Experimental surgery as part of the development of degradable biomaterials for cardiovascular surgery

Introduction: Cardiovascular diseases are responsible for significant morbidity and mortality in the population. Artificial vascular grafts are often essential for surgical procedures in radical or palliative treatment. Many new biodegradable materials are currently under development. Preclinical testing of each new material is imperative, both in vitro and in vivo, and therefore animal experiments are still a necessary part of the testing process before any clinical use. The aim of this paper is to present the options of using various experimental animal models in the field of cardiovascular surgery including their extrapolation to clinical medicine. Methods: The authors present their general experience in the field of experimental surgery. They discuss the selection process of an optimal experimental animal model to test foreign materials for cardiovascular surgery and of an optimal region for implantation. Results: The authors present rat, rabbit and porcine models as optimal experimental animals for material hemocompatibility and degradability testing. Intraperitoneal implantation in the rat is a simple and feasible procedure, as well as aortic banding in the rabbit or pig. The carotid arteries can also be used, as well. Porcine pulmonary artery banding is slightly more difficult with potential complications. The banded vessels, explanted after a defined time period, are suitable for further mechanical testing using biomechanical analyses, for example, the inflation-extension test. Conclusion: An in vivo experiment cannot be avoided in the last phases of preclinical research of new materials. However, we try to strictly observe the 3R concept ­ Replacement, Reduction and Refinement; in line with this concept, the potential of each animal should be used as much as possible to reduce the number of animals.

Temporal changes in total and metabolically active ruminal methanogens in dairy cows supplemented with 3-nitrooxypropanol.

The purpose of this study was to investigate the effect of 3-nitrooxypropanol (3-NOP), a potent methane inhibitor, on total and metabolically active methanogens in the rumen of dairy cows over the course of the day and over a 12-wk period. Rumen contents of 8 ruminally cannulated early-lactation dairy cows were sampled at 2, 6, and 10 h after feeding during wk 4, 8, and 12 of a randomized complete block design experiment in which 3-NOP was fed at 60 mg/kg of feed dry matter. Cows (4 fed the control and 4 fed the 3-NOP diet) were blocked based on their previous lactation milk yield or predicted milk yield. Rumen samples were extracted for microbial DNA (total) and microbial RNA (metabolically active), PCR amplified for the 16S rRNA gene of archaea, sequenced on an Illumina platform, and analyzed for archaea diversity. In addition, the 16S copy number and 3 ruminal methanogenic species were quantified using the real-time quantitative PCR assay. We detected a difference between DNA and RNA (cDNA)-based archaea communities, revealing that ruminal methanogens differ in their metabolic activities. Within DNA and cDNA components, methanogenic communities differed by sampling hour, week, and treatment. Overall, Methanobrevibacter was the dominant genus (94.3%) followed by Methanosphaera, with the latter genus having greater abundance in the cDNA component (14.5%) compared with total populations (5.5%). Methanosphaera was higher at 2 h after feeding, whereas Methanobrevibacter increased at 6 and 10 h in both groups, showing diurnal patterns among individual methanogenic lineages. Methanobrevibacter was reduced at wk 4, whereas Methanosphaera was reduced at wk 8 and 12 in cows supplemented with 3-NOP compared with control cows, suggesting differential responses among methanogens to 3-NOP. A reduction in Methanobrevibacter ruminantium in all 3-NOP samples from wk 8 was confirmed using real-time quantitative PCR. The relative abundance of individual methanogens was driven by a combination of dietary composition, dry matter intake, and hydrogen concentrations in the rumen. This study provides novel information on the effects of 3-NOP on individual methanogenic lineages, but further studies are needed to understand temporal dynamics and to validate the effects of 3-NOP on individual lineages of ruminal methanogens.

Enteric methane emission, milk production, and composition of dairy cows fed 3-nitrooxypropanol.

