Hybrid delivery of cluster-set resistance training for individuals previously treated for lung cancer: the results of a single-arm feasibility trial.

BACKGROUND: Individuals with non-small cell lung cancer (NSCLC) are burdened by long-lasting symptoms (e.g., dyspnea and fatigue) post-treatment. These symptoms often reduce physical activity levels and increase the risk of functional decline. Though we have previously proposed cluster-set resistance training to mitigate symptom burden in lung cancer, there is currently no data on the feasibility or acceptability of this mode of exercise in cancer. Therefore, the purpose of this study was to investigate the feasibility and acceptability of a hybrid-delivery home-based cluster-set resistance training program in individuals with NSCLC stages I-III (i.e., early stage). METHODS: This study aimed to recruit individuals with NSCLC stages I-III post-treatment to participate in 8 weeks of home-based resistance training, 3 days per week. The program included supervised sessions in the participants' homes and virtual supervision via videoconferencing. The primary outcome measure of feasibility was evaluated through recruitment, retention, and intervention fidelity (i.e., proportion of exercise completed, relative to what was prescribed). Intervention acceptability (i.e., ease and quality of virtual delivery, level of difficulty, and home-based approach) was assessed using a 4-point Likert-type scale from "strongly disagree" to "strongly agree". RESULTS: Fourteen participants were recruited over a 6-month period, with 11 completing the intervention (2 withdrew due to unrelated illness, 1 withdrew due to requiring active treatment), yielding a retention rate of 79%. Characteristics of the participants who completed the intervention (n = 11) were as follows: mean age: 71 ± 10 years, mean BMI: 29.1 ± 6.5, and average time since diagnosis was 62 ± 51 months. Of completers, 27% were male, and 36% were Black; 10 were stage I (91%), and one was stage II (9%). Mean session attendance was 86.4 ± 9.5%. Mean intervention fidelity was 83.1 ± 13.1%. With regard to acceptability, > 90% of participants positively rated all aspects of the intervention delivery. No adverse events related to exercise were recorded. CONCLUSIONS: The hybrid delivery of a home-based resistance exercise program for individuals previously treated for early-stage NSCLC was found to be safe and feasible. Adaptations to the program for future interventions are required, particularly surrounding resistance exercise programming, and intervention delivery with home visits. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05014035 . Registered January 20, 2021.

Fat and protein metabolism in growing steers fed either grass silage or dried grass.

Cattle fed grass silage diets have been reported to have high carcass fat:protein ratios. The effect of grass silage and dried grass diets, fed at different levels of intake to ensure a range of equivalent metabolisable energy intakes (MEI) from 1 .1 x metabolisable energy requirement for maintenance to ad libitum, on fat and protein metabolism in twenty-four Hereford x Friesian steers was investigated. After about 84 d of dietary treatment rates of whole-body fat and protein metabolism were measured, as were rates of lipogenesis in omental, perirenal and subcutaneous adipose tissue. Carcass composition was determined. Animals fed silage had greater (P<0 .001) carcass fat:protein ratios than animals fed dried grass at equivalent levels of MEI. Animals fed silage had lower (P<0 .001) rates of protein gain. Rates of leucine entry and oxidation were lower (P<0 .001) in animals fed silage, but there was no dietary difference in the rate of whole-body protein synthesis. There was no dietary difference in the rate of carcass fat gain, but rates of lipogenesis in perirenal adipose tissue were significantly (P=0 .007) higher in animals fed silage. There was no dietary difference in the rate of palmitate and glycerol entry or palmitate oxidation. There were no interactions between MEI and diet, indicating that increments of energy were utilised with the same efficiency from both diets. It was concluded that the high carcass fat:protein ratios of young growing steers was due to limited rates of protein accretion and not to elevated rates of carcass fat accretion.

Grating-enhanced through-wafer optical microprobe for microelectromechanical system high-resolution optical position feedback.

We present modeling and experimental results from the use of a 1310-nm-wavelength through-wafer optical microprobe in conjunction with a microstructure grating to monitor the motion of a lateral comb resonator stage. The optical signal that results from shuttle interaction with the microprobe beam exhibits a peak-to-valley dynamic range that corresponds to 2-microm microstructure displacement, facilitating submicrometer positional resolution on digitization. This signal was used to achieve microstructure positional feedback and effective microsystem model parameter extraction, which are essential for structure control and model-based fault detection.

