Impact of methodological choices in comparative effectiveness studies: application in natalizumab versus fingolimod comparison among patients with multiple sclerosis.

BACKGROUND: Natalizumab and fingolimod are used as high-efficacy treatments in relapsing-remitting multiple sclerosis. Several observational studies comparing these two drugs have shown variable results, using different methods to control treatment indication bias and manage censoring. The objective of this empirical study was to elucidate the impact of methods of causal inference on the results of comparative effectiveness studies. METHODS: Data from three observational multiple sclerosis registries (MSBase, the Danish MS Registry and French OFSEP registry) were combined. Four clinical outcomes were studied. Propensity scores were used to match or weigh the compared groups, allowing for estimating average treatment effect for treated or average treatment effect for the entire population. Analyses were conducted both in intention-to-treat and per-protocol frameworks. The impact of the positivity assumption was also assessed. RESULTS: Overall, 5,148 relapsing-remitting multiple sclerosis patients were included. In this well-powered sample, the 95% confidence intervals of the estimates overlapped widely. Propensity scores weighting and propensity scores matching procedures led to consistent results. Some differences were observed between average treatment effect for the entire population and average treatment effect for treated estimates. Intention-to-treat analyses were more conservative than per-protocol analyses. The most pronounced irregularities in outcomes and propensity scores were introduced by violation of the positivity assumption. CONCLUSIONS: This applied study elucidates the influence of methodological decisions on the results of comparative effectiveness studies of treatments for multiple sclerosis. According to our results, there are no material differences between conclusions obtained with propensity scores matching or propensity scores weighting given that a study is sufficiently powered, models are correctly specified and positivity assumption is fulfilled.

Modulation of soleus stretch reflexes during walking in people with chronic incomplete spinal cord injury.

In people with spasticity due to chronic incomplete spinal cord injury (SCI), it has been presumed that the abnormal stretch reflex activity impairs gait. However, locomotor stretch reflexes across all phases of walking have not been investigated in people with SCI. Thus, to understand modulation of stretch reflex excitability during spastic gait, we investigated soleus stretch reflexes across the entire gait cycle in nine neurologically normal participants and nine participants with spasticity due to chronic incomplete SCI (2.5-11 year post-injury). While the participant walked on the treadmill at his/her preferred speed, unexpected ankle dorsiflexion perturbations (6° at 250°/s) were imposed every 4-6 steps. The soleus H-reflex was also examined. In participants without SCI, spinal short-latency "M1", spinal medium latency "M2", and long-latency "M3" were clearly modulated throughout the step cycle; the responses were largest in the mid-stance and almost completely suppressed during the stance-swing transition and swing phases. In participants with SCI, M1 and M2 were abnormally large in the mid-late-swing phase, while M3 modulation was similar to that in participants without SCI. The H-reflex was also large in the mid-late-swing phase. Elicitation of H-reflex and stretch reflexes in the late swing often triggered clonus and affected the soleus activity in the following stance. In individuals without SCI, moderate positive correlation was found between H-reflex and stretch reflex sizes across the step cycle, whereas in participants with SCI, such correlation was weak to non-existing, suggesting that H-reflex investigation would not substitute for stretch reflex investigation in individuals after SCI.

IUGR decreases cardiomyocyte endowment and alters cardiac metabolism in a sex- and cause-of-IUGR-specific manner.

Intrauterine growth restriction (IUGR) increases the risk of ischemic heart disease in adulthood. Studies in rats suggest cardiac vulnerability is more pronounced in males and in offspring that were exposed to hypoxia in utero. Therefore, we aimed to test the hypotheses that 1) IUGR adolescent males, but not females, have fewer cardiomyocytes and altered expression of cardiometabolic genes compared with controls; and 2) IUGR due to hypoxia has a greater effect on these parameters compared with IUGR due to nutrient restriction. IUGR was induced in guinea pigs by maternal hypoxia (MH; 10% O2, n = 9) or maternal nutrient restriction (MNR; ~30% reduction in food intake, n = 9) in the second half of pregnancy and compared with control ( n = 11). At 120 days of age, postmortem was performed and the left ventricle perfusion fixed for stereological determination of cardiomyocyte number or snap frozen to determine the abundance of cardiometabolic genes and proteins by quantitative RT-PCR and Western blotting, respectively. MH reduced the number of cardiomyocytes in female ( P < 0.05), but not male or MNR, adolescent offspring. Furthermore, IUGR males had decreased expression of genes responsible for fatty acid activation in the sarcoplasm ( FACS) and transport into the mitochondria ( AMPK-a2 and ACC; P < 0.05) and females exposed to MH had increased activation/phosphorylation of AMP-activated protein kinase-α ( P < 0.05). We postulate that the changes in cardiomyocyte endowment and cardiac gene expression observed in the present study are a direct result of in utero programming, as offspring at this age did not suffer from obesity, hypertension, or left ventricular hypertrophy.