This study examined the effect of 3-nitrooxypropanol (3-NOP), an investigational substance, on enteric methane emission, milk production, and composition in Holstein dairy cows. Following a 3-wk covariate period, 48 multi- and primiparous cows averaging (± standard deviation) 118 ± 28 d in milk, 43.4 ± 8 kg/d milk yield, and 594 ± 57 kg of body weight were blocked based on days in milk, milk yield, and enteric methane emission and randomly assigned to 1 of 2 treatment groups: (1) control, no 3-NOP, and (2) 3-NOP applied at 60 mg/kg feed dry matter. Inclusion of 3-NOP was through the total mixed ration and fed for 15 consecutive weeks. Cows were housed in a freestall barn equipped with a Calan Broadbent Feeding System (American Calan Inc., Northwood, NH) for monitoring individual dry matter intake and fed ad libitum once daily. Enteric gaseous emissions (methane, carbon dioxide, and hydrogen) were measured using 3 GreenFeed (C-Lock Inc., Rapid City, SD) units. Dry matter intake, cow body weight, and body weight change were not affected by 3-NOP. Compared with the control group, 3-NOP applied at 60 mg/kg feed dry matter decreased daily methane emission, emission yield, and emission intensity by 26, 27, and 29%, respectively. Enteric emission of carbon dioxide was not affected, and hydrogen emission was increased 6-fold by 3-NOP. Administration of 3-NOP had no effect on milk and energy-corrected milk yields and feed efficiency, increased milk fat and milk urea nitrogen concentrations, and increased milk fat yield but had no other effects on milk components. Concentration of C6:0 and C8:0 and the sum of saturated fatty acids in milk fat were increased by 3-NOP. Total trans fatty acids and the sum of polyunsaturated fatty acids were decreased by 3-NOP. In this experiment, 3-NOP decreased enteric methane daily emission, yield, and intensity without affecting dry matter intake and milk yield, but increased milk fat in high-producing dairy cows.

Reducing enteric methane emissions from dairy cattle: Two ways to supplement 3-nitrooxypropanol.

The aim of this work was to determine the effect of 3-nitrooxypropanol (3-NOP) on the enteric methane (CH4) emissions and performance of lactating dairy cows when mixed in with roughage or incorporated into a concentrate pellet. After 2 pretreatment weeks without 3-NOP supplementation, 30 Holstein Friesian cows were divided into 3 homogeneous treatment groups: no additive, 3-NOP mixed in with the basal diet (roughage; NOPbas), and 3-NOP incorporated into a concentrate pellet (NOPconc). The pretreatment period was followed by a 10-wk treatment period in which the NOPbas and NOPconc cows were fed 1.6 g of 3-NOP/cow per day. After the treatment period, a 2-wk washout period followed without 3-NOP supplementation. The CH4 emissions were measured using a GreenFeed unit (C-Lock Inc., Rapid City, SD) installed in a freestall with cubicles during the entire experimental period. On average for the total treatment period and compared with the no-additive group, CH4 production (g/d) was 28 and 23% lower for NOPbas and NOPconc, respectively. Methane yield (g/kg of dry matter intake) and methane intensity (g/kg of milk) were 23 and 24% lower for NOPbas, respectively, and 21 and 22% lower for NOPconc, respectively. No differences were found between NOPbas and NOPconc. Moreover, supplying 3-NOP did not affect total dry matter intake, milk production, or milk composition. The results of this experiment show that 3-NOP can reduce enteric CH4 emissions of dairy cattle when incorporated into a concentrate pellet and that this reduction is not different from the effect of mixing in 3-NOP with the basal diet (roughage). This broadens the possibilities for using 3-NOP in the dairy sector worldwide, as it is not always feasible to provide an additive mixed in with the basal diet.

Effect of 3-nitrooxypropanol on methane and hydrogen emissions, methane isotopic signature, and ruminal fermentation in dairy cows.

