Effects of ensiling time on corn silage starch ruminal degradability evaluated in situ or in vitro.

Accurate measurements of concentration and ruminal degradability of corn silage starch is necessary for formulation of diets that meet the energy requirements of dairy cows. Five corn silage hybrids ensiled for 0 (unfermented), 30, 60, 120, and 150 d were used to determine the effects of ensiling time on starch degradability of corn silage. In addition, the effects of grind size of silage samples on 7-h in vitro starch degradability and the relationship between in vitro, in situ and near-infrared reflectance spectroscopy (NIRS) starch degradability were studied. In situ disappearance of corn silage starch increased from 0 to 150 d of ensiling, primarily as a result of an increase in the washout or rapidly degraded fraction of starch, particularly during the first 60 d of ensiling. When analyzed in vitro and by NIRS, ensiling time increased corn silage starch degradability either linearly or to a greater extent during the first 2 mo of ensiling. Differences in in situ starch disappearance among corn silage hybrids were apparent during the first 2 mo of ensiling but were attenuated as silages aged. No differences among hybrids were detected using a 7-h in vitro starch digestibility approach. Results from the in vitro subexperiment indicate that 7-h in vitro starch degradability was increased by reducing grind size of corn silage from 4 to 1 mm, regardless of ensiling duration. Fine grinding corn silages samples (i.e., 1-mm sieve) allowed distinguishing low- from medium- and high-starch degradability rated hybrids. Correlations among in situ, in vitro and NIRS measurements for starch degradability were medium to high (r ≥0.57); however, agreement among methods was low (concordance correlation coefficient ≤0.15). In conclusion, ensiling time linearly increased degradation rate of corn silage resulting in greater in situ starch disappearance after 150 d of ensiling. Reductions in grind size from 4 to 1 mm resulted in greater in vitro starch degradability, regardless of ensiling duration. Strong correlation but low agreement between starch degradability methods suggest that absolute estimations of corn silage starch degradability will vary, but all methods can be used to assess the effect of ensiling time on starch degradability.

Impact of obesity on morbidity and oncologic outcomes after total mesorectal excision for mid and low rectal cancer.

BACKGROUND: A recent meta-analysis showed that obesity increased the conversion rate and postoperative morbidity of rectal cancer surgery, but did not influence pathological results. However, this meta-analysis included patients with cancer of the upper rectum and had many biases. The aim of the present retrospective study was to investigate the impact of obesity, defined as a body mass index (BMI) ≥ 30 kg/m2, on postoperative morbidity and short- and long-term oncologic outcomes of total mesorectal excision for mid and low rectal cancer in consecutive patients. METHODS: This study included all eligible patients who were operated on for mid and lower rectal cancer between 1999 and 2018 in our hospital. We compared 90-day postoperative morbidity and mortality, and short- and long-term oncologic outcomes between obese and non-obese patients. RESULTS: Three hundred and ninety patients [280 males, mean age 65.7 ± 11.3 years, 59 obese individuals (15.1%)] were included. There was no difference in the 90-day mortality rate between obese and non-obese groups (p = 0.068). There was a difference in the overall 90-day morbidity rate between the obese and non-obese groups that disappeared after propensity score matching of the patients. There was no difference in short-term oncological parameters, with a median follow-up of 43 (20-84) months, and there were no significant differences in disease-free and overall survival between obese and non-obese patients (p = 0.42 and p = 0.11, respectively). CONCLUSIONS: Obesity does not affect the 90-day morbidity rate, or short- and long-term oncologic results in patients operated on for mid and lower rectal cancer.

Lactational performance, rumen fermentation, and enteric methane emission of dairy cows fed an amylase-enabled corn silage.

