Test-retest reliability, construct validity and determinants of 6-minute walk test performance in adult patients with asthma.

INTRODUCTION AND OBJECTIVES: Current knowledge regarding the measurement properties of the 6-minute walk test (6MWT) in patients with asthma is limited. Therefore, the aim of this study was to assess the test-retest reliability, measurement error and construct validity of the 6MWT and identify determinants of 6-minute walk distance (6MWD) in patients with asthma. PATIENTS AND METHODS: 201 asthma patients referred for pre-pulmonary rehabilitation assessment, were retrospectively analyzed (age 61±12 years, 42% male, FEV1 78±27% predicted). Patients performed two 6MWTs on subsequent days using a 30 m straight walking course. Other measurements included resting dyspnea, maximal exercise capacity, body composition, pulmonary function, pulmonary and quadriceps muscle strength and symptoms of anxiety and depression. Measurement error (absolute reliability) was tested using standard error of measurement (SEM), minimal detectable change at 95% confidence interval (MDC95%) and Bland and Altman 95% limits of agreement, whereas test-retest reliability (relative reliability) and construct validity were assessed using the intra-class correlation coefficient (ICC2,1) and correlations, respectively. RESULTS: The 6MWD showed excellent test-retest reliability (ICC2,1: 0.91). The mean change in 6MWD after the second 6MWT was 18m (95%CI 11-24m), with 73% of the patients walking further in the second test. The SEM and MDC95% for the 6MWT were 35 m and 98 m, respectively. The best 6MWD correlated strongly with peak oxygen uptake during CPET and resting dyspnea (r = 0.61-0.64) and had no-to-moderate correlations with body composition, pulmonary function, respiratory and quadriceps muscle strength and symptoms of anxiety and depression (r = 0.02-0.45). Multiple linear regression was able to identify maximal workload, BMI, rollator use, maximal expiratory pressure, FEV1 and DLCO as independent determinants of the best 6MWD (R2 = 0.58). CONCLUSIONS: The 6MWT was considered to be reliable and valid in patients with asthma, which strengthens its clinical utility. However, the majority of patients demonstrated a considerable learning effect in the second 6MWT, providing a strong rationale for performing two 6MWTs.

Recruitment pattern of the diaphragm and extradiaphragmatic inspiratory muscles in response to different levels of pressure support.

BACKGROUND: Inappropriate ventilator assist plays an important role in the development of diaphragm dysfunction. Ventilator under-assist may lead to muscle injury, while over-assist may result in muscle atrophy. This provides a good rationale to monitor respiratory drive in ventilated patients. Respiratory drive can be monitored by a nasogastric catheter, either with esophageal balloon to determine muscular pressure (gold standard) or with electrodes to measure electrical activity of the diaphragm. A disadvantage is that both techniques are invasive. Therefore, it is interesting to investigate the role of surrogate markers for respiratory dive, such as extradiaphragmatic inspiratory muscle activity. The aim of the current study was to investigate the effect of different inspiratory support levels on the recruitment pattern of extradiaphragmatic inspiratory muscles with respect to the diaphragm and to evaluate agreement between activity of extradiaphragmatic inspiratory muscles and the diaphragm. METHODS: Activity from the alae nasi, genioglossus, scalene, sternocleidomastoid and parasternal intercostals was recorded using surface electrodes. Electrical activity of the diaphragm was measured using a multi-electrode nasogastric catheter. Pressure support (PS) levels were reduced from 15 to 3 cmH2O every 5 min with steps of 3 cmH2O. The magnitude and timing of respiratory muscle activity were assessed. RESULTS: We included 17 ventilated patients. Diaphragm and extradiaphragmatic inspiratory muscle activity increased in response to lower PS levels (36 ± 6% increase for the diaphragm, 30 ± 6% parasternal intercostals, 41 ± 6% scalene, 40 ± 8% sternocleidomastoid, 43 ± 6% alae nasi and 30 ± 6% genioglossus). Changes in diaphragm activity correlated best with changes in alae nasi activity (r2 = 0.49; P < 0.001), while there was no correlation between diaphragm and sternocleidomastoid activity. The agreement between diaphragm and extradiaphragmatic inspiratory muscle activity was low due to a high individual variability. Onset of alae nasi activity preceded the onset of all other muscles. CONCLUSIONS: Extradiaphragmatic inspiratory muscle activity increases in response to lower inspiratory support levels. However, there is a poor correlation and agreement with the change in diaphragm activity, limiting the use of surface electromyography (EMG) recordings of extradiaphragmatic inspiratory muscles as a surrogate for electrical activity of the diaphragm.