Differential effects of FXR or TGR5 activation in cholangiocarcinoma progression.

BACKGROUND AND AIMS: Cholangiocarcinoma (CCA) is an aggressive tumor type affecting cholangiocytes. CCAs frequently arise under certain cholestatic liver conditions. Intrahepatic accumulation of bile acids may facilitate cocarcinogenic effects by triggering an inflammatory response and cholangiocyte proliferation. Here, the role of bile acid receptors FXR and TGR5 in CCA progression was evaluated. METHODS: FXR and TGR5 expression was determined in human CCA tissues and cell lines. An orthotopic model of CCA was established in immunodeficient mice and tumor volume was monitored by magnetic resonance imaging under chronic administration of the specific FXR or TGR5 agonists, obeticholic acid (OCA) or INT-777 (0,03% in chow; Intercept Pharmaceuticals), respectively. Functional effects of FXR or TGR5 activation were evaluated on CCA cells in vitro. RESULTS: FXR was downregulated whereas TGR5 was upregulated in human CCA tissues compared to surrounding normal liver tissue. FXR expression correlated with tumor differentiation and TGR5 correlated with perineural invasion. TGR5 expression was higher in perihilar than in intrahepatic CCAs. In vitro, FXR was downregulated and TGR5 was upregulated in human CCA cells compared to normal human cholangiocytes. OCA halted CCA growth in vivo, whereas INT-777 showed no effect. In vitro, OCA inhibited CCA cell proliferation and migration which was associated with decreased mitochondrial energy metabolism. INT-777, by contrast, stimulated CCA cell proliferation and migration, linked to increased mitochondrial energy metabolism. CONCLUSION: Activation of FXR inhibits, whereas TGR5 activation may promote, CCA progression by regulating proliferation, migration and mitochondrial energy metabolism. Modulation of FXR or TGR5 activities may represent potential therapeutic strategies for CCA.

Breaking up Prolonged Sitting does not Alter Postprandial Glycemia in Young, Normal-Weight Men and Women.

A randomized, controlled, cross-over study was used to investigate the effects of breaking up prolonged sitting with low intensity physical activity on postprandial blood glucose concentrations in healthy, young, normal-weight adults. 14 men (n=6) and women (n=8) were assigned to 2.5 h of prolonged sitting (CON) and 2.5 h of prolonged sitting with 2-min bouts of walking every 20 min (LIPA). After ingesting a standardized test drink, capillary blood was sampled every 10 min to establish a postprandial blood glucose profile. Based on individual glucose responses, peak blood glucose, time-to-peak glucose, and incremental area under the glucose curve (iAUC) were determined. Paired sample t-tests were used to detect differences between trials. Peak blood glucose (p=0.55) and iAUC (CON: 252 mmol·L-1·2.5 h-1 [163-340]; LIPA: 214 mmol·L-1·2.5 h-1 [146-282]; p=0.45) were not different between trials. Also, time-to-peak glucose was not different between LIPA and CON (p=0.37). Taking advantage of high temporal resolution blood glucose profiles, we showed that breaking up prolonged sitting with low-intensity physical activity does not alter the postprandial blood glucose response in young, healthy, normal-weight adults. Our results indicate that postprandial glycemic control is maintained during prolonged sitting in young, healthy adults.

Myasthenia gravis and risks for comorbidity.