This study investigated the effects of an amylase-enabled corn silage on lactational performance, enteric CH4 emission, and rumen fermentation of lactating dairy cows. Following a 2-wk covariate period, 48 Holstein cows were blocked based on parity, days in milk, milk yield (MY), and CH4 emission. Cows were randomly assigned to 1 of 2 treatments in an 8-wk randomized complete block design experiment: (1) control corn silage (CON) from an isogenic corn without α-amylase trait and (2) Enogen hybrid corn (Syngenta Seeds LLC) harvested as silage (ECS) containing a bacterial transgene expressing α-amylase (i.e., amylase-enabled) in the endosperm of the grain. The ECS and CON silages were included at 40% of the dietary dry matter (DM) and contained, on average, 43.3 and 41.8% DM and (% DM) 36.7 and 37.5% neutral detergent fiber, and 36.1 and 33.1% starch, respectively. Rumen samples were collected from a subset of 10 cows using the ororuminal sampling technique on wk 3 of the experimental period. Enteric CH4 emission was measured using the GreenFeed system (C-Lock Inc.). Dry matter intake (DMI) was similar between treatments. Compared with CON, MY (38.8 vs. 40.8 kg/d), feed efficiency (1.47 vs. 1.55 kg of MY/kg of DMI), and milk true protein (1.20 vs. 1.25 kg/d) and lactose yields (1.89 vs. 2.00 kg/d) were increased, whereas milk urea nitrogen (14.0 vs. 12.7 mg/dL) was decreased, with the ECS diet. No effect of treatment on energy-corrected MY (ECM) was observed, but a trend was detected for increased ECM feed efficiency (1.45 vs. 1.50 kg of ECM/kg of DMI) for cows fed ECS compared with CON-fed cows. Daily CH4 emission was not affected by treatment, but emission intensity was decreased with the ECS diet (11.1 vs. 10.3 g/kg of milk, CON and ECS, respectively); CH4 emission intensity on ECM basis was not different between treatments. Rumen fermentation, apart from a reduced molar proportion of butyrate in ECS-fed cows, was not affected by treatment. Apparent total-tract digestibility of nutrients and urinary and fecal nitrogen excretions, apart from a trend for increased DM digestibility by ECS-fed cows, were not affected by treatment. Overall, ECS inclusion at 40% of dietary DM increased milk, milk protein, and lactose yields and feed efficiency, and tended to increase ECM feed efficiency but had no effect on ECM yield in dairy cows. The increased MY with ECS led to a decrease in enteric CH4 emission intensity, compared with the control silage.

Effects of ensiling time on corn silage neutral detergent fiber degradability and relationship between laboratory fiber analyses and in vivo digestibility.

Accurate analysis of degradability of silage neutral detergent fiber (NDF) is important for diet formulation and to predict lactational performance of dairy cows. In this study, 5 corn silage hybrids ensiled for 0 (unfermented), 30, 60, 120, and 150 d were used to determine the effects of ensiling time on silage neutral detergent fiber degradability (NDFD) and to assess the relationships between near-infrared reflectance spectroscopy (NIR) NDF-related analyses and in situ NDFD variables. In addition, the relationships between dietary concentration of indigestible NDF, 288-h incubation (iNDF288), or undegraded NDF, 240-h incubation (uNDF240), and in vivo total-tract apparent organic matter and NDF digestibility were studied in total mixed ration samples from 16 experiments with lactating dairy cows. Ensiling time had no effect on silage NDF concentration; however, the ratio of acid detergent fiber ÷ NDF increased, and estimated hemicellulose concentration decreased quadratically with ensiling time. Also, concentration of NDF-bound protein decreased, and that of lignin increased linearly with ensiling time. These changes in silage fiber composition resulted in a linear decrease in in situ effective degradability of silage NDF with increasing ensiling time. The indigestible fraction of NDF and concentration of structural carbohydrates were not affected by ensiling time. Correlations of in situ NDFD variables with laboratory NIR NDFD analyses were weak to moderate. The relationship of corn silage uNDF240 with lignin concentration or 30-h NDFD (all NIR analyses) was remarkably good (R2 = 0.73 and 0.88, respectively). The relationship between in situ iNDF288 concentration (but not uNDF240) and in vivo total-tract apparent digestibility of dietary organic matter and NDF was good (R2 = 0.72 and 0.80, respectively). In conclusion, in situ degradability of silage NDF linearly decreased from 0 to 150 d ensiling time, primarily caused by a decrease in concentrations of hemicellulose and NDF-bound protein. In situ NDF degradability measurements and common laboratory NIR NDF-related analyses were generally poorly correlated. We found a good relationship between in vivo NDF digestibility and dietary concentration of iNDF288 determined in situ, but the relationship with uNDF240 was poor.

Randomised controlled trial comparing preoperative carbohydrate loading with standard fasting in paediatric anaesthesia.