Dietary fibre enrichment of supplemental feed modulates the development of the intestinal tract in suckling piglets.

BACKGROUND: Commercial pre-weaning diets are formulated to be highly digestible and nutrient-dense and contain low levels of dietary fibre. In contrast, pigs in a natural setting are manipulating fibre-rich plant material from a young age. Moreover, dietary fibre affects gastrointestinal tract (GIT) development and health in older pigs. We hypothesised that supplemental diets that contain vegetal fibres are accelerating GIT development in suckling piglets in terms of size and functionality. From d 2 of life, sow-suckled piglets had access to a low fibre diet (CON), a diet with a fermentable long-chain arabinoxylan (lc-AXOS), a diet with a largely non-fermentable purified cellulose (CELL), or a diet containing both fibres. During the initial 2 weeks, the control diet was a high-density milk replacer, followed by a dry and highly digestible creep meal. Upon weaning at 25 d, 15 piglets from each treatment group, identified as eaters and originating from six or seven litters, were sacrificed for post-mortem examination of GIT morphology, small intestinal permeability and metabolic profile of the digesta. The microbiota composition of the mid-colon was evaluated in a sub-set of ten piglets. RESULTS: No major statistical interactions between the fibre sources were observed. Piglets consumed the fibre-containing milk supplements and creep diets well. Stomach size and small intestinal permeability was not affected. Large intestinal fill was increased with lc-AXOS only, while relative large intestinal weight was increased with both fibre sources (P < 0.050). Also, CELL decreased ileal pH and tended to increase ileal DM content compared to CON (P < 0.050). Moreover, the concentration of volatile fatty acids was increased in the caecum (P < 0.100) and mid-colon (P < 0.050) by addition of CELL. lc-AXOS only stimulated caecal propionate (P < 0.050). The microbiota composition showed a high individual variation and limited dietary impact. Nonetheless, CELL induced minor shifts in specific genera, with notable reductions of Escherichia-Shigella. CONCLUSIONS: Adding dietary fibres to the supplemental diet of suckling piglets altered large intestinal morphology but not small intestinal permeability. Moreover, dietary fibre showed effects on fermentation and modest changes of microbial populations in the hindgut, with more prominent effects from the low-fermentable cellulose.

The effect of metabolic alkalosis on the ventilatory response in healthy subjects.

BACKGROUND: Patients with acute respiratory failure may develop respiratory acidosis. Metabolic compensation by bicarbonate production or retention results in posthypercapnic alkalosis with an increased arterial bicarbonate concentration. The hypothesis of this study was that elevated plasma bicarbonate levels decrease respiratory drive and minute ventilation. METHODS: In an intervention study in 10 healthy subjects the ventilatory response using a hypercapnic ventilatory response (HCVR) test was assessed, before and after administration of high dose sodium bicarbonate. Total dose of sodiumbicarbonate was 1000 ml 8.4% in 3 days. RESULTS: Plasma bicarbonate increased from 25.2 ±â€¯2.2 to 29.2 ±â€¯1.9 mmol/L. With increasing inspiratory CO2 pressure during the HCVR test, RR, Vt, Pdi, EAdi and VE increased. The clinical ratio ΔVE/ΔPetCO2 remained unchanged, but Pdi, EAdi and VE were significantly lower after bicarbonate administration for similar levels of inspired CO2. CONCLUSION: This study demonstrates that in healthy subjects metabolic alkalosis decreases the neural respiratory drive and minute ventilation, as a response to inspiratory CO2.

Short communication: insoluble fibres in supplemental pre-weaning diets affect behaviour of suckling piglets.