The objective of this crossover experiment was to investigate the effect of a methane inhibitor, 3-nitrooxypropanol (3NOP), on enteric methane emission, methane isotopic composition, and rumen fermentation and microbial profile in lactating dairy cows. The experiment involved 6 ruminally cannulated late-lactation Holstein cows assigned to 2 treatments: control and 3NOP (60 mg/kg of feed dry matter). Compared with the control, 3NOP decreased methane emission by 31% and increased hydrogen emission from undetectable to 1.33 g/d. Methane emissions per kilogram of dry matter intake and milk yield were also decreased 34% by 3NOP. Milk production and composition were not affected by 3NOP, except milk fat concentration was increased compared with the control. Concentrations of total VFA and propionate in ruminal fluid were not affected by treatment, but acetate concentration tended to be lower and acetate-to-propionate ratio was lower for 3NOP compared with the control. The 3NOP decreased the molar proportion of acetate and increase those of propionate, butyrate, valerate, and isovalerate. Deuterium-to-hydrogen ratios of methane and the abundance of (13)CH3D were similar between treatments. Compared with the control, minor (4‰) depletion in the (13)C/(12)C ratio was observed for 3NOP. Genus composition of methanogenic archaea (Methanobrevibacter, Methanosphaera, and Methanomicrobium) was not affected by 3NOP, but the proportion of methanogens in the total cell counts tended to be decreased by 3NOP. Prevotella spp., the predominant bacterial genus in ruminal contents in this experiment, was also not affected by 3NOP. Compared with the control, Ruminococcus and Clostridium spp. were decreased and Butyrivibrio spp. was increased by 3NOP. This experiment demonstrated that a substantial inhibition of enteric methane emission by 3NOP in dairy cows was accompanied with increased hydrogen emission and decreased acetate-to-propionate ratio; however, neither an effect on rumen archaeal community composition nor a significant change in the isotope composition of methane was observed.

Short communication: Comparison of the GreenFeed system with the sulfur hexafluoride tracer technique for measuring enteric methane emissions from dairy cows.

The objective of this study was to compare 2 commonly used techniques for measuring methane emissions from ruminant animals: the GreenFeed (GF) system and the sulfur hexafluoride (SF6) technique. The study was part of a larger experiment in which a methane inhibitor, 3-nitrooxypropanol, fed at 4 application rates (0, 40, 60, and 80 mg/kg of feed dry matter) decreased enteric methane emission by an average of 30% (measured by both GF and SF6) in a 12-wk experiment with 48 lactating Holstein cows fed a total mixed ration. The larger experiment used a randomized block design and was conducted in 2 phases (February to May, phase 1, and June to August, phase 2), with 2 sets of 24 cows in each phase. Using both GF and SF6 techniques, methane emission data were collected simultaneously during experimental wk 2, 6, and 12 (phase 1) and 2, 9, and 12 (phase 2), which corresponded to a total of 6 sampling periods. During each sampling period, 8 spot samples of gas emissions (staggered over a 3-d period) were collected from each cow using GF, as well as 3×24-h collections using the SF6 technique. Methane emission data were averaged per cow for the statistical analysis. The mean methane emission was 373 (standard deviation=96.3) and 405 (standard deviation=156) g/cow per day for GF and SF6, respectively. Coefficients of variation for the 2 methods were 25.8 and 38.6%, respectively; correlation and concordance between the 2 methods were 0.40 and 0.34, respectively. The difference in methane emission between the 2 methods (SF6 - GF) within treatment was from 46 to 144 and 24 to 27 g/d for phases 1 and 2, respectively. In the conditions of this experiment, the SF6 technique produced larger variability in methane emissions than the GF method. The overall difference between the 2 methods was on average about 8%, but was not consistent over time, likely influenced by barn ventilation and background methane and SF6 concentrations.

Topological Crystalline Insulator Phase in Graphene Multilayers.

While the experimental progress on three dimensional topological insulators is rapid, the development of their 2D counterparts has been comparatively slow, despite their technological promise. The main reason is materials challenges of the to date only realizations of 2D topological insulators, in semiconductor quantum wells. Here we identify a 2D topological insulator in a material which does not face similar challenges and which is by now most widely available and well charaterized: graphene. For certain commensurate interlayer twists, graphene multilayers are insulators with sizable band gaps. We show that they are moreover in a topological phase protected by crystal symmetry. As its fundamental signature, this topological state supports one-dimensional boundary modes. They form low-dissipation quantum wires that can be defined purely electrostatically.

Effects of 3-nitrooxypropanol on methane emission, digestion, and energy and nitrogen balance of lactating dairy cows.