BACKGROUND: Preoperative fasting is a major cause of perioperative discomfort in paediatric anaesthesia and leads to postoperative insulin resistance, thus potentially enhancing the inflammatory response to surgery. Addressing these problems by preoperative carbohydrate intake has not been a well-defined approach in children. METHODS: We randomised 120 children scheduled for gastroscopy under general anaesthesia to either a control group of standard preoperative fasting or a study group receiving a carbohydrate beverage (PreOp™; Nutricia, Erlangen, Germany). Their stomach contents were aspirated endoscopically, and the volume and pH measured. Perioperative discomfort was evaluated using, among other parameters, an observational pain scale in ≤4-yr-olds and a VAS in >4-yr-olds. The investigators doing the endoscopies and outcome evaluations were blinded to the study group allocation. RESULTS: Compared with fasting, carbohydrate loading was associated with significantly less gastric content (P=0.01), fewer patients experiencing postoperative nausea (P=0.028), with no significant difference in postoperative vomiting. High preoperative VAS scores (>5) were recorded for only one child in the carbohydrate group vs five children in the fasting group. Bowel cleansing for simultaneous colonoscopies (n=61) made no difference to any of the intergroup findings. CONCLUSIONS: Preoperative carbohydrates can reduce nausea and gastric content, the latter being a surrogate parameter for the risk and severity of gastric aspiration into the lungs during anaesthesia. Our study adds knowledge for preoperative fasting guidelines in paediatric anaesthesia. CLINICAL TRIAL REGISTRATION: DRKS00005020.

Characterization of linoleic acid (C18:2) concentration in commercial corn silage and grain hybrids.

Corn silage and high-moisture corn grain are commonly recognized as risk factors for biohydrogenation-induced milk fat depression and may be due to the high concentration of linoleic acid (C18:2) in corn. Corn silage and corn grain have a low concentration of fatty acids (FA), but due to their high inclusion rate in diets they contribute substantially to unsaturated FA intake. The first objective of this study was to characterize the contribution of individual plant parts to total FA in whole-plant chopped corn. The second objective was to characterize the variation in FA profile in commercial silage and grain hybrids and evaluate the relationship between FA profile and other nutrients. To determine the location of FA in the corn plant, 4 stalks from 4 different commercial hybrids were separated into stalk, husk and shank, leaves, cob, and kernels. On a dry matter basis, 80.5% of total FA were in the kernels, 11.8% in the leaves, 5.1% in the stalk, 1.7% in the cob, and 1.0% in the husk and shank. More than 96% of the oleic acid (C18:1) and 92.5% of the C18:2 was in the kernels, whereas 71.0% of the linolenic acid (C18:3) was in the leaves. Next, the FA composition of fresh whole-plant chopped corn from 124 silage hybrids and grain from 72 grain hybrids was determined over 2 yr from test plots in Pennsylvania. Last, to extend the characterization, FA composition of whole-plant corn silage from 45 hybrids grown in test plots in South Dakota were characterized. In the fresh whole-plant chopped corn from PA test plots, C18:2 as a percentage of total FA averaged from 48.7% in 2013 (percentiles: 10th = 45.2, 90th = 52.2) and 48.0% in 2014 (percentiles: 10th = 44.1, 90th = 49.4). Concentration of C18:2 in corn grain averaged 57.5% in the 2013 (percentiles: 10th = 53.4, 90th = 60.8) and 56.1% in 2014 (percentiles: 10th = 53.5, 90th = 59.4). In the corn silage from South Dakota, the concentration of C18:2 as percentage of total FA averaged 45.4% (percentiles: 10th = 39.4, 90th = 50.2) and C18:2 concentration as a percent of dry matter averaged 1.1% (percentiles: 10th = 0.76, 90th = 1.41). An increase in the concentration of C18:2 was associated with a decrease in C18:3 in fresh whole-plant chopped corn and with a decrease in C18:1 in corn grain. Total FA and C18:2 (as a percentage of dry matter) were positively correlated with starch and negatively correlated with neutral detergent fiber in both fresh whole-plant chopped corn and corn silage samples, whereas no correlation with these traits was observed for C18:2 as a percentage of total FA. In conclusion, FA concentration and profile of corn silage reflects to a great extent the FA composition of kernels and the proportion of grain in the silage. The variation in C18:2 across hybrids provides the opportunity to develop selection programs to decrease C18:2 in corn silage and grain. Selection based on C18:2 concentration as a percent of total FA is preferred as this trait did not correlate with other nutritional properties.

Inclusion of brown midrib dwarf pearl millet silage in the diet of lactating dairy cows.