We investigated the effect of offering supplementary dietary fibres to suckling piglets on their behaviour and performance before weaning. From 5 to 22 days of age, suckling piglets were offered a high-fibre diet (HF; 5% cellulose; n=5 litters), or a control low-fibre diet (n=5 litters). Piglets were housed with the sows in individual farrowing pens, and had access to maternal milk until weaning, at 23 days of age. Behaviours of six focal piglets per pen were scored at 6, 16 and 21 days of age. All piglets were individually weighed at 5, 15 and 20 days of age and feed intake was measured daily at the pen level. Piglets on the HF diet were more active than controls (P=0.05), and spent more time suckling or massaging the udder (P=0.01) and interacting with pen mates (P=0.008). Time spent manipulating pen mates, which may reflect re-directed foraging activity in the absence of substrate, accounted for most of the time spent interacting with pen mates (⩾73% of total time spent interacting). Dietary fibres had no effect on BW and feed intake. In conclusion, inclusion of cellulose in the supplemental diet of suckling piglets affects behaviour, with no deleterious effects on performance before weaning.

Development of a Salmonella Typhimurium challenge model in weaned pigs to evaluate effects of water and feed interventions on fecal shedding and growth performance.

The aim of this study was to develop a Typhimurium (ST) challenge model in weaned pigs suitable to evaluate effects of water and feed interventions on fecal shedding and growth performance. Two studies were performed. In Exp. 1 weaned pigs were fed either a standard diet (CON) or a diet with a high buffer capacity (HB) and challenged for either 3 or 7 consecutive days in a Latin square design with 4 × 8 individually housed pigs. In Exp. 2, the CON 7-d challenge method was chosen for further model development and validation. Thirty-two individually housed weaned pigs were divided over 4 treatments: a nonchallenged control group (NCON), a challenged positive control group (PCON), a challenged intervention group with acidified water (WATER), and a challenged intervention group with acidified feed (FEED). Pigs were orally challenged once daily on d 7 to 9 or d 7 to 13 after weaning (d 0) with 1 ×10 cfu ST. From d 0 to 28, rectal temperature and occurrence of diarrhea were recorded daily, and BW and feed intake were measured weekly. Fecal samples were collected on d 0, 2, 7, 9, 13, 16, 20, 23, and 27 in Exp. 1 and d 0, 2, 7, 8, 9, 13, 15, and 27 in Exp. 2 for quantification. The results of both experiments showed quantifiable fecal shedding (average peak shedding of approximately 3.5 log and 5.5 log cfu/g, respectively), accompanied by a transient 0.5°C increase in rectal temperature and an increase in occurrence of diarrhea. In Exp. 2 during the week of challenge (i.e., d 7 to 14), a reduction in growth performance (ADG: -157 to 200 g/d and G:F: -0.22 to 0.25 g/d; < 0.01) in PCON and FEED was observed compared to NCON, with WATER showing an intermediate response. The WATER treatment also showed a numerically lower peak shedding (difference of -1.3 to 1.4 log cfu/g) compared to PCON and FEED. To conclude, we repeatedly infected weaned pigs successfully with 1 × 10 cfu of ST for 7 consecutive days, resulting in detectable and quantifiable fecal shedding. This ST challenge model may be suitable for evaluation of effects of water and feed interventions on peak fecal shedding and growth performance.

Heavy-flavour and quarkonium production in the LHC era: from proton-proton to heavy-ion collisions.

This report reviews the study of open heavy-flavour and quarkonium production in high-energy hadronic collisions, as tools to investigate fundamental aspects of Quantum Chromodynamics, from the proton and nucleus structure at high energy to deconfinement and the properties of the Quark-Gluon Plasma. Emphasis is given to the lessons learnt from LHC Run 1 results, which are reviewed in a global picture with the results from SPS and RHIC at lower energies, as well as to the questions to be addressed in the future. The report covers heavy flavour and quarkonium production in proton-proton, proton-nucleus and nucleus-nucleus collisions. This includes discussion of the effects of hot and cold strongly interacting matter, quarkonium photoproduction in nucleus-nucleus collisions and perspectives on the study of heavy flavour and quarkonium with upgrades of existing experiments and new experiments. The report results from the activity of the SaporeGravis network of the I3 Hadron Physics programme of the European Union 7[Formula: see text] Framework Programme.

Supplementation of piglets with nutrient-dense complex milk replacer improves intestinal development and microbial fermentation.