The objective was to measure effects of 3-nitrooxypropanol (3 NP) on methane production of lactating dairy cows and any associated changes in digestion and energy and N metabolism. Six Holstein-Friesian dairy cows in mid-lactation were fed twice daily a total mixed ration with maize silage as the primary forage source. Cows received 1 of 3 treatments using an experimental design based on two 3 × 3 Latin squares with 5-wk periods. Treatments were a control placebo or 500 or 2,500 mg/d of 3 NP delivered directly into the rumen, via the rumen fistula, in equal doses before each feeding. Measurements of methane production and energy and N balance were obtained during wk 5 of each period using respiration calorimeters and digestion trials. Measurements of rumen pH (48 h) and postprandial volatile fatty acid and ammonia concentrations were made at the end of wk 4. Daily methane production was reduced by 3 NP, but the effects were not dose dependent (reductions of 6.6 and 9.8% for 500 and 2,500 mg/d, respectively). Dosing 3 NP had a transitory inhibitory effect on methane production, which may have been due to the product leaving the rumen in liquid outflow or through absorption or metabolism. Changes in rumen concentrations of volatile fatty acids indicated that the pattern of rumen fermentation was affected by both doses of the product, with a decrease in acetate:propionate ratio observed, but that acetate production was inhibited by the higher dose. Dry matter, organic matter, acid detergent fiber, N, and energy digestibility were reduced at the higher dose of the product. The decrease in digestible energy supply was not completely countered by the decrease in methane excretion such that metabolizable energy supply, metabolizable energy concentration of the diet, and net energy balance (milk plus tissue energy) were reduced by the highest dose of 3 NP. Similarly, the decrease in N digestibility at the higher dose of the product was associated with a decrease in body N balance that was not observed for the lower dose. Milk yield and milk fat concentration and fatty acid composition were not affected but milk protein concentration was greater for the higher dose of 3 NP. Twice-daily rumen dosing of 3 NP reduced methane production by lactating dairy cows, but the dose of 2,500 mg/d reduced rumen acetate concentration, diet digestibility, and energy supply. Further research is warranted to determine the optimal dose and delivery method of the product.

Effects of ethyl-3-nitrooxy propionate and 3-nitrooxypropanol on ruminal fermentation, microbial abundance, and methane emissions in sheep.

The aim of this work was to investigate the effect of feeding ethyl-3-nitrooxy propionate (E3NP) and 3-nitrooxypropanol (3 NP), 2 recently developed compounds with potential antimethanogenic activity, in vitro and in vivo in nonlactating sheep on ruminal methane production, fermentation pattern, the abundance of major microbial groups, and feed degradability. Three experiments were conducted, 1 in vitro and 2 in vivo. The in vitro batch culture trial (experiment 1) tested 2 doses of E3NP and 3 NP (40 and 80 µL/L), which showed a substantial reduction of methane production (up to 95%) without affecting concentration of volatile fatty acids (VFA). The 2 in vivo trials were conducted over 16 d (experiment 2) and 30 d (experiment 3) to study their effects in sheep. In experiment 2, 6 adult nonpregnant sheep, with permanent rumen cannula and fed alfalfa hay and oats (60:40), were treated with E3NP at 2 doses (50 and 500 mg/animal per day). After 7, 14, and 15 d of treatment, methane emissions were recorded in respiration chambers and rumen fluid samples were collected for VFA analysis and quantification of bacterial, protozoal, and archaeal numbers by real-time PCR. Methane production decreased by 29% compared with the control with the higher dose of E3NP on d 14 to 15. A decrease in the acetate:propionate ratio was observed without detrimental effects on dry matter intake. In experiment 3, 9 adult nonpregnant sheep, with permanent rumen cannula and fed with alfalfa hay and oats (60:40), were treated with E3NP or 3 NP at one dose (100mg/animal per day) over 30 d. On d 14 and d 29 to 30, methane emissions were recorded in respiration chambers. Rumen fluid samples were collected on d 29 and 30 for VFA analysis and quantification of bacterial, protozoal, and archaeal numbers by real-time PCR. In addition, on d 22 and 23, samples of oats and alfalfa hay were incubated in the rumen of sheep to determine dry matter ruminal degradation over 24 and 48 h, respectively; no effect was observed (78.6, 78.3, and 78.8% of alfalfa and 74.2, 74.0, and 70.6% of oats in control, E3NP, and 3 NP groups, respectively). A reduction in methane production was observed for both additives at d 14 and d 29 to 30. In both treatments, the acetate:propionate ratio was significantly decreased. Likewise, total concentrations of the analyzed microbial groups in the rumen showed no difference among treatments and doses for both experiments. Both tested compounds showed promise as methane inhibitors in the rumen, with no detrimental effects on fermentation or intake, which would need to be confirmed in lactating animals.