Brown midrib brachytic dwarf pearl millet (Pennisetum glaucum) forage harvested at the flag leaf visible stage and subsequently ensiled was investigated as a partial replacement of corn silage in the diet of high-producing dairy cows. Seventeen lactating Holstein cows were fed 2 diets in a crossover design experiment with 2 periods of 28 d each. Both diets had forage:concentrate ratios of 60:40. The control diet (CSD) was based on corn silage and alfalfa haylage, and in the treatment diet, 20% of the corn silage dry matter (corresponding to 10% of the dietary dry matter) was replaced with pearl millet silage (PMD). The effects of partial substitution of corn silage with pearl millet silage on dry matter intake, milk yield, milk components, fatty acid profile, apparent total-tract digestibility of nutrients, N utilization, and enteric methane emissions were analyzed. The pearl millet silage was higher in crude protein and neutral detergent fiber and lower in lignin and starch than the corn silage. Diet did not affect dry matter intake or energy-corrected milk yield, which averaged 46.7 ± 1.92 kg/d. The PMD treatment tended to increase milk fat concentration, had no effect on milk fat yield, and increased milk urea N. Concentrations and yields of milk protein and lactose were not affected by diet. Apparent total-tract digestibility of dry matter decreased from 66.5% in CSD to 64.5% in PMD. Similarly, organic matter and crude protein digestibility was decreased by PMD, whereas neutral- and acid-detergent fiber digestibility was increased. Total milk trans fatty acid concentration was decreased by PMD, with a particular decrease in trans-10 18:1. Urinary urea and fecal N excretion increased with PMD compared with CSD. Milk N efficiency decreased with PMD. Carbon dioxide emission was not different between the diets, but PMD increased enteric methane emission from 396 to 454 g/d and increased methane yield and intensity. Substituting corn silage with brown midrib dwarf pearl millet silage at 10% of the diet dry matter supported high milk production in dairy cows. When planning on farm forage production strategies, brown midrib dwarf pearl millet should be considered as a viable fiber source.

An integrated semiconductor device enabling non-optical genome sequencing.

The seminal importance of DNA sequencing to the life sciences, biotechnology and medicine has driven the search for more scalable and lower-cost solutions. Here we describe a DNA sequencing technology in which scalable, low-cost semiconductor manufacturing techniques are used to make an integrated circuit able to directly perform non-optical DNA sequencing of genomes. Sequence data are obtained by directly sensing the ions produced by template-directed DNA polymerase synthesis using all-natural nucleotides on this massively parallel semiconductor-sensing device or ion chip. The ion chip contains ion-sensitive, field-effect transistor-based sensors in perfect register with 1.2 million wells, which provide confinement and allow parallel, simultaneous detection of independent sequencing reactions. Use of the most widely used technology for constructing integrated circuits, the complementary metal-oxide semiconductor (CMOS) process, allows for low-cost, large-scale production and scaling of the device to higher densities and larger array sizes. We show the performance of the system by sequencing three bacterial genomes, its robustness and scalability by producing ion chips with up to 10 times as many sensors and sequencing a human genome.

Inclusion of wheat and triticale silage in the diet of lactating dairy cows.

The objective of this experiment was to partially replace corn silage with 2 alternative forages, wheat (Triticum aestivum) or triticale (X Triticosecale) silages at 10% of the diet dry matter (DM), and investigate the effects on dairy cow productivity, nutrient utilization, enteric CH4 emissions, and farm income over feed costs. Wheat and triticale were planted in the fall as cover crops and harvested in the spring at the boot stage. Neutral- and acid-detergent fiber and lignin concentrations were higher in the wheat and triticale silages compared with corn silage. The forages had similar ruminal in situ effective degradability of DM. Both alternative forages had 1% starch or less compared with the approximately 35% starch in corn silage. Diets with the alternative forages were fed in a replicated 3 × 3 Latin square design experiment with three 28-d periods and 12 Holstein cows. The control diet contained 44% (DM basis) corn silage. In the other 2 diets, wheat or triticale silages were included at 10% of dietary DM, replacing corn silage. Dry matter intake was not affected by diet, but both wheat and triticale silage decreased yield of milk (41.4 and 41.2 vs. 42.7 ± 5.18 kg/d) and milk components, compared with corn silage. Milk fat from cows fed the alternative forage diets contained higher concentrations of 4:0, 6:0, and 18:0 and tended to have lower concentrations of total trans fatty acids. Apparent total-tract digestibility of DM and organic matter was decreased in the wheat silage diet, and digestibility of neutral-and acid-detergent fiber was increased in the triticale silage diet. The wheat and triticale silage diets resulted in higher excretion of urinary urea, higher milk urea N, and lower milk N efficiency compared with the corn silage diet. Enteric CH4 emission per kilogram of energy-corrected milk was highest in the triticale silage diet, whereas CO2 emission was decreased by both wheat and triticale silage. This study showed that, at milk production of around 42 kg/d, wheat silage and triticale silage can partially replace corn silage DM and not affect DM intake, but milk yield may decrease slightly. For dairy farms in need of more forage, triticale or wheat double cropped with corn silage may be an appropriate cropping strategy.