Weaning of piglets causes stress due to environmental, behavioral, and nutritional stressors and can lead to postweaning diarrhea and impaired gut development. The diet changes experienced during weaning require extensive adaptation of the digestive system. A well-developed piglet that had creep-feed experience before weaning performs better after weaning. In the current study, the effect of providing sow-fed piglets with a supplemental nutrient-dense complex milk replacer (NDM) on gut development and growth performance was studied. Litters of sows with similar parities (3.6 ± 0.8) and similar numbers of live born piglets (13.5 ± 0.3) were assigned to 1 of 2 groups: 1 group of piglets had ad libitum access to NDM from Day 2 through 21 after birth, whereas the other group was used as controls. Nutrient-dense complex milk replacer-fed piglets were shown to be significantly heavier after 21 d of supplementation compared with the control piglets. At Day 21, 3 piglets from each litter were euthanized for morphological and functional analyses of the intestinal tract. The small intestines of NDM-fed piglets had significantly higher weights (g) as well as significantly higher relative weight:length ratios (g//cm) compared with the small intestines of control piglets ( < 0.05). Morphometric analysis demonstrated that villi length and numbers of goblet cells did not differ between groups. However, NDM-fed piglets had deeper crypts ( < 0.001) and an increased expression of the cell-proliferation marker proliferating cell nuclear antigen in crypts ( < 0.05), suggesting higher cell-proliferation rates. The gene encoding IGF-1 showed a tendency to higher gene expression in the jejunum from NDM-fed piglets ( = 0.07) compared with the jejunum from control piglets, suggesting that IGF-1 might be involved in the regulation of cell proliferation and intestinal growth. Finally, as a result of dietary fiber in NDM, piglets showed significantly increased concentrations of metabolic fermentation products. This suggests differences in metabolic activity in the colon between treatment groups. In conclusion, providing sow-fed piglets with NDM before weaning stimulates intestinal proliferation, leading to increased circular growth. Nutrient-dense complex milk replacer supplementation might, therefore, help piglets through the transition period at weaning by increased BW and increased capacity for uptake of nutrients.

Relative prolactin-to-progesterone concentrations around farrowing influence colostrum yield in primiparous sows.

In swine, colostrum production is induced by the drop of progesterone (P4) concentrations which leads to the prepartum peak of prolactin (PRL). PRL regulates mammary cell turnover and stimulates lacteal nutrient synthesis. P4 inhibits PRL secretion and downregulates the PRL receptor in the mammary gland. The aim of the present study was to determine if the relative prepartum concentrations of P4 and PRL (PRL/P4 ratio) influence sow colostrum production. The performance of 29 Landrace × Large White primiparous sows was analyzed. Colostrum yield was estimated during 24 h starting at the onset of parturition (T0) using litter weight gains. Colostrum was collected at T0 and 24 h later (T24). Repeated jugular blood samples were collected during the peripartum period, that is, from -72 to +24 h related to farrowing and were assayed for P4 and PRL. Sows were retrospectively categorized in 2 groups according to their PRL/P4 ratio 24 h before farrowing being either <2 (low PRL/P4, n = 16) or >3 (high PRL/P4, n = 13). During the peripartum period, the circulating concentrations of P4 were lower (P < 0.05) and those of PRL tended to be greater (P < 0.10) in high PRL/P4 compared with low PRL/P4 sows. Colostrum yield was greater in high PRL/P4 compared with low PRL/P4 sows (4.11 vs 3.48 kg [root mean square error = 0.69], P < 0.05). Colostrum composition (dry matter, energy, protein, lipid, and lactose contents) and IgG and IgA concentrations did not differ between the 2 groups of sows (P > 0.10). The Na/K ratio in colostrum 24 h after the onset of farrowing was lower in high PRL/P4 compared with low PRL/P4 sows (P < 0.05). Piglet mortality between birth and T24 averaged 10.0% in low PRL/P4 litters and 7.0% in high PRL/P4 litters (P = 0.29). In conclusion, a greater PRL/P4 ratio 24 h prepartum, characterized by lower P4 concentrations and a trend for greater PRL concentrations peripartum, led to increased colostrum yield in primiparous sows.

Effects of alginate and resistant starch on feeding patterns, behaviour and performance in ad libitum-fed growing pigs.