Scaling and interaction-assisted transport in graphene with one-dimensional defects.

We analyze the scattering from one-dimensional defects in intrinsic graphene. The Coulomb repulsion between electrons is found to be able to induce singularities of such scattering at zero temperature as in one-dimensional conductors. In striking contrast to electrons in one space dimension, however, repulsive interactions here can enhance transport. We present explicit calculations for the scattering from vector potentials that appear when strips of the material are under strain. There the predicted effects are exponentially large for strong scatterers.

Micrometeorological Methods for Measuring Methane Emission Reduction at Beef Cattle Feedlots: Evaluation of 3-Nitrooxypropanol Feed Additive.

It is highly desirable to test agricultural emission mitigation strategies in a whole-farm environment to ensure that all aspects of management and production operations are included. However, the large spatial scale of commercial operations makes the dual measurements of control and treatment(s) difficult. We evaluated the application of two micrometeorological methods, a novel concentration ratio method and an inverse dispersion method, where both were used to measure methane (CH) emission reductions in cattle fed the compound 3-nitrooxypropanol compared with cattle fed just the basal diet. In total, there were 1344 cattle used that were located in six pens (∼222 animals per pen). Three adjacent pens to the east and three to the west were designated as the treatment and control blocks, respectively. Underlying the emission reduction method was the assumption of site symmetry between the treatment and control pen blocks in the feedlot. There was, on average, a large CH emission reduction of ∼70% (±18%) due to the additive as found by both micrometeorological methods. Both methods also show a change in the diel distribution (peak emissions after initial morning feeding) and seasonal pattern (a decrease in emission reduction of 7.5 and 26.1% over 90 d). The simplicity of the developed concentration ratio method is expected to have applications for evaluating other mitigation strategies at large commercial scales (e.g., the application of manure additives to pens to reduce odors and ammonia emissions).

[His-bundle stimulation and alternative RV stimulation sites]. / HIS-Bündel-Stimulation und alternative rechtsventrikuläre Stimulationsorte.

The increasing evidence that right ventricular (RV) apical stimulation is detrimental for cardiac mechanics and increases the risk of new onset heart failure and mortality promotes strategies to avoid ventricular pacing and - if not applicable due to atrioventricular block - stipulates the search for alternative techniques of pacing the heart from the right ventricle. Despite more than 15 years of clinical research it remains unclear whether pacing from the right ventricular outflow tract or septum, dual site RV stimulation or selective pacing of the His bundle results in hemodynamic and prognostic benefit over the traditional method of apical RV pacing. The article reviews pertinent literature and tries to demonstrate pathophysiological mechanisms.

Rapid Communication: Evaluation of methane inhibitor 3-nitrooxypropanol and monensin in a high-grain diet using the rumen simulation technique (Rusitec).

The objective of this study was to evaluate the effects of 3-nitrooxypropanol (NOP), a known methane (CH) inhibitor; the ionophore monensin (MON); and their combination on in vitro CH production in a high-grain diet (85% barley grain, 10% barley silage, and 5% vitamin-mineral supplement; DM basis) using a rumen simulation technique (Rusitec). Sixteen fermentation vessels in 2 Rusitec apparatuses (blocks) were used in a completely randomized block design with 4 treatments: Control, NOP (200 µg/g DM), MON (200 µg/g DM), and the combination of 200 µg NOP/g DM and 200 µg MON/g DM (NOP + MON). Two fermenters within each apparatus were randomly assigned to a treatment. Treatments were mixed with 10 g of substrate and supplied on a daily basis. The study included an 8-d adaptation period without treatment supplementation and a 6-d period for addition of treatments. Dry matter disappearance, pH, and total VFA were not affected by treatment ( ≥ 0.34). Acetate proportion was decreased by 8.3% and 14.9% with NOP and NOP + MON ( < 0.01), respectively; however, propionate proportion was not affected by treatment ( = 0.44). The acetate to propionate ratio was lowered by 21.1% with the combination of NOP and MON ( = 0.02), whereas ammonia-N concentration was not affected by treatment ( = 0.50). Total gas production was unaffected ( = 0.50), but CH production decreased by 77.7% and 75.95% ( < 0.01) with NOP and NOP + MON addition, respectively. Concurrently, H gas production increased by 131.3% and 185.6% ( = 0.01) with NOP and NOP + MON treatments, respectively. The copy number of methanogens was decreased in both solid and liquid phases ( < 0.01) with NOP and NOP + MON treatments. Despite the combination of NOP + MON showing the greatest decrease in acetate molar proportion and acetate to propionate ratio, it did not further inhibit CH beyond the effect of NOP alone. The decrease in CH emissions with treatments that included NOP occurred along with a decrease in the copy number of methanogens associated with the solid and liquid phases, confirming the inhibitory effects of NOP on these microorganisms. In conclusion, the combined effects of NOP and MON on CH mitigation did not exceed the effect of NOP alone when using a high-grain diet in vitro.