Using brown midrib 6 dwarf forage sorghum silage and fall-grown oat silage in lactating dairy cow rations.

Double cropping and increasing crop diversity could improve dairy farm economic and environmental sustainability. In this experiment, corn silage was partially replaced with 2 alternative forages, brown midrib-6 brachytic dwarf forage sorghum (Sorghum bicolor) or fall-grown oat (Avena sativa) silage, in the diet of lactating dairy cows. We investigated the effect on dry matter (DM) intake, milk yield (MY), milk components and fatty acid profile, apparent total-tract nutrient digestibility, N utilization, enteric methane emissions, and income over feed cost. We analyzed the in situ DM and neutral detergent fiber disappearance of the alternative forages versus corn silage and alfalfa haylage. Sorghum was grown in the summer and harvested in the milk stage. Oats were grown in the fall and harvested in the boot stage. Compared with corn silage, neutral detergent fiber and acid detergent fiber concentrations were higher in the alternative forages. Lignin content was highest for sorghum silage and similar for corn silage and oat silage. The alternative forages had less than 1% starch compared with the approximately 35% starch in the corn silage. Ruminal in situ DM effective degradability was similar, although statistically different, for corn silage and oat silage, but lower for sorghum silage. Diets with the alternative forages were fed in a replicated 3 × 3 Latin square design experiment with three 28-d periods and 12 Holstein cows. The control diet contained 44% (DM basis) corn silage. In the other 2 diets, sorghum or oat silages were included at 10% of dietary DM, replacing corn silage. Sorghum silage inclusion decreased DM intake, MY, and milk protein content but increased milk fat and maintained energy-corrected MY similar to the control. Oat silage had no effect on DM intake, MY, or milk components compared to the control. The oat silage diet increased apparent total-tract digestibility of dietary nutrients, except starch, whereas the sorghum diet slightly decreased DM, organic matter, crude protein, and starch digestibility. Cows consuming the oat silage diet had higher milk urea N and urinary urea N concentrations. Milk N efficiency was decreased by the sorghum diet. Diet did not affect enteric methane or carbon dioxide emissions. This study shows that oat silage can partially replace corn silage at 10% of the diet DM with no effect on MY. Brown midrib sorghum silage harvested at the milk stage with <1% starch may decrease DM intake and MY in dairy cows.

The complete genome of an individual by massively parallel DNA sequencing.

The association of genetic variation with disease and drug response, and improvements in nucleic acid technologies, have given great optimism for the impact of 'genomic medicine'. However, the formidable size of the diploid human genome, approximately 6 gigabases, has prevented the routine application of sequencing methods to deciphering complete individual human genomes. To realize the full potential of genomics for human health, this limitation must be overcome. Here we report the DNA sequence of a diploid genome of a single individual, James D. Watson, sequenced to 7.4-fold redundancy in two months using massively parallel sequencing in picolitre-size reaction vessels. This sequence was completed in two months at approximately one-hundredth of the cost of traditional capillary electrophoresis methods. Comparison of the sequence to the reference genome led to the identification of 3.3 million single nucleotide polymorphisms, of which 10,654 cause amino-acid substitution within the coding sequence. In addition, we accurately identified small-scale (2-40,000 base pair (bp)) insertion and deletion polymorphism as well as copy number variation resulting in the large-scale gain and loss of chromosomal segments ranging from 26,000 to 1.5 million base pairs. Overall, these results agree well with recent results of sequencing of a single individual by traditional methods. However, in addition to being faster and significantly less expensive, this sequencing technology avoids the arbitrary loss of genomic sequences inherent in random shotgun sequencing by bacterial cloning because it amplifies DNA in a cell-free system. As a result, we further demonstrate the acquisition of novel human sequence, including novel genes not previously identified by traditional genomic sequencing. This is the first genome sequenced by next-generation technologies. Therefore it is a pilot for the future challenges of 'personalized genome sequencing'.