This study assessed the long-term effects of feeding diets containing either a gelling fibre (alginate (ALG)), or a fermentable fibre (resistant starch (RS)), or both, on feeding patterns, behaviour and growth performance of growing pigs fed ad libitum for 12 weeks. The experiment was set up as a 2×2 factorial arrangement: inclusion of ALG (yes or no) and inclusion of RS (yes or no) in the control diet, resulting in four dietary treatments, that is, ALG-RS- (control), ALG+RS-, ALG-RS+, and ALG+RS+. Both ALG and RS were exchanged for pregelatinized potato starch. A total of 240 pigs in 40 pens were used. From all visits to an electronic feeding station, feed intake and detailed feeding patterns were calculated. Apparent total tract digestibility of energy, dry matter (DM), and CP was determined in week 6. Pigs' postures and behaviours were scored from live observations in weeks 7 and 12. Dietary treatments did not affect final BW and average daily gain (ADG). ALG reduced energy and DM digestibility (P<0.01). Moreover, ALG increased average daily DM intake, and reduced backfat thickness and carcass gain : digestible energy (DE) intake (P<0.05). RS increased feed intake per meal, meal duration (P<0.05) and inter-meal intervals (P=0.05), and reduced the number of meals per day (P<0.01), but did not affect daily DM intake. Moreover, RS reduced energy, DM and CP digestibility (P<0.01). Average daily DE intake was reduced (P<0.05), and gain : DE intake tended to be increased (P=0.07), whereas carcass gain : DE intake was not affected by RS. In week 12, ALG+RS- increased standing and walking, aggressive, feeder-directed, and drinking behaviours compared with ALG+RS+ (ALG×RS interaction, P<0.05), with ALG-RS- and ALG-RS+ in between. No other ALG×RS interactions were found. In conclusion, pigs fed ALG compensated for the reduced dietary DE content by increasing their feed intake, achieving similar DE intake and ADG as control pigs. Backfat thickness and carcass efficiency were reduced in pigs fed ALG, which also showed increased physical activity. Pigs fed RS changed feeding patterns, but did not increase their feed intake. Despite a lower DE intake, pigs fed RS achieved similar ADG as control pigs by increasing efficiency in DE use. This indicates that the energy utilization of RS in pigs with ad libitum access to feed is close to that of enzymatically digestible starch.

Identifying the limitations for growth in low performing piglets from birth until 10 weeks of age.

The evolution of hyper-prolific pig breeds has led to a higher within-litter variation in birth weight and in BW gain during the nursery phase. Based on an algorithm developed in previous research, two populations from a pool of 368 clinically healthy piglets at 6 weeks of age were selected: a low (LP) and a high (HP) performing population and their development was monitored until the end of the nursery phase (10 weeks of age). To understand the cause of the variation in growth between these populations we characterized the LP and HP piglets in terms of body morphology, behaviour, voluntary feed intake, BW gain, and apparent total tract and ileal nutrient digestibility. Piglets were housed individually and were fed a highly digestible diet. At selection, 6 weeks of age, the BW of LP and HP piglets were 6.8±0.1 and 12.2±0.1 kg, respectively. Compared with the LP piglets the HP piglets grew faster (203 g/day), ate more (275 g/day) from 6 to 10 weeks of age and were heavier at 10 weeks (30.0 v. 18.8 kg, all P<0.01). Yet, the differences in average daily gain and average daily feed intake disappeared when compared per kg BW0.75. Assuming similar maintenance requirements per kg BW0.75 the efficiency of feed utilization above maintenance was 0.1 g/g lower for the LP piglets (P=0.09).The gain : feed ratio was similar for both groups. LP piglets tended to take more time to touch a novel object (P=0.10), and spent more time eating (P<0.05). At 10 weeks, LP piglets had a higher body length and head circumference relative to BW (P<0.01). Relative to BW, LP had a 21% higher small intestine weight; 36% longer length, and relative to average FI, the small intestinal weight was 4 g/kg higher (both P=<0.01). Apparent total tract and ileal dry matter, N and gross energy digestibility were similar between groups (P>0.10). We concluded that the low performance of the LP piglets was due to their inability to engage compensatory gain or compensatory feed intake as efficiency of nutrient utilization and feed intake per kg BW0.75 was unaffected. LP piglets tend to be more fearful towards novel objects. The morphological comparisons, increased body length and head circumference relative to BW imply that LP piglets have an increased priority for skeletal growth.

Resveratrol attenuates NF-κB-binding activity but not cytokine production in mechanically ventilated mice.