Collagen expression and biomechanical response to human recombinant transforming growth factor beta (rhTGF-beta2) in the healing rabbit MCL.

We investigated biomechanical and collagen expression in a healing bilateral rabbit medial collateral ligament (MCL) model to human recombinant transforming growth factor beta (rhTGF-beta2) at three and six weeks. Each rabbit had rhTGF-beta2 in a bioabsorbable pellet administered in one side, with the contralateral side serving as control (no rhTGF-beta2). All MCL healed with rhTGF-beta2 producing a profoundly increased scar mass at three weeks which decreased in size toward control at six weeks. In-situ hybridization demonstrated collagen expression (type I and III) no different than control at three weeks, but by six weeks elevated expression of type I was seen. Biomechanical analysis at three weeks showed no effect of rhTGF-beta2 on structural properties. However, at six weeks rhTGF-beta2 significantly inhibited both the maximum load (p < 0.05) and energy absorbed (p < 0.05) with no change in stiffness. Despite increased type I collagen expression and profound increase in early scar mass, rhTGF-beta2 did not improve the structural properties. Whether the dose or mode of delivery is responsible for decline in structural properties cannot be determined in this design. We hypothesize investigations of healing ligaments to cytokines should have biologic and biomechanical properties correlated in the same study at a minimum of two time points.

In vivo macrophage recruitment by murine intervertebral disc cells.

SUMMARY: An in vivo murine experiment was conducted to measure the capacities of viable intervertebral disc cells to recruit inflammatory cells. The objective was to determine whether compounds secreted from viable cells induce inflammation or whether inflammation in disc herniation simply requires exposure to structural cell or matrix components. Three tissue preparations were inserted into the right lower peritoneal cavity of male mice: tissue with viable annulus fibrosus and nucleus pulposus cells, tissue with viable annulus fibrosus cells, or devitalized annulus fibrosus and nucleus pulposus tissue. Controls included sham-operated and nonoperated groups. Mice were killed 1, 2, or 7 days after surgery. Macrophage recruitment occurred after exposure to viable disc tissue but not after exposure to devitalized disc components; recruitment increased over time. Viable disc cells play a role in the etiology of inflammation in disc herniation.

In vivo measurement of lipogenesis in ruminants using [1-(14)C]acetate.

A method for the measurement of the rate of lipogenesis in ruminants using a continuous intravenous infusion of [1-(14)C]acetate and measuring the rate of [1-(14)C]acetate incorporation into adipose tissue lipid was evaluated. Subcutaneous adipose tissue samples obtained by biopsy over the course of a 6 h continuous intravenous infusion of [1-(14)C]acetate into a wether and a steer maintained in a 'metabolic steady state' demonstrated that the incorporation of [1-(14)C]acetate into subcutaneous adipose tissue lipid was linear for the duration of the infusion period. Subsequent measures of rates of [1-(14)C]acetate incorporation into adipose tissue lipid were made on adipose tissue samples taken at a single time point during the infusion period. The technique was used to measure rates of lipogenesis in the subcutaneous adipose tissue of fourteen Hereford x Friesian steers that had been fed a pelleted diet of dried grass at a range of metabolizable energy (ME) intakes from 1.1 x ME requirement for maintenance to ad libitum for 11 weeks. Rates of lipogenesis increased linearly with increasing ME intake. It was concluded that the method is an effective technique for measuring rates of lipogenesis in specific adipose tissue depots in vivo in ruminants.

Growth factor modulation of distraction osteogenesis in a segmental defect model.

A model was established in 39 dogs to investigate the growth factor modulation of regenerate bone in distraction osteogenesis. A segment of the diaphysis of the radius was resected unilaterally. An osteotomy was made proximal to the segmental defect to create a transport segment. A monolateral external fixator was applied. After a latency period, the segment was transported across the defect. One week after the transport assembly contacted the distal pin clamp, an ipsilateral osteotomy of the proximal ulna was performed. In 20 dogs, transforming growth factor-beta was injected into the regenerate bone halfway through the transport period. Four dogs were sacrificed before docking, when the regenerate bone was still immature. In specimens harvested halfway through the transport period, evidence was found of intramembranous ossification during distraction. In specimens harvested after the transport assembly contacted the distal pin clamp, evidence was found that the mature regenerate formed by endochondral ossification. Therefore, a combined mechanism of ossification is proposed for this segmental defect model that includes mechanical stimulus for bone differentiation. The one-time administration of transforming growth factor-beta retarded the formation of a stable, united regenerate. It is concluded that transforming growth factor-beta caused an effect opposite to that which was desired.