Myasthenia gravis (MG) is an autoimmune disorder leading to skeletal muscle weakness and fatigability. MG subgroups are defined according to pathogenetic autoantibody (against acetylcholine receptor, muscle-specific tyrosine kinase or lipoprotein receptor-related protein 4), thymus pathology and clinical manifestations. MG patients have an increased risk for concordant autoimmune disease, in particular with early onset MG. Most common comorbidities are thyroid disease, systemic lupus erythematosus and rheumatoid arthritis. Cardiomyositis and subclinical heart dysfunction have been described in patients with thymoma MG and late onset MG but represent no major threat. A thymic lymphoepithelioma implies an increased risk for another cancer. Autoimmune MG represents no distinct cancer risk factor, although lymphomas and a few other cancer types have been reported with slightly increased frequency. Severe MG-related muscle weakness means a risk for respiratory failure and respiratory tract infection. Drug MG treatment can lead to side-effects. Thymectomy is regarded as a safe procedure both short and long term. Non-MG-related comorbidity represents a diagnostic and therapeutic challenge, especially in elderly patients. Diagnostic accuracy and optimal follow-up is necessary to identify and treat all types of coexisting disease in MG.

Total drug treatment and comorbidity in myasthenia gravis: a population-based cohort study.

BACKGROUND AND PURPOSE: Comorbidity in myasthenia gravis (MG) is important for diagnosis, treatment and prognosis. Disease complexity was assessed by examining total drug treatment, immune therapy and comorbidity in a complete national MG cohort. METHODS: All recipients of the MG-specific drug pyridostigmine 2004-2010 registered in the compulsory Norwegian Prescription Database who met the inclusion criteria were included. The pyridostigmine group was compared with the general Norwegian population. RESULTS: Myasthenia gravis patients received co-medication more often than the controls for nearly all groups of medication, including insulins (95% confidence interval 2.0-3.7), thyroid therapy (1.7-2.5), antidepressants (1.3-1.7), anti-infectives (1.2-1.4), lipid-modifying agents (1.1-1.4) and immunomodulating agents (6.8-8.8). CONCLUSIONS: Myasthenia gravis patients are more often treated with non-MG prescription drugs than controls, reflecting frequent co-medication and comorbidity.

Myasthenia gravis epidemiology in a national cohort; combining multiple disease registries.

OBJECTIVES: There is a wide variation in reported prevalence and incidence of myasthenia gravis (MG). In this study, we aimed to evaluate the validity of two nationwide databases by comparing prevalence and incidence rates reported from three recent studies using the two databases as case-finding method. MATERIALS AND METHODS: Two different Norwegian nationwide databases were used: the acetylcholine receptor antibody database (reference cohort) and the Norwegian Prescription Database (NorPD) (study cohort). Presence of acetylcholine receptor antibodies (AChR) is specific for MG. Up to 85% of MG patients are AChR antibody-positive. All samples from the whole country were tested at one laboratory. NorPD contains patient information on all prescriptions of pyridostigmine. RESULTS: Prevalence was 131 per million in the study cohort and 145 per million estimated from the reference cohort (Jan 1, 2008). No significant difference in prevalence between the study cohort and the reference cohort was found (SIR 1.1, 95% CI 1.0-1.2). The annual incidence rate was 16.0 per million in the study cohort and 8.8 per million estimated from the reference cohort, twofold more new MG patients were found in the study cohort compared to estimated figures from the reference cohort (SIR 1.8; 1.4-2.3). CONCLUSIONS: This study confirms an optimal and unbiased case finding in both databases. Our calculated prevalence and incidence rates are in line with previous population-based studies. There was good agreement in prevalence reported from the two databases. The discrepancy in incidence is expected to diminish as years of study are increasing in NorPD.

Improving efficiency in stereology: a study applying the proportionator and the autodisector on virtual slides.

Cell counting in stereology is time-consuming. The proportionator is a new stereological sampling method combining automatic image analysis and non-uniform sampling. The autodisector on virtual slides combines automatic generation of disector pairs with the use of digital images. The aim of the study was to investigate the time efficiency of the proportionator and the autodisector on virtual slides compared with traditional methods in a practical application, namely the estimation of osteoclast numbers in paws from mice with experimental arthritis and control mice. Tissue slides were scanned in a digital slide scanner and the autodisector was applied on the obtained virtual tissue slides. Every slide was partitioned into fields of view, and cells were counted in all of them. Based on the original exhaustive data set comprising 100% of fields of view and covering the total section area, a proportionator sampling and a systematic, uniform random sampling were simulated. We found that the proportionator was 50% to 90% more time efficient than systematic, uniform random sampling. The time efficiency of the autodisector on virtual slides was 60% to 100% better than the disector on tissue slides. We conclude that both the proportionator and the autodisector on virtual slides may improve efficiency of cell counting in stereology.

Mutations in isocitrate dehydrogenase 1 and 2 occur frequently in intrahepatic cholangiocarcinomas and share hypermethylation targets with glioblastomas.