BACKGROUND: Mechanical ventilation (MV) can result in inflammation and subsequent lung injury. Toll-like receptor (TLR)4 and NF-κB are proposed to play a crucial role in the MV-induced inflammatory response. Resveratrol (RVT) exhibits anti-inflammatory effects in vitro and in vivo supposedly by interfering with TLR4 signaling and NF-κB. In the present study, we investigated the role of RVT in MV-induced inflammation in mice. METHODS: RVT (10 mg/kg, 20 mg/kg and 40 mg/kg) or vehicle was intraperitoneally administered 1 h before start of MV (4 h, tidal volume 8 ml/kg, positive end-expiratory pressure 1,5 cmH2 O and FiO2 0.4). Blood and lungs were harvested for cytokine analysis. DNA binding activity of transcription factor NF-κB was measured in lung homogenates. RESULTS: MV resulted in elevated pulmonary concentrations of IL-1ß, IL-6, keratinocyte-derived chemokine (KC) and NF-κB DNA-binding activity. RVT at 10, 20 and 40 mg/kg reduced NF-κB's DNA-binding activity following MV compared with ventilated controls. However, no differences in cytokine release were found between RVT-treated and control ventilated mice. Similarly, in plasma, MV resulted in elevated concentrations of TNF-α, KC and IL-6, but RVT did not affect cytokine levels. CONCLUSIONS: RVT abrogates the MV-induced increase in pulmonary NF-κB activity but does not attenuate cytokine levels. This implies a less prominent role for NF-κB in MV-induced inflammation than previously assumed.

Non-invasive ventilation abolishes the IL-6 response to exercise in muscle-wasted COPD patients: a pilot study.

Systemic inflammation in patients with chronic obstructive pulmonary disease (COPD) has been related to the development of comorbidities. The level of systemic inflammatory mediators is aggravated as a response to exercise in these patients. The aim of this study was to investigate whether unloading of the respiratory muscles attenuates the inflammatory response to exercise in COPD patients. In a cross-over design, eight muscle-wasted stable COPD patients performed 40 W constant work-rate cycle exercise with and without non-invasive ventilation support (NIV vs control). Patients exercised until symptom limitation for maximally 20 min. Blood samples were taken at rest and at isotime or immediately after exercise. Duration of control and NIV-supported exercise was similar, both 12.9 ± 2.8 min. Interleukin- 6 (IL-6) plasma levels increased significantly by 25 ± 9% in response to control exercise, but not in response to NIV-supported exercise. Leukocyte concentrations increased similarly after control and NIV-supported exercise by ∼15%. Plasma concentrations of C-reactive protein, carbonylated proteins, and production of reactive oxygen species by blood cells were not affected by both exercise modes. This study demonstrates that NIV abolishes the IL-6 response to exercise in muscle-wasted patients with COPD. These data suggest that the respiratory muscles contribute to exercise-induced IL-6 release in these patients.

Predicted high-performing piglets exhibit more and larger skeletal muscle fibers.

Postnatal (muscle) growth potential in pigs depends on the total number and hypertrophy of myofibers in skeletal muscle tissue. In a previous study an algorithm was developed to predict piglet BW at the end of the nursery period (10 wk of age) on the basis of BW at birth, at weaning, and at 6 wk of age. The objective of this study was to determine whether the differences in growth performance between poor (PP) and high (HP) performing piglets could be the result of different skeletal muscle properties. Therefore, from a total of 368 piglets (offspring from Hypor sows bred to TOPIGS sires) 2 groups with a divergent growth performance were selected at 6 wk of age: HP (n = 20, predicted BW at 10 wk of age 26.8-30.9 kg) and PP (n = 20, predicted BW at 10 wk of age 16.0-22.9 kg). Piglets were euthanized at 10 wk of age, and samples of the semitendinosus muscle (STN) were collected for histochemistry and gene expression analysis using quantitative PCR (qPCR). At 10 wk of age, realized BW did not differ from predicted BW in either group (P > 0.880). The HP piglets exhibited greater ADG and ADFI from 6 to 10 wk and greater BW at birth and 6 and 10 wk of age (P ≤ 0.002) compared with the PP piglets, whereas G:F ratio was similar (P = 0.417). Superior growth performance of HP piglets was associated with a 1.27-fold higher IGF1 plasma concentration at 10 wk compared with the PP piglets (P = 0.044). The greater weight and muscle cross-sectional area of STN in HP piglets was due to a 1.20-fold increase in total muscle fiber number (TFN; P = 0.009) and 1.34-fold increase in fiber cross-sectional area (FCSA; P = 0.004) compared with the PP piglets. The number of myonuclei per red and intermediate fiber was greater in HP piglets (P ≤ 0.097), but the nucleus-to-cytoplasm ratio was unaffected by the performance group (P = 0.861). The mRNA expression of proliferating cell nuclear antigen (PCNA), paired box 7 (PAX7), myogenic factor 5 (MYF5), and myogenic differentiation factor (MYOD) did not differ between groups (P ≥ 0.327). However, IGF2-specific mRNA expression was numerically higher in the HP piglets (P = 0.101). The greater myofiber number, the higher degree of myofiber hypertrophy, and the increased muscular mRNA expression of IGF2 indicate that HP piglets exhibit a greater capacity for lean accretion and may grow faster until market weight. In summary, pigs that were selected for predicted high BW at 10 wk of age using a complex selection model had a superior muscularity in terms of greater TFN and FCSA, which may be of advantage for lean mass accretion in later life and for meat quality.