Maternal nutrition alters the expression of insulin-like growth factors in fetal sheep liver and skeletal muscle.

We investigated the influence of maternal dietary restriction between days 28 and 80 of gestation followed by re-feeding to the intake of well-fed ewes up to 140 days of gestation (term is 147 days) in sheep, on expression of mRNA for insulin-like growth factor (IGF)-I, IGF-II and growth hormone receptor (GHR) in fetal liver and skeletal muscle. Singleton bearing ewes either consumed 3.2-3.8 MJ/day of metabolisable energy (ME) (i.e. nutrient restricted - approximately 60% of ME requirements, taking into account requirements for both ewe maintenance and growth of the conceptus) or 8.7-9.9 MJ/day (i.e. well fed - approximately 150% of ME requirements) between days 28 and 80 of gestation. All ewes were then well fed (150% of ME requirements) up to day 140 of gestation and consumed 8-10.9 MJ/day. At days 80 and 140 of gestation, five ewes were sampled from each group and fetal tissues taken. There was no difference in fetal body weight or liver weights between groups at either sampling date, or skeletal muscle (quadriceps) weight at 140 days. IGF-I mRNA abundance was lower in livers of nutrient-restricted fetuses at day 80 of gestation (nutrient restricted 2.35; well fed 3.70 arbitrary units), but was higher than well-fed fetuses at day 140 of gestation, after 60 days of re-feeding (restricted/re-fed 4.27; well fed 2.83;s.e.d. 0.98 arbitrary units, P=0.061 for dietxage interaction). IGF-II mRNA abundance was consistently higher in livers of nutrient-restricted fetuses (80 days: nutrient restricted 7.78; well fed 5.91; 140 days: restricted/re-fed 7.23; well fed 6.01;s.e.d. 1.09 arbitrary units, P=0.061 for diet). Nutrient restriction had no effect on hepatic GHR mRNA abundance, but re-feeding of previously nutrient-restricted fetuses increased GHR mRNA compared with continuously well-fed fetuses (80 days: nutrient restricted 70.6; well fed 75.1; 140 days: restricted/re-fed 115.7; well fed 89.4;s.e.d. 10.13 arbitrary units, P=0.047 for dietxage interaction). In fetal skeletal muscle, IGF-I mRNA abundance was not influenced by maternal nutrition and decreased with gestation age (P<0.01). IGF-II mRNA abundance was higher in skeletal muscle of nutrient-restricted fetuses compared with well-fed fetuses at day 80 of gestation (nutrient restricted 16.72; well fed 10.53 arbitrary units), but was lower than well-fed fetuses after 60 days of re-feeding (restricted/re-fed 7.77; well fed 13.72;s.e.d. 1.98 arbitrary units, P<0.001 for dietxage interaction). There was no effect of maternal nutrition or gestation age on fetal skeletal muscle GHR expression. In conclusion, maternal nutrient restriction in early to mid gestation with re-feeding thereafter results in alterations in hepatic and skeletal muscle expression of IGF-I, IGF-II and/or GHR in the fetus which may subsequently relate to altered organ and tissue function.

Gastrointestinal transit times in young and old cats.

Ageing results in a decrease in apparent nutrient digestibility in the gastrointestinal (GI) tract. The aim of this study was to investigate whether the rate of gastric emptying or total GI transit times differed between young (3.0+/-0.9 years) and senior (11.6+/-1. 4 years) cats. Gastric emptying rates were measured using [1-(13)C]octanoic acid and total transit times with chromium oxide. No significant differences (P>0.05) were observed in either the rate of gastric emptying or total transit time between young and senior cats although senior cats exhibited a larger variability in total transit time compared to the younger cats (35.71+/-14.06 and 26. 46+/-5.80 h, respectively). The results of this study indicate that the observed reduction in nutrient digestibility in ageing cats is not due to alterations in the rate of passage of digesta through the GI tract.