[Clinical practice of dual antiplatelet therapy after percutaneous peripheral arterial interventions in Germany]. / Praxis der Thrombozyten-Aggregationshemmung nach Katheterintervention der Becken-/Beinarterien in Deutschland.

BACKGROUND AND AIM: Guideline recommendations regarding antithrombotic treatment with two antiplatelet agents (dual antiplatelet treatment) after peripheral interventional procedures are vague due to missing data from clinical trials. METHODS: 212 vascular centres in germany were evaluated regarding dual antiplatelet treatment using a standardized questionnaire with differentiation of localisation of the treated artery and interventional methods being used. RESULTS: 89 (42%) questionnaires returned completed. Application and duration of dual antiplatelet treatment after peripheral interventional procedures were quite different regarding interventional methods used (PTA: percutaneous transluminal angioplasty, DCB-PTA: drug coated ballon, Stenting, DES: drug eluting stent, Atherectomy). Mean duration of dual antiplatelet treatment were: PTA iliacal/femoro-popliteal 0 month, crural 1 month; DCB-Intervention and stenting: iliacal 1 month, femoro-popliteal 1,5 months, crural 2 months; DE-stenting iliacal 1,5 months, femoro-popliteal/crural 3 months and after femoro-popliteal / crural atherectomy 1 month. CONCLUSION: Data about dual antiplatelet treatment after peripheral interventional procedures are sparse.

Effects of sustained reduction of enteric methane emissions with dietary supplementation of 3-nitrooxypropanol on growth performance of growing and finishing beef cattle.

The study objective was to evaluate the effects of sustained reduction of enteric methane (CH) emissions with dietary supplementation of the inhibitor 3-nitrooxypropanol (NOP) on growth rate and feed conversion efficiency of growing and finishing beef cattle. Eighty-four crossbred steers were used in a 238-d feeding study and fed a backgrounding diet for the first 105 d (backgrounding phase) and transition diets for 28 d followed by a finishing diet for 105 d (finishing phase) with 3 doses of NOP (0, 100, and 200 mg/kg DM). The experiment was a completely randomized design using 21 pens (4 cattle/pen) with 7 pens per treatment. When cattle were fed the backgrounding diet, pen DMI was reduced ( < 0.01) whereas G:F tended to improve ( = 0.06) with increasing dose of NOP supplementation. During the finishing phase, DMI ( = 0.06) and ADG ( = 0.07) tended to decrease with increasing dose of NOP supplementation. Although both levels of NOP were effective in reducing CH emissions from the backgrounding diet ( < 0.01), only NOP supplemented at the highest dose was effective in reducing total CH emissions from the finishing diet ( < 0.01). Methane yield (g/kg DMI) was reduced whereas hydrogen emissions were increased at the highest dose of NOP supplementation with both backgrounding and finishing diets ( < 0.01). Overall, these results demonstrate efficacy of NOP in reducing enteric CH emissions from cattle fed backgrounding and finishing diets, and these effects were negated once NOP supplementation was discontinued.

IL-27 suppresses type 2 immune responses in vivo via direct effects on group 2 innate lymphoid cells.

Group 2 innate lymphoid cells (ILC2) were recently characterized by their ability to produce significant amounts of type-2 signature cytokines and drive central beneficial and pathological features of type-2 immune responses. Although factors such as IL-33 and IL-25 were shown to have ILC2 activating capacity, it is not well understood, how ILC2 responses are regulated in vivo. Here we provide compelling evidence that IL-27-signalling directly inhibits ILC2 responses and reveal a novel mechanism for negative regulation of the innate arm of type-2 immunity. We demonstrate that IL-27-deficiency is linked to increased mucosal presence of ILC2 in a model of inflammatory lung disease. Moreover, IL-27-treatment inhibited ILC2 proliferation and cytokine production and significantly reduced their accumulation in vivo. During helminth infection, regulation of ILC2 by IL-27 directly impacted anti-parasitic immunity. Thus, therapeutic modulation of the IL-27/IL-27R axis may be relevant in a number of inflammatory conditions associated with dysregulated type-2 responses.