Analysis of factors to predict piglet body weight at the end of the nursery phase.

In pig (Sus Scrofa) production, within-batch variation in bw gain of piglets during the nursery period (up to 10 wk of age) can be high and is of high economic importance. Homogeneity of BW within batches of animals is important as it influences the efficiency of use of the grower and finisher facilities, and provides an extra value for the fattening farms. In the current study, factors for a light BW at the end of the nursery period of pigs were determined by analyzing datasets from 3 different swine research centers in the Netherlands and France. The entire dataset contained information on 77,868 individual piglets born between 2005 and 2010. Body weight was determined at different time points over the pre- and post-weaning phase, and sex, season of birth, litter information (litter size at day of birth and after cross-fostering, number of piglets born alive per litter, number of total born littermates, sow parity number), cross-fostered animals (yes or no), and pen group size over the post-weaning period were recorded. A risk factor analysis approach was used to analyze the datasets to determine factors that predict piglet bw at the end of the nursery period. Body weight at the end of the nursery period corrected for age was mainly determined by season (P < 0.001), birth weight (BiW, P < 0.001), weaning weight (WW, P < 0.001), and BW at 6 wk of age (P < 0.001). These variables were consistent among datasets and explained approximately 70% of the overall variation in BW at the end of the nursery period. Litter information did not significantly (P > 0.05) contribute to explaining the BW at the end of the nursery period. To discard the possibility of intrauterine growth retarded piglets (IUGR) being the reason for the influence of BiW as an explanatory factor in the regression model, a further analysis was performed on the effect of this category of piglets on the results of the regression analysis. Overall, it was concluded that the bw of piglets at the end of the nursery phase is mainly determined by season, sex, birth, WW, and BW at 6 wk of age. Piglets with a BiW greater than the mean biw minus 2.5 times the sd have the potential to compensate during the subsequent phases of growth.

Diaphragm muscle fiber function and structure in humans with hemidiaphragm paralysis.

Recent studies proposed that mechanical inactivity of the human diaphragm during mechanical ventilation rapidly causes diaphragm atrophy and weakness. However, conclusive evidence for the notion that diaphragm weakness is a direct consequence of mechanical inactivity is lacking. To study the effect of hemidiaphragm paralysis on diaphragm muscle fiber function and structure in humans, biopsies were obtained from the paralyzed hemidiaphragm in eight patients with hemidiaphragm paralysis. All patients had unilateral paralysis of known duration, caused by en bloc resection of the phrenic nerve with a tumor. Furthermore, diaphragm biopsies were obtained from three control subjects. The contractile performance of demembranated muscle fibers was determined, as well as fiber ultrastructure and morphology. Finally, expression of E3 ligases and proteasome activity was determined to evaluate activation of the ubiquitin-proteasome pathway. The force-generating capacity, as well as myofibrillar ultrastructure, of diaphragm muscle fibers was preserved up to 8 wk of paralysis. The cross-sectional area of slow fibers was reduced after 2 wk of paralysis; that of fast fibers was preserved up to 8 wk. The expression of the E3 ligases MAFbx and MuRF-1 and proteasome activity was not significantly upregulated in diaphragm fibers following paralysis, not even after 72 and 88 wk of paralysis, at which time marked atrophy of slow and fast diaphragm fibers had occurred. Diaphragm muscle fiber atrophy and weakness following hemidiaphragm paralysis develops slowly and takes months to occur.