Molecular mechanisms involved in interleukin 1-beta (IL-1ß)-induced memory impairment. Modulation by alpha-melanocyte-stimulating hormone (α-MSH).

Pro-inflammatory cytokines can affect cognitive processes such as learning and memory. Particularly, interleukin-1ß (IL-1ß) influences the consolidation of hippocampus-dependent memories. We previously reported that administration of IL-1ß in dorsal hippocampus impaired contextual fear memory consolidation. Different mechanisms have been implicated in the action of IL-1ß on long-term potentiation (LTP), but the processes by which this inhibition occurs in vivo remain to be elucidated. We herein report that intrahippocampal injection of IL-1ß induced a significant increase in p38 phosphorylation after contextual fear conditioning. Also, treatment with SB203580, an inhibitor of p38, reversed impairment induced by IL-1ß on conditioned fear behavior, indicating that this MAPK would be involved in the effect of the cytokine. We also showed that IL-1ß administration produced a decrease in glutamate release from dorsal hippocampus synaptosomes and that treatment with SB203580 partially reversed this effect. Our results indicated that IL-1ß-induced impairment in memory consolidation could be mediated by a decrease in glutamate release. This hypothesis is sustained by the fact that treatment with d-cycloserine (DCS), a partial agonist of the NMDA receptor, reversed the effect of IL-1ß on contextual fear memory. Furthermore, we demonstrated that IL-1ß produced a temporal delay in ERK phosphorylation and that DCS administration reversed this effect. We also observed that intrahippocampal injection of IL-1ß decreased BDNF expression after contextual fear conditioning. We previously demonstrated that α-MSH reversed the detrimental effect of IL-1ß on memory consolidation. The present results demonstrate that α-MSH administration did not modify the decrease in glutamate release induced by IL-1ß. However, intrahippocampal injection of α-MSH prevented the effect on ERK phosphorylation and BDNF expression induced by IL-1ß after contextual fear conditioning. Therefore, in the present study we determine possible molecular mechanisms involved in the impairment induced by IL-1ß on fear memory consolidation. We also established how this effect could be modulated by α-MSH.

Bubble Jet agent release cartridge for chemical single cell stimulation.

We present a new method for the distinct specific chemical stimulation of single cells and small cell clusters within their natural environment. By single-drop release of chemical agents with droplets in size of typical cell diameters (d <30 µm) on-demand micro gradients can be generated for the specific manipulation of single cells. A single channel and a double channel agent release cartridge with integrated fluidic structures and integrated agent reservoirs are shown, tested, and compared in this publication. The single channel setup features a fluidic structure fabricated by anisotropic etching of silicon. To allow for simultaneous release of different agents even though maintaining the same device size, the second type comprises a double channel fluidic structure, fabricated by photolithographic patterning of TMMF. Dispensed droplet volumes are V = 15 pl and V = 10 pl for the silicon and the TMMF based setups, respectively. Utilizing the agent release cartridges, the application in biological assays was demonstrated by hormone-stimulated premature bud formation in Physcomitrella patens and the individual staining of one single L 929 cell within a confluent grown cell culture.

The effect of the molecular adsorbent recirculating system on moxifloxacin and meropenem plasma levels.

BACKGROUND: Adequate plasma antibiotic concentrations are necessary for effective elimination of invading microorganism; however, extracorporeal organ support systems are well known to alter plasma concentrations of antibiotics, requiring dose adjustments to achieve effective minimal inhibitory concentrations in the patient's blood. METHODS: A mock molecular adsorbent recirculating system (MARS) circuit was set using 5000 ml of bovine heparinized whole blood to simulate an 8-h MARS treatment session. After the loading dose of 400 mg of moxifloxacin or 2 g of meropenem had been added, blood was drawn from the different parts of the MARS circuit at various time points and analyzed by high-performance liquid chromatography. The experiments were performed in triplicate. Additionally, meropenem concentrations were determined in the plasma of one patient treated with MARS suffering from acute liver failure due to an idiosyncratic reaction to immunosuppressive medication. RESULTS: In our single-compartment model, a significant decrease in the quasi-systemic concentration of moxifloxacin and meropenem could be detected as early as 15 min after the commencing of the MARS circuit. Moreover, within 60 min the moxifloxacin and meropenem concentrations were less than 50% of the initial value. The activated charcoal removed the majority of moxifloxacin and meropenem in the albumin circuit. In our patient, the meropenem concentrations in the return line after MARS were constantly lower than in the access line, indicating a likely removal of meropenem through MARS. CONCLUSION: Our data provide evidence that moxifloxacin and meropenem are effectively removed from the patient's blood by MARS, leading to low plasma levels. Dose adjustments of both antibiotic compounds may be required.

