://ift.tt/2EFlkTF

Repeated peritoneal catheter blockage caused by neurocysticercosis following ventriculoperitoneal shunt placement for hydrocephalus

Zhi Hua Li, Zhong Quan Wang, Jing Cui, Fu You Guo

Journal of Neurosciences in Rural Practice 2018 9(2):268-271

Cerebral cysticercosis is common, but the possibility for repeated occurrence of peritoneal catheter blockage caused by neurocysticercosis (NCC) after two revisions following ventriculoperitoneal shunt placement for hydrocephalus is unusual. Herein, we describe one rare case in which peritoneal catheter revision was performed two times unsuccessfully. Endoscopic cysternostomy rather than peritoneal catheter adjustment was performed successfully, and histopathological examination of excised cystic samples confirmed NCC in our hospital. The present case highlights the need for awareness of NCC as a possible etiology of hydrocephalus, especially in developing countries. Uncommon findings in both lateral ventricles following low-field magnetic resonance imaging scans as well as the rarity of this infection involved in unusual location play important roles in misdiagnosis and incorrect treatment for hydrocephalus; thus, endoscopic cysternostomy, rather than multiple shunt adjustment of the peritoneal end, is recommended in the selected patient. To the best of our knowledge, this is the first report describing the misdiagnosis and inappropriate treatment of hydrocephalus caused by cerebral cysticercosis in China.

https://ift.tt/2qnZwYA