Influence of right ventricular stimulation site on left ventricular function in atrial synchronous ventricular pacing.

OBJECTIVES: The study investigates the correlation between left ventricular function and QRS duration obtained by alternate right ventricular pacing sites. BACKGROUND: 1. Right ventricular apical pacing is associated with alterations of left ventricular contraction sequence. 2. A stimulation producing narrow QRS complexes is supposed to provide for better left ventricular contraction patterns. METHODS: Fourteen patients with third degree AV block received one ventricular pacing lead in apical position. The alternate lead was attached to that site on the septum that produced the smallest QRS complex as measured from the earliest to the last deflection in any of the orthogonal Frank leads (xyz). During atrial synchronous ventricular pacing, the AV delay was optimized individually and for each stimulation site using mitral valve doppler or impedance cardiography. By radionuclide ventriculography, the phase distribution histogram of left ventricular contraction was evaluated as area under the curve (AuC); systolic function was determined as ejection fraction (EF) and as absolute ejected counts (EC) in random order. The difference (delta) in QRS duration between apical and septal stimulation (deltaxyz) was correlated with the difference in phase distribution (deltaAuC) and ejection parameters (deltaEF, deltaEC). RESULTS: QRS duration was shorter with septal than with apical pacing in 9 out of 14 patients (64%); it was longer in 4 (29%), and no difference was seen in 1 patient. There was a significant positive correlation between the change in QRS duration (deltaxvz) and phase distribution (deltaAuC: r = 0.66393, p = 0.010) and a significant negative correlation to systolic function (deltaEF: r = 0.70931, p = 0.004; deltaEC: r = 0.74368, p = 0.002). CONCLUSIONS: In atrial synchronous right ventricular pacing, if the AV delay is adapted individually, decreased QRS duration obtained by alternate pacing sites is significantly correlated with homogenization of left ventricular contraction and with increased systolic function in acute tests.

Sustained reduction in methane production from long-term addition of 3-nitrooxypropanol to a beef cattle diet.

The objective was to evaluate whether long-term addition of 3-nitrooxypropanol (NOP) to a beef cattle diet results in a sustained reduction in enteric CH4 emissions in beef cattle. Eight ruminally cannulated heifers (637 ± 16.2 kg BW) were used in a completely randomized design with 2 treatments: Control (0 g/d of NOP) and NOP (2 g/d of NOP). Treatments were mixed by hand into the total mixed ration (60% forage, DM basis) at feeding time. Feed offered was restricted to 65% of ad libitum DMI (slightly over maintenance energy intake) and provided once per day. The duration of the experiment was 146 d, including an initial 18-d covariate period without NOP use; a 112-d treatment period with NOP addition to the diet, divided into four 28-d time intervals (d 1 to 28, 29 to 56, 57 to 84, and 85 to 112); and a final 16-d recovery period without NOP use. During the covariate period and at the end of each interval and the end of the recovery period, CH4 was measured for 3 d using whole animal metabolic chambers. The concentration of VFA was measured in rumen fluid samples collected 0, 3, and 6 h after feeding, and the microbial population was evaluated using rumen samples collected 3 h after feeding on d 12 of the covariate period, d 22 of each interval within the treatment period, and d 8 of the recovery period. Average DMI for the experiment was 7.04 ± 0.27 kg. Methane emissions were reduced by 59.2% when NOP was used (9.16 vs. 22.46 g/kg DMI; P < 0.01). Total VFA concentrations were not affected (P = 0.12); however, molar proportion of acetate was reduced and that for propionate increased when NOP was added (P < 0.01), which reduced the acetate to propionate ratio (3.0 vs. 4.0; P < 0.01). The total copy number of the 16S rRNA gene of total bacteria was not affected (P = 0.50) by NOP, but the copy number of the 16S rRNA gene of methanogens was reduced (P < 0.01) and the copy number of the 18S rRNA gene of protozoa was increased (P = 0.03). The residual effect of NOP for most of the variables studied was not observed or was minimal during the recovery period. These results demonstrated that the addition of NOP to a diet for beef cattle caused a sustained decrease of methanogenesis, with no sign of adaptation, and that these effects were reversed once NOP addition was discontinued

Comparison of aortic valve gradient during exercise after aortic valve reconstruction.