[Does the resident care assessment instrument improve long-term home care? - results of a nation-wide study in Germany]. / Verbessert das Resident Assessment Instrument die ambulante Pflege? - Ergebnisse einer bundesweiten Studie.

BACKGROUND: Effective and efficient instruments for care planning and controlling are required to optimise the nursing process and improve outcome quality despite of various lacks of quality and precarious circumstances. METHODS: A cluster randomised controlled trial was conducted to assess whether the implementation of the Resident Assessment Instrument (RAI) into home care service providers can help to improve or stabilise functional abilities (ADL, IADL) and cognitive skills (MMST), improve quality of life (EQ-5D), reduce institutionalisation and thereby increase outcome quality. RESULTS: A comparison of mean differences between the treatment and control group showed no significant effects. Although the multilevel regression results show that clients in the treatment group fared better in terms of ADL and IADL (smaller decline) and were less likely to move to nursing homes and be hospitalised, none of these effects are significant. CONCLUSIONS: The lack of significance might be due to the fact that RAI was not fully implemented and even the partial implementation lasted much longer than expected. Moreover, the number of clients included in the study was smaller than originally planned.

Inhibition of acetyl-CoA carboxylase 2 enhances skeletal muscle fatty acid oxidation and improves whole-body glucose homeostasis in db/db mice.

AIMS/HYPOTHESIS: Excessive ectopic lipid deposition contributes to impaired insulin action in peripheral tissues and is considered an important link between obesity and type 2 diabetes mellitus. Acetyl-CoA carboxylase 2 (ACC2) is a key regulatory enzyme controlling skeletal muscle mitochondrial fatty acid oxidation; inhibition of ACC2 results in enhanced oxidation of lipids. Several mouse models lacking functional ACC2 have been reported in the literature. However, the phenotypes of the different models are inconclusive with respect to glucose homeostasis and protection from diet-induced obesity. METHODS: Here, we studied the effects of pharmacological inhibition of ACC2 using as a selective inhibitor the S enantiomer of compound 9c ([S]-9c). Selectivity was confirmed in biochemical assays using purified human ACC1 and ACC2. RESULTS: (S)-9c significantly increased fatty acid oxidation in isolated extensor digitorum longus muscle from different mouse models (EC(50) 226 nmol/l). Accordingly, short-term treatment of mice with (S)-9c decreased malonyl-CoA levels in skeletal muscle and concomitantly reduced intramyocellular lipid levels. Treatment of db/db mice for 70 days with (S)-9c (10 and 30 mg/kg, by oral gavage) resulted in improved oral glucose tolerance (AUC -36%, p < 0.05), enhanced skeletal muscle 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) uptake, as well as lowered prandial glucose (-31%, p < 0.01) and HbA(1c) (-0.7%, p < 0.05). Body weight, liver triacylglycerol, plasma insulin and pancreatic insulin content were unaffected by the treatment. CONCLUSIONS/INTERPRETATION: In conclusion, the ACC2-selective inhibitor (S)-9c revealed glucose-lowering effects in a mouse model of diabetes mellitus.

Serum 20S proteasome is elevated in patients with renal cell carcinoma and associated with poor prognosis.

BACKGROUND: To date, no reliable serum marker for clear cell renal cell carcinoma (CCRCC) is available. The aim of this study was to evaluate the putative significance of circulating 20S proteasome levels. METHODS: Preoperative 20S proteasome serum levels were determined in 113 CCRCC patients and 15 healthy controls by a sandwich enzyme-linked immunosorbent assay. Associations with CCRCC, pathological variables, disease-specific survival (DSS), and response to sunitinib were evaluated. RESULTS: Median 20S proteasome levels were higher in CCRCC patients than in healthy controls (4.66 vs 1.52 µg ml(-1), P<0.0001). The area under the receiver operating characteristics curve curve was 87.1%. The 20S proteasome levels were associated with symptoms (P=0.0008), distant metastases (P=0.0011), grade (P=0.0247), and necrosis (P=0.0462). The 20S proteasome levels were identified as a prognostic factor for DSS in both univariable (hazards ratio 1.21, P<0.001) and multivariable (hazards ratio 1.17, P=0.0015) survival analysis. In patients responding to sunitinib, 20S proteasome levels were lower than in patients with stable disease and progressive disease. CONCLUSION: This study demonstrates for the first time that increased 20S proteasome levels are associated with CCRCC, advanced disease, and poor prognosis. Routine use of this marker may allow better diagnosis, risk stratification, risk-adjusted follow-up, and identification of patients with a greater likelihood of response to targeted therapy.