Mutations in the genes encoding isocitrate dehydrogenase, IDH1 and IDH2, have been reported in gliomas, myeloid leukemias, chondrosarcomas and thyroid cancer. We discovered IDH1 and IDH2 mutations in 34 of 326 (10%) intrahepatic cholangiocarcinomas. Tumor with mutations in IDH1 or IDH2 had lower 5-hydroxymethylcytosine and higher 5-methylcytosine levels, as well as increased dimethylation of histone H3 lysine 79 (H3K79). Mutations in IDH1 or IDH2 were associated with longer overall survival (P=0.028) and were independently associated with a longer time to tumor recurrence after intrahepatic cholangiocarcinoma resection in multivariate analysis (P=0.021). IDH1 and IDH2 mutations were significantly associated with increased levels of p53 in intrahepatic cholangiocarcinomas, but no mutations in the p53 gene were found, suggesting that mutations in IDH1 and IDH2 may cause a stress that leads to p53 activation. We identified 2309 genes that were significantly hypermethylated in 19 cholangiocarcinomas with mutations in IDH1 or IDH2, compared with cholangiocarcinomas without these mutations. Hypermethylated CpG sites were significantly enriched in CpG shores and upstream of transcription start sites, suggesting a global regulation of transcriptional potential. Half of the hypermethylated genes overlapped with DNA hypermethylation in IDH1-mutant gliobastomas, suggesting the existence of a common set of genes whose expression may be affected by mutations in IDH1 or IDH2 in different types of tumors.

Molecular targeting of CSN5 in human hepatocellular carcinoma: a mechanism of therapeutic response.

Development of targeted therapy for hepatocellular carcinoma (HCC) remains a major challenge. We have recently identified an elevated expression of the fifth subunit of COP9 signalosome (CSN5) in early HCC as compared with dysplastic stage. In the present study, we explored the possibility of CSN5 being a potential therapeutic target for HCC. Our results show that CSN5 knockdown by small-interfering (si) RNA caused a strong induction of apoptosis and inhibition of cell-cycle progression in HCC cells in vitro. The down-regulation of CSN5 was sufficient to interfere with CSN function as evidenced by the accumulation of neddylated Cullin 1 and changes in the protein levels of CSN-controlled substrates SKP2, p53, p27 and nuclear factor-κB, albeit to a different degree depending on the HCC cell line, which could account for the CSN5 knockdown phenotype. The transcriptomic analysis of CSN5 knockdown signature showed that the anti-proliferative effect was driven by a common subset of molecular alterations including down-regulation of cyclin-dependent kinase 6 (CDK6) and integrin ß1 (ITGB1), which were functionally interconnected with key oncogenic regulators MYC and TGFß1 involved in the control of proliferation, apoptotic cell death and HCC progression. Consistent with microarray analysis, western blotting revealed that CSN5 depletion increased phosphorylation of Smad 2/3, key mediators of TGFß1 signaling, decreased the protein levels of ITGB1, CDK6 and cyclin D1 and caused reduced expression of anti-apoptotic Bcl-2, while elevating the levels of pro-apoptotic Bak. A chemically modified variant of CSN5 siRNA was then selected for in vivo application based on the growth inhibitory effect and minimal induction of unwanted immune response. Systemic delivery of the CSN5 3/8 variant by stable-nucleic-acid-lipid particles significantly suppressed the tumor growth in Huh7-luc+ orthotopic xenograft model. Taken together, these results indicate that CSN5 has a pivotal role in HCC pathogenesis and maybe an attractive molecular target for systemic HCC therapy.

The semi-automatic nucleator.

The nucleator is a well-established manual stereological method of estimating mean cell volume from observations on random cell transects through reference points of the cells. In this paper, we present an automated version of the nucleator that uses automatic segmentation of the boundaries of the cell transects. An expert supervises the process. If the segmentation is judged to be satisfactory, an estimate of the cell volume is calculated automatically on the basis of the whole cell transect. In the remaining cases, the expert intervenes and uses the classical nucleator. The resulting estimator is called the semi-automatic nucleator. In this paper, we study the statistical properties of the semi-automatic nucleator. Formulae for the bias and mean square error are derived. The semi-automatic nucleator may have a small bias but will still in most cases be more efficient than the classical nucleator. Procedures for estimating bias and mean square error from a pilot study are provided. The application of the semi-automatic nucleator is illustrated in a study of somatostatin positive inhibitory interneurons which were genetically labelled with green fluorescent protein (GFP). The cells were sampled with an optical disector. The centre of mass in a central cell transect was used as reference point. It is found in this study that the number of cells needed for obtaining, for instance, a 5% precision of the estimate of mean cell volume is 150 and 189 for the semi-automatic and the classical nucleator, respectively. Taking into account that the time spent analysing one cell is shorter for the semi-automatic nucleator than for the classical nucleator, the semi-automatic nucleator is superior to the classical nucleator.