Quantitative proton magnetic resonance spectroscopy of the subcortical white matter in motor neuron disease.

BACKGROUND: Using proton magnetic resonance spectroscopy, the authors have previously demonstrated a reduction in the N-acetyl aspartate/(creatine and phosphocreatine) (NAA/(Cr + PCr)) ratio in the motor region in bulbar-onset MND patients, attributed to neuronal loss or dysfunction leading to a reduction in NAA. We have expanded this analysis to evaluate absolute concentrations of NAA, (Cr + PCr) and choline-containing compounds (Cho) in the subcortical white matter in the motor region in 16 MND patients (8 with bulbar onset and 8 with limb onset) and 8 healthy, age-matched controls. METHODS: Single voxel 1H-MRS was performed using a PRESS localization sequence. Metabolite concentrations were determined using the water signal as an internal standard. RESULTS: We found no differences in the concentrations of NAA ([NAA]), (Cr + PCr) ([Cr + PCr]) or Cho ([Cho]) in the motor region on comparing the total MND group and controls (P > 0.3). No difference was found in [NAA] in the bulbar-onset group compared with the limb-onset group (P = 0.70), but [Cr + PCr] was significantly higher in the bulbar-onset group (P = 0.04). CONCLUSIONS: Our results suggest that [Cr + PCr] may be affected by the pathological process in MND, and this should be considered in the interpretation of metabolite peak area ratios. The elevated (Cr + PCr) may represent gliosis in the subcortical white matter in the motor cortex region.

Diffusion tensor MRI assesses corticospinal tract damage in ALS.

BACKGROUND: A number of neurophysiologic and neuroimaging techniques have been evaluated in the research setting to assess upper motor neuron (UMN) damage in ALS. Changes in tissue structure in the CNS modify the diffusional behavior of water molecules, which can be detected by diffusion tensor MRI. OBJECTIVES: To explore the hypothesis that degeneration of the motor fibers in ALS would be reflected by changes in the diffusion characteristics of the white matter fibers in the posterior limb of the internal capsule and that these changes could be detected by diffusion tensor MRI. METHODS: We studied 22 patients with El Escorial definite, probable, or possible ALS-11 with limb onset (mean age 54.5 +/- 10.7 years) and 11 with bulbar onset (mean age 49.6 +/- 11.7 years)-and compared them with 20 healthy, age-matched controls (mean age 46.0 +/- 12.6 years). We assessed central motor conduction time (CMCT), threshold to stimulation, and silent period using transcranial magnetic stimulation. Diffusion tensor MRI was performed using a 1.5-T GE Signa system (Milwaukee, WI) fitted with Advanced NMR hardware and software capable of producing echo planar MR images. Data were acquired from seven coronal slices centered to include the posterior limb of the internal capsule. Maps of the mean diffusivity, fractional anisotropy, and T2-weighted signal intensity were generated. RESULTS: There were no differences between the subject groups on measures of CMCT, threshold to stimulation, and silent period. However, the CMCT correlated with clinical measures of UMN involvement. We found a significant increase in the mean diffusivity and reduction in fractional anisotropy along the corticospinal tracts between the three subject groups, most marked in the bulbar-onset group. The fractional anisotropy correlated with measures of disease severity and UMN involvement, whereas the mean diffusivity correlated with disease duration. CONCLUSION: The results support the use of diffusion tensor MRI in detecting pathology of the corticospinal tracts in ALS.

Comparative biomechanics of hybrid external fixation.

OBJECTIVE: To compare the elastic stiffness, in several loading modes, of commercially available hybrid external fixation systems. DESIGN: Laboratory investigation using a polyvinylchloride pipe periarticular tibia fracture model. SETTING: Simulated periarticular fractures were created in an in vitro tibia fracture model. Instrumented specimens and intact controls were elastically tested in a biomaterials testing system. INTERVENTION: Groups of simulated periarticular tibia fractures were stabilized with one of six different hybrid external fixator designs. MAIN OUTCOME MEASUREMENTS: Elastic stiffness of each specimen was measured in compression, torsion, flexion bending, extension bending, and varus/valgus bending. RESULTS: Fixators with multiple levels of fixation in the periarticular fragment, regardless of design, were stiffer than those with one level. Specifically, the EBI Ring Connector fixator was stiffer than all others in all modes of testing. The Ace, Synthes, Smith & Nephew Richards, and How medica fixators were mechanically similar. The Zimmer Torus fixator was the least stiff fixator tested. CONCLUSIONS: Fixators with multiple levels of fixation in the periarticular fragment, regardless of design, were stiffer than those with one level. The choice of which hybrid external fixator to use should be made based not only on stiffness but also on ease of clinical application, patient comfort, customer support from the manufacturer, and cost. Clinical investigation of the efficacy of each of these devices is warranted.