Effect of preoperative fever-range whole-body hyperthermia on immunological markers in patients undergoing colorectal cancer surgery.

BACKGROUND: Previous studies have demonstrated beneficial immunological effects of fever-range whole-body hyperthermia (FR-WBH) as an adjunct to non-surgical cancer therapy. We conducted a study of preoperative FR-WBH in patients undergoing colorectal cancer surgery to evaluate perioperative, hyperthermia-induced immunomodulation. METHODS: The trial was conducted as a subject-blinded, controlled, randomized study. Subjects in the FR-WBH group (n=9) were treated with FR-WBH before operation under propofol sedation; the target core temperature was 39 (0.5)°C with 1 h warming and 2 h plateau phase. Subjects in the control group (n=9) were treated with propofol sedation only. Blood samples were acquired before and after treatment, after operation, and 24, 48 h, and 5 days after the end of surgery. The following parameters were measured: lipopolysaccharide (LPS)-induced tumour necrosis factor (TNF)-α, procalcitonin (PCT), interleukin (IL)-6/10, heat shock proteins (HSPs) 60, 70, and 90, human leucocyte antigen-DR (HLA-DR), and LPS-binding protein (LBP). RESULTS: HSPs were increased in the FR-WBH group after treatment [HSP60, 48 h postop: 143 (41)% vs 89 (42)%, P=0.04; HSP90, postop: 111 (33)% vs 64 (31)%, P=0.04; HSP70: P=0.40; FR-WBH vs control, P-values for area under the level/time curve]. TNF-α levels were elevated after surgery in the control group and remained near baseline in the FR-WBH group [24 h postop: 73 (68)% vs 151 (72)%, P=0.04]. PCT increased in both groups 24 h after surgery; in the control group, this increase was significantly higher (P=0.02). There were no significant differences for IL, HLA-DR, or LBP. CONCLUSIONS: The immune system to react to surgical stress, as measured by a panel of laboratory indicators, might be improved by preoperative FR-WBH.

Effects of the Resident Assessment Instrument in home care settings: results of a cluster randomized controlled trial.

Deficits in quality, a lack of professional process management and, most importantly, neglect of outcome quality are criticized in long-term care. A cluster randomized, controlled trial was conducted to assess whether the Resident Assessment Instrument (RAI) can help to improve or stabilize functional abilities (ADL, IADL) and cognitive skills (MMST), improve quality of life (EQ-5D), and reduce institutionalization, thereby, increasing outcome quality. A total of 69 home care services throughout Germany were included and randomized. The treatment group (n = 36) received training in RAI and was supported by the research team during the study (13 months). Comparison of mean differences between the treatment and control groups (n = 33) showed no significant effect. Although the multilevel regression results show that clients in the treatment group fared better in terms of ADLs and IADLs (smaller decline) and were less likely to move to nursing homes and be hospitalized, none of these effects is significant. The lack of significance might result from the small number of clients included in the study. Moreover, RAI was not fully implemented and even partial implementation required more time than expected.

Intra-operative rewarming with Hot Dog(®) resistive heating and forced-air heating: a trial of lower-body warming.

Resistive heating is an alternative to forced-air warming which is currently the most commonly used intra-operative warming system. We therefore tested the hypothesis that rewarming rates are similar with Hot Dog(®) (Augustine Biomedical) resistive and Bair Hugger(®) (Arizant) forced-air heating systems. We evaluated 28 patients having major maxillary tumour surgery. During the establishment of invasive monitoring, patients became hypothermic, dropping their core temperature to about 35 °C. They were then randomly assigned to rewarming with lower-body resistive (n = 14) or forced-air (n = 14) heating, with each system set to 'high'. Our primary outcome was the rewarming rate during active heating over a core temperature range from 35 to 37 °C. Morphometric characteristics were comparable in both groups. Temperature increased at twice the rate in patients assigned to forced-air warming, with an estimated mean (SE) slope of 0.49 (0.03) °C.h(-1) vs 0.24 (0.02) °C.h(-1) (p < 0.001). Resistive heating warmed at half the rate of forced air.