Myasthenia gravis requiring pyridostigmine treatment in a national population cohort.

BACKGROUND: Pyridostigmine is the first drug of choice for patients with myasthenia gravis (MG). The drug is not prescribed regularly to any other patient groups. We aimed to determine the prevalence, incidence and gender-specific characteristics of patients with MG needing drug treatment in a well-defined population cohort. METHODS: Data were retrieved from the Norwegian Prescription Database (NorPD) 2004-2007, containing information on all dispensed drugs in Norway. The study population comprised 677 recipients of pyridostigmine who met the following inclusion criteria (one or more): (i) More than one prescription 1 January 2004-31 December 2007, (ii) prescription from a specialist in neurology, (iii) prescription for MG being specified in NorPD. RESULTS: A total of 435 (64%) women and 242 men were included; female:male ratio 1.8:1. Point prevalence (1 January 2008) of symptomatic MG was 131 per million; 92 for men, 170 for women. Seventy-four new users of pyridostigmine were registered in 2007 (42 women, 32 men), i.e. the incidence rate for 2007 being 16 per million; 14 for men, 18 for women. Mean age of incident cases was 59 years; 64 and 55 years, respectively. Prevalence and incidence were significantly higher in the age group ≥ 50 years than < 50 years (P < 0.001), and highest at 70-79 years. Prevalence and incidence did not differ in the five geographical health regions in Norway. CONCLUSIONS: Reported prevalence and incidence are amongst the highest found in similar studies. This may be explained by optimal case identification, higher incidence of drug requiring MG amongst the elderly, and recurrences of previous MG.

Power variations of wireless communication systems.

The use of wireless digital communication devices like GSM, WCDMA, HSPA, DECT, and WiFi changes the exposure of electromagnetic waves toward the user. Concentrating on the power variations on a slow and fast time scale, these new systems are discussed. Experimental results for both uplink and downlink are included for a sample of systems. The spectrum of the power fluctuations is seen as a convenient and compact way of describing very complex system behavior. The results are of interest for scientific studies of epidemiology and biological effects, and for general electromagnetic compatibility (EMC) aspects.

Analysis of the intestinal microbiota of oligosaccharide fed mice exhibiting reduced resistance to Salmonella infection.

Certain indigestible carbohydrates, known as prebiotics, are claimed to be beneficial for gut health through a selective stimulation of certain gut microbes including bifidobacteria. However, stimulation of such microbes does not necessarily imply a preventive effect against pathogen infection. We recently demonstrated a reduced resistance to Salmonella infection in mice fed diets containing fructo-oligosaccharides (FOS) or xylo-oligosaccharides (XOS). In the present study, faecal and caecal samples from the same mice were analysed in order to study microbial changes potentially explaining the observed effects on the pathogenesis of Salmonella. Denaturing gradient gel electrophoresis revealed that the microbiota in faecal samples from mice fed FOS or XOS were different from faecal samples collected before the feeding trial as well as from faecal profiles generated from control animals. This difference was not seen for caecal profiles. Further analysis of faecal samples by real-time PCR demonstrated a significant increase in the Bacteroidetes phylum, the Bacteroides fragilis group and in Bifidobacterium spp. in mice fed FOS or XOS. The observed bifidogenic effect was more pronounced for XOS than for FOS. The Firmicutes phylum and the Clostridium coccoides group were reduced by both FOS and XOS. Surprisingly, no significant differences were detected between faecal samples collected before and after pathogen challenge in any of the groups. Furthermore, no effect of diets on caecal concentrations of short-chain fatty acids was recorded. In conclusion, diets supplemented with FOS or XOS induced a number of microbial changes in the faecal microbiota of mice. The observed effects of XOS were qualitatively similar to those of FOS, but the most prominent bifidogenic effect was seen for XOS. An increased level of bifidobacteria is thus not in itself preventive against Salmonella infection, since the same XOS or FOS-fed mice were previously reported to be more severely affected by Salmonella than control animals.