Effect of gastric inhibitory polypeptide on bovine fat metabolism.

Gastric inhibitory polypeptide (GIP), a hormone secreted by the gastrointestinal tract in response to nutrient absorption, exerts anabolic effects on adipose tissue in some species. Cattle fed on grass silage diets tend to deposit more fat than animals fed on dried forages. We investigated the effect of diet on blood GIP concentrations in cattle. Plasma concentrations tended to be higher in cattle fed grass silage alone or supplemented with fishmeal (0.61 ng/ml) compared with animals fed dried grass/barley (0.43 ng/ml, P > 0.1) and were inversely correlated with plasma insulin concentrations (r = -0.727, P < 0.01). The effects of increasing concentrations (0, 0.1, 1.0, 10.0 nM) of GIP and glucagon-like peptide-1 (GLP-1) on basal and insulin-stimulated lipogenesis in bovine adipose tissue in vitro were investigated after 4 and 24 h of incubation. No conclusive effects were obtained with either peptide. Subsequently, the effect of exogenous administration of GIP (10 or 50 ng/kg liveweight per min) on whole-body fat metabolism was investigated in two steers in vivo. Plasma concentration and flux rate of palmitate was increased by GIP only at the higher infusion level suggesting lipolysis and possibly fatty acid re-esterification was stimulated at high concentration. We conclude that although gut peptides may regulate nutrient utilisation, it is unlikely that they play a major role in promoting fat accretion in cattle. However, the small number of animals used in these studies indicates the need for caution and further studies are warranted.

The use of vancomycin and tobramycin in acrylic bone cement: biomechanical effects and elution kinetics for use in joint arthroplasty.

We examined the effects of vancomycin on the compressive strength and fatigue life of bone cement and the pharmacokinetics and antimicrobial activity against methicillin-resistant Staphylococcus aureus of vancomycin eluted from bone cement, both alone and in combination with tobramycin. Two cements, Palacos and Simplex, were tested. Three antibiotic preparations were tested: lyophilized vancomycin (vancomycin-L), vancomycin powder (vancomycin-P), and tobramycin powder (Lilly, Indianapolis, IN). Although antibiotics did not significantly affect compressive strength, the fatigue life of bone cement was significantly decreased with vancomycin. Thus, fatigue testing revealed effects on cement strength not apparent by compression testing. Vancomycin-P had a substantially less detrimental effect on fatigue strength than vancomycin-L. Vancomycin-P elutes less efficiently than tobramycin. Although relatively little vancomycin-P eluted from bone cement, it retained biologic activity.

Analysis of the structural behavior of the pelvis during lateral impact using the finite element method.

In this study, three-dimensional finite element models were created from computer tomography data to study lateral impact fractures of the pelvis. The models reflect the complex geometry and material properties of the pelvis. The models were compared to published experimental results for validation. Dynamic analyses of the pelvic structure were performed for different peak forces in the range of 5520 to 15550 N to correspond to the velocities and impulses of real world accidents. The locations of structurally significant regions of the pelvis were identified based upon the stress distribution and upon the energy stored by the pelvis to failure. The impact force which induced fracture of the pelvic bone was 8610 N. The region which failed first in left lateral impact was the right pubic ramus. The fracture pattern was a variant of the lateral compression pelvic injury. The results suggest that the anterior structures of the pelvis are the most sensitive regions. The energy absorbed by the pelvis prior to failure was 8.98 J. The finite element method may be used to determine the strength and energy-absorbing capability of the pelvis for lateral impact loading.

Estrogen levels in girls with premature thelarche compared with normal prepubertal girls as determined by an ultrasensitive recombinant cell bioassay.