Levosimendan improves calcium sensitivity of diaphragm muscle fibres from a rat model of heart failure.

BACKGROUND AND PURPOSE: Diaphragm muscle weakness occurs in patients with heart failure (HF) and is associated with exercise intolerance and increased mortality. Reduced sensitivity of diaphragm fibres to calcium contributes to diaphragm weakness in HF. Here we have investigated the ability of the calcium sensitizer levosimendan to restore the reduced calcium sensitivity of diaphragm fibres from rats with HF. EXPERIMENTAL APPROACH: Coronary artery ligation in rats was used as an animal model for HF. Sham-operated rats served as controls. Fifteen weeks after induction of HF or sham operations animals were killed and muscle fibres were isolated from the diaphragm. Diaphragm fibres were skinned and activated with solutions containing incremental calcium concentrations and 10 µM levosimendan or vehicle (0.02% DMSO). Developed force was measured at each calcium concentration, and force-calcium concentration relationships were plotted. KEY RESULTS: Calcium sensitivity of force generation was reduced in diaphragm muscle fibres from HF rats, compared with fibres from control rats (P < 0.01). Maximal force generation was ∼25% lower in HF diaphragm fibres than in control fibres (P < 0.05). Levosimendan significantly increased calcium sensitivity of force generation in diaphragm fibres from HF and control rats, without affecting maximal force generation. CONCLUSIONS AND IMPLICATIONS: Levosimendan enhanced the force generating capacity of diaphragm fibres from HF rats by increasing the sensitivity of force generation to calcium concentration. These results provide strong support for testing the effect of calcium sensitizers on diaphragm muscle weakness in patients with HF.

Heart failure decreases passive tension generation of rat diaphragm fibers.

BACKGROUND: Diaphragm dysfunction is well-known to limit quality of life and prognosis of patients with heart failure (HF), but its underlying mechanisms are not well understood. In an animal model for HF we recently showed that impaired diaphragm contractility arises at the single fiber level and is associated with sarcomeric injuries. For optimal muscle function and sarcomeric stability passive elastic structures, like titin, are indispensable. The current study aimed to investigate if impaired passive elasticity contributes to diaphragm dysfunction in rats with heart failure. METHODS: Skinned muscle fibers were isolated from the diaphragm and soleus of rats with chronic HF, induced by left coronary artery ligation and of sham-operated rats. Passive tension-length relationships were determined by applying segmental extension tests. Immunofluorescence was performed on muscle cryosections using antibodies (T12) against a titin epitope near the Z-line. Titin content was determined by SDS-agarose-gel electrophoresis. Titin's mobility on gel was studied to detect changes in titin size. RESULTS: Passive tension generation upon stretch was significantly reduced (>35%) in HF diaphragm fibers compared to sham. Immunostaining intensities against titin were reduced in diaphragm cryosections of HF rats compared to sham. Soleus fibers from HF and sham rats did not display differences, neither in passive tension nor in immunostaining. No differences in titin's size were detected in HF and sham diaphragm. Titin content, however, was significantly reduced ( approximately 25%) in HF diaphragm. DISCUSSION: We conclude that in the diaphragm of HF rats, passive elasticity is impaired, mainly resulting from titin loss.

Nonperturbative heavy-quark diffusion in the quark-gluon plasma.

We evaluate heavy-quark (HQ) transport properties in a quark-gluon plasma (QGP) within a Brueckner many-body scheme employing interaction potentials extracted from thermal lattice QCD. The in-medium T matrices for elastic charm- and bottom-quark scattering off light quarks in the QGP are dominated by attractive meson and diquark channels which support resonance states up to temperatures of ~1.5T(c). The resulting drag coefficient increases with decreasing temperature, contrary to expectations based on perturbative QCD scattering. Employing relativistic Langevin simulations we compute HQ spectra and elliptic flow in sqrt[s(NN)]=200 GeV Au-Au collisions. A good agreement with electron decay data supports our nonperturbative computation of HQ diffusion, indicative for a strongly coupled QGP.