PURPOSE: Aortic valve preservation is a promising alternative to conventional composite replacement of aortic valve and ascending aorta. This approach may have a physiologic benefit compared with valve replacement similar to that seen in mitral valve reconstruction. We investigated aortic valve gradients at rest and during exercise in patients who had undergone valve-preserving aortic replacement and compared them with composite replacement of valve and aorta. METHODS: Four groups were studied: nine patients underwent composite valve replacement (group A: valve diameter, 23 to 27 mm), eight patients underwent remodeling of the aortic root (group B), and another nine patients had reimplantation of the aortic valve (group C). Healthy volunteers were studied as a control group (group D). Using continuous-wave Doppler echocardiography, all patients were examined on a bicycle ergometer for aortic valve gradients (0 to 75 W). RESULTS: There were no differences among the groups with respect to age, body surface, left ventricular end-diastolic diameter, fractional shortening, or left ventricular mass. Maximum resting gradients were significantly elevated in group A compared with groups B, C, and D (group A: 21.3 +/- 7.1 mm Hg; group B: 9.0 +/- 4.5 mm Hg; group C: 8.6 +/- 3.7 mm Hg; group D: 4.9 +/- 1.6 mm Hg; p < 0.05). At 75 W, group A exhibited significantly higher gradients than all other groups (group A: 31.3 +/- 7.5 mm Hg; group B: 13.9 +/- 6.6 mm Hg; group C: 12.8 +/- 3.5 mm Hg; group D: 9. 2 +/- 1.9 mm Hg; p < 0.05). There was no significant difference among the other groups. Both valve-preserving groups had only insignificantly higher gradients than the control group. CONCLUSION: Our data strongly support the suggestion that preserving the aortic valve restores nearly normal hemodynamic function of the aortic valve. Long-term observations will have to prove the clinical relevance of restoring physiologic aortic valve hemodynamics.

The potential of 3-nitrooxypropanol to lower enteric methane emissions from beef cattle.

This study evaluated if 3-nitrooxypropanol reduces enteric methane (CH4) emissions when added to the diet of beef cattle. The effects of 3-nitrooxypropanol on related variables including diet digestibility, ruminal fermentation, and ruminal microorganisms were also investigated. Eight ruminally cannulated Angus heifers (549 ± 64.3 kg [mean BW ± SD]) were fed a high forage diet (backgrounding diet) supplemented with 4 levels of 3-nitrooxypropanol (0, 0.75, 2.25 and 4.50 mg/kg BW). The experiment was designed as a duplicated 4 × 4 Latin square with 2 groups of heifers and four 28-d periods. Methane emissions were measured during 3 consecutive days using metabolic chambers. Up to a 5.8% reduction in ad libitum DMI was observed when 2.5 mg/kg BW of 3-nitrooxypropanol was fed (P = 0.03). Increasing level of 3-nitrooxypropanol linearly (P < 0.001) reduced CH4, with 33% less CH4 (corrected for DMI) at the highest level of supplementation compared with the control. Feed energy lost as CH4 was also reduced when 3-nitrooxypropanol was supplemented (P < 0.001). Molar proportion of acetate was reduced (P < 0.001) and that for propionate increased (P < 0.001) with increasing dose of 3-nitrooxypropanol, which in turn led to a reduction in the acetate to propionate ratio (P < 0.001). Total copy numbers of 16S ribosomal RNA (rRNA) genes for bacteria, methanogens, and 18S rRNA genes for protozoa in ruminal contents were not affected by 3-nitrooxypropanol supplementation (P ≥ 0.31). There was no effect of 3-nitrooxypropanol on DM (P = 0.1) digestibility in the total tract. The use of 4.5 mg/kg BW of 3-nitrooxypropanol in beef cattle consuming a backgrounding diet was effective in reducing enteric CH4 emissions without negatively affecting diet digestibility.