OBJECTIVE: Estradiol levels in girls with premature thelarche have not previously been well defined because of the lack of adequate sensitivity of previously available estradiol assays. The ultrasensitive recombinant cell bioassay for estradiol has made the study of estradiol levels in premature thelarche possible. We hypothesized that girls with premature thelarche have higher estradiol levels than normal prepubertal girls. STUDY DESIGN: We used an ultrasensitive recombinant cell bioassay to study estradiol levels in 20 girls with premature thelarche and 15 normal prepubertal girls less than 3 years of age. The 2 groups were compared by Student t test. RESULTS: Estradiol levels were significantly greater in the girls with premature thelarche (8.4 4. 5 pmol/L estradiol equivalents) than in the normal prepubertal girls (3.3 3.5 pmol/L estradiol equivalents; P <.01). The estradiol level was not significantly correlated with age, height, weight, body mass index, age at onset of thelarche, or the presence or absence of ovarian cysts. CONCLUSION: Girls with premature thelarche have significantly higher estradiol levels than normal prepubertal girls. This is consistent with the hypothesis that the mechanism of premature thelarche involves increased estradiol levels rather than increased sensitivity of breast tissue to normal estradiol levels.

The biomechanics of hybrid external fixation.

OBJECTIVE: The objective of this study was to ascertain which factors determine the rigidity of a hybrid external fixation frame in a tibial periarticular fracture model. DESIGN: Laboratory investigation using a polyvinylchloride pipe periarticular tibia fracture model. SETTING: Simulated periarticular tibia fractures were created in a tibia model. Instrumented specimens were tested in a biomaterials testing system. INTERVENTION: Groups of simulated periarticular tibia fractures were stabilized with one of nine different external fixation constructs with components from one manufacturer. MAIN OUTCOME MEASUREMENTS: Elastic stiffness was measured for each specimen in compression, torsion, flexion bending, extension bending, and varus and valgus bending. RESULTS: The four-ring Ilizarov fixator was the stiffest in all modes of testing. There was a trend toward increasing stiffness with an increasing number of rings. Fixators constructed with multiple levels of fixation in the periarticular fragment were stiffer in all modes of testing. The additional spacing between wires gained by the use of a single thick carbon ring or the use of a drop wire three centimeters from a single ring did not increase stiffness in this model. Frame modifications intended to augment the bar-to-ring connection did not increase stiffness. The use of rings mounted with half-pins instead of a unilateral bar mounted with half-pins for diaphyseal fixation increased the stiffness of the frame only in torsional testing. CONCLUSIONS: Although the ideal stiffness of an external fixator is unknown, our results show that the addition of more than one level of fixation in the periarticular fragment increases the stiffness of hybrid external fixators in this periarticular tibia fracture model. Augmentation of the ring-to-bar connection did not significantly affect the stiffness of the frame.

The effect of ageing on nutrient digestibility by cats fed beef tallow-, sunflower oil- or olive oil-enriched diets.

Nutrient digestibility and absorption decline with age in several mammalian species. The aim of this study was to compare apparent fat digestibility of different dietary fats in young and senior cats. Three diets enriched with either beef tallow (high in saturated fatty acids), olive oil (high in monounsaturated fatty acids) or sunflower oil (high in polyunsaturated fatty acids) were fed to 6 young (3.0+/-0.9y) and 6 senior (11.6+/-1.4y) cats at 300kJ metabolisable energy/kgBW0.75/d in a 3*3 Latin square design. Food and faecal samples collected over two consecutive 7d periods were analysed for fat, protein, moisture, ash, gross energy and fatty acid content. Apparent digestibilities of fat and energy were significantly lower (P=0.03) in senior cats compared to young cats (fat: 0.922 compared to 0.944; energy: 0.848 compared to 0.885, for senior and young cats, respectively) in all three diets. Senior cats exhibited a lower apparent digestibility for all fatty acid groups compared to the younger cats (saturated: 0.932 compared to 0.952; monounsaturated: 0.964 compared to 0.982; polyunsaturated: 0.980 compared to 0.987, for senior and young cats, respectively). Saturated fatty acids had the lowest apparent digestibility in both young and senior cats, and shorter chain fatty acids were digested more easily than the longer chain fatty acids. These results suggest that the age-related reduction in apparent fat digestibility was a general phenomenon affecting all fatty acids, and was not due to one particular fatty acid group.