Loss of miR-122 expression in liver cancer correlates with suppression of the hepatic phenotype and gain of metastatic properties.

Growing evidence indicates that microRNAs have a significant role in tumor development and may constitute robust biomarkers for cancer diagnosis and prognosis. In this study, we evaluated the clinical and functional relevance of microRNA-122 (miR-122) expression in human hepatocellular carcinoma (HCC). We report that miR-122 is specifically repressed in a subset of primary tumors that are characterized by poor prognosis. We further show that the loss of miR-122 expression in tumor cells segregates with specific gene expression profiles linked to cancer progression, namely the suppression of hepatic phenotype and the acquisition of invasive properties. We identify liver-enriched transcription factors as central regulatory molecules in the gene networks associated with loss of miR-122, and provide evidence suggesting that miR-122 is under the transcriptional control of HNF1A, HNF3A and HNF3B. We further show that loss of miR-122 results in an increase of cell migration and invasion and that restoration of miR-122 reverses this phenotype. In conclusion, miR-122 is a marker of hepatocyte-specific differentiation and an important determinant in the control of cell migration and invasion. From a clinical point of view, our study emphasizes miR-122 as a diagnostic and prognostic marker for HCC progression.

Continuous lactation in dairy cows: effect on milk production and mammary nutrient supply and extraction.

Reports over the past decade have indicated that normal lactational performance can be achieved in genetically superior and high-producing dairy cows, even when the dry period between 2 lactations is omitted. The hypothesis tested in this experiment was that normal lactogenesis I and metabolic function may be achievable in continuously milked high-yielding dairy cows as a result of the genetic selection for lactation performance and hence longevity of mammary epithelial cells. The milk production and mammary nutrient uptake in response to omission of the dry period for cows with an expected peak milk yield higher than 45 kg/d were studied in 28 Holstein dairy cows managed without bovine somatotropin. Performance and metabolic parameters were followed in late gestation and in the following early lactation. Fourteen cows were milked continuously throughout late gestation, and another 14 dairy cows experienced a 7-wk prepartum dry period. Continuous milking during the prepartum period reduced milk production in the following early lactation period by >20%. The reduced milk production could not be readily ascribed to inefficiency of the mechanisms responsible for nutrient uptake by the lactating mammary epithelial cells, nor to systemic endocrine changes. This suggests that lowered mammary nutrient uptake must have been associated with reduced mammary blood flow, metabolic activity, or both, most likely as a result of disturbed lactogenesis I prepartum or lactogenesis II postpartum triggered by as yet unknown local mechanisms. Milk protein content was elevated by 0.4 percentage units in the continuously milked cows. The underlying reason is unknown, but given the current pricing system for milk, it deserves to be further investigated.

Priming the cow for mobilization in the periparturient period: effects of supplementing the dry cow with saturated fat or linseed.

High-producing dairy cows experience negative energy balance in early lactation. Dry-cow feeding management will affect the performance and metabolic status of dairy cows in the following early lactation. The present study evaluates dry-cow feeding strategies for priming lipid metabolism in the dairy cow to overcome the metabolic challenges in the following early lactation. Five weeks before expected calving, 27 cows were assigned to 1 of 3 isonitrogenous and isoenergetic dietary treatments: a low-fat control diet (dry-control); a high saturated fat diet (dry-HSF); and a high linseed diet (dry-HUF). The cows were fed the same TMR lactation diet after calving. The treatments were evaluated by performance and metabolic parameters in blood and liver. The cows fed dry-HSF and dry-HUF had significantly greater plasma nonesterified fatty acid concentrations compared with dry-control, and the dry-HUF cows had the greatest C18:3 concentrations in plasma in the prepartum period. Further, the cows fed dry-HSF and dry-HUF diets had a tendency for the greatest capacity for incomplete beta-oxidation of fatty acids in the liver in wk 3 prepartum. The plasma cholesterol concentration was greatest for cows fed dry-HSF in the prepartum period compared with those fed dry-control and dry-HUF. The cows fed dry-HSF had the lowest plasma nonesterified fatty acid and liver fat concentrations in early lactation compared with the cows fed dry-control and dry-HUF. Data in the literature and the present experiment indicate that supplementing dry cows with a saturated fatty acid source is a positive strategy for priming dairy cows for body fat mobilization in the following early lactation.