Effects of Preoperative Virtual Reality Magnetic Resonance Imaging on Preoperative Anxiety in Patients Undergoing Arthroscopic Knee Surgery: A Randomized Controlled Study.

PURPOSE: To assess the effect of a preoperative virtual reality (VR) experience of 3-dimensional (3D) reconstructed magnetic resonance images (MRIs) on anxiety reduction in patients undergoing arthroscopic knee surgery. METHODS: Patients in the VR group watched a 3D model of their own MRI through a VR headset describing the anatomy of the knee as well as their own lesion of interest for an arthroscopic procedure. Patients in the non-VR (NR) group received standard preoperative information about their MRI. The primary outcome for analysis was the Amsterdam Preoperative Anxiety and Information Scale score to measure level of anxiety and the need for information in patients undergoing arthroscopic knee surgery. Secondary outcomes were rated with visual analog scale (VAS) scores measuring patient pain, preparedness, satisfaction, and stress. RESULTS: Regarding the Amsterdam Preoperative Anxiety and Information Scale score, the sum S (surgery-related anxiety) and sum C (combined anxiety component) subscales showed significantly better outcomes in the VR group (median [interquartile range] for sum S = 2.0 [2.0-4.0], median [quartile 1-quartile 3] sum C = 4.0 [4.0-8.5]) than in the NR group (median [interquartile range] for sum S = 4.9 [3.0-5.0], median [quartile 1-quartile 3] sum C = 8.0 [5.3-9.8]) (P = .014 and P = .005, respectively). Regarding VAS scores, preoperative measures showed significantly better outcomes in satisfaction among VR group patients (95 [90.0-100.0]) in comparison to NR group patients (85 [70.0-96.0]) (P = .010). For postoperative VAS measures, the VR group (satisfaction score = 95 [90.0-100.0], stress score = 15 [2.5-37.5]) showed significantly better outcomes in satisfaction and stress in comparison to the NR group (satisfaction score = 85 [70.0-97.5], stress score = 30 [30.0-50.0]). CONCLUSIONS: Application of preoperative VR experience of 3D reconstructed knee MRIs in patients undergoing arthroscopic knee surgery reduces anxiety around surgical encounters. The VR patient group was more satisfied overall and less stressed postoperatively. However, perioperative pain and preparedness were not affected by VR exposure. LEVEL OF EVIDENCE: Level I, randomized controlled trial.

Development of novel on-line capillary gas chromatography-based analysis method for volatile organic compounds produced by aerobic fermentation.

Many volatile compounds, such as isoprene, a precursor used in the synthesis of natural rubber, have been produced through fermentation using genetically engineered microorganisms. Despite this biotechnological success, measuring the concentrations of volatile compounds during fermentation is difficult because of their high volatility. In current systems, off-line analytical methods usually lead to product loss, whereas on-line methods raise the production cost due to the requirement of complex devices. Here, we developed a novel on-line gas chromatography (GC)-based system for analyzing the concentration of isoprene with the aim to minimize the cost and requirement for devices as compared to current strategies. In this system, a programmable logic controller is used to combine conventional GC with a syringe pump module (SPM) directly connected to the exhaust pipe of the fermentor, and isoprene-containing samples are continuously pumped from the SPM into the GC using an air cylinder recycle stream. We showed that this novel system enables isoprene analysis during fermentation with convenient equipment and without the requirement of an expensive desorption tube. Furthermore, this system may be extended to the detection of other volatile organic compounds in fermentation or chemical processes.

Enhancement of L-Threonine Production by Controlling Sequential Carbon-Nitrogen Ratios during Fermentation.

Controlling the residual glucose concentration is important for improving productivity in L-threonine fermentation. In this study, we developed a procedure to automatically control the feeding quantity of glucose solution as a function of ammonia-water consumption rate. The feeding ratio (RC/N) of glucose and ammonia water was predetermined via a stoichiometric approach, on the basis of glucose-ammonia water consumption rates. In a 5-L fermenter, 102 g/l L-threonine was obtained using our glucose-ammonia water combined feeding strategy, which was then successfully applied in a 500-L fermenter (89 g/l). Therefore, we conclude that an automatic combination feeding strategy is suitable for improving L-threonine production.

Reduction of Adipose Tissue Mass by the Angiogenesis Inhibitor ALS-L1023 from Melissa officinalis.

It has been suggested that angiogenesis modulates adipogenesis and obesity. This study was undertaken to determine whether ALS-L1023 (ALS) prepared by a two-step organic solvent fractionation from Melissa leaves, which exhibits antiangiogenic activity, can regulate adipose tissue growth. The effects of ALS on angiogenesis and extracellular matrix remodeling were measured using in vitro assays. The effects of ALS on adipose tissue growth were investigated in high fat diet-induced obese mice. ALS inhibited VEGF- and bFGF-induced endothelial cell proliferation and suppressed matrix metalloproteinase (MMP) activity in vitro. Compared to obese control mice, administration of ALS to obese mice reduced body weight gain, adipose tissue mass and adipocyte size without affecting appetite. ALS treatment decreased blood vessel density and MMP activity in adipose tissues. ALS reduced the mRNA levels of angiogenic factors (VEGF-A and FGF-2) and MMPs (MMP-2 and MMP-9), whereas ALS increased the mRNA levels of angiogenic inhibitors (TSP-1, TIMP-1, and TIMP-2) in adipose tissues. The protein levels of VEGF, MMP-2 and MMP-9 were also decreased by ALS in adipose tissue. Metabolic changes in plasma lipids, liver triglycerides, and hepatic expression of fatty acid oxidation genes occurred during ALS-induced weight loss. These results suggest that ALS, which has antiangiogenic and MMP inhibitory activities, reduces adipose tissue mass in nutritionally obese mice, demonstrating that adipose tissue growth can be regulated by angiogenesis inhibitors.

Ovarian-sparing local mass excision for ovarian fibroma/fibrothecoma in premenopausal women.

OBJECTIVES: To evaluate the recurrence rate of ovarian fibroma/fibrothecoma and reproductive outcomes following ovarian-sparing local mass excision in premenopausal women. STUDY DESIGN: A retrospective cohort study was performed at two gynecologic surgery centers using data collected between January 2005 and December 2011. It included premenopausal patients treated with ovarian-sparing local mass excision and pathologically proven ovarian fibroma/fibrothecoma who were followed up for at least 6 months. The recurrence of fibroma/fibrothecoma and pregnancy outcomes in those who wanted to conceive after local mass excision were collected and analyzed. RESULTS: The mean age of the patients (n=50) was 33.3±6.9 years (range, 20-50 years), and the mean follow-up duration was 26.6±19.2 months (range, 6-88 months). Fibroma was present in 40 patients, fibrothecoma in 7, and cellular fibroma in 3. Natural conception occurred in 11 of the 12 patients who became pregnant during the follow-up period. On follow-up ultrasonography, one patient experienced recurrent disease, 50 months after initial surgery, resulting in a crude overall recurrence rate of only 2%. CONCLUSION: Given the 2% recurrence rate of ovarian fibroma/fibrothecoma following ovarian sparing local mass excision, local mass excision appears to be an effective surgical option in women of reproductive age.

Anti-inflammatory effect of methylpenicinoline from a marine isolate of Penicillium sp. (SF-5995): inhibition of NF-κB and MAPK pathways in lipopolysaccharide-induced RAW264.7 macrophages and BV2 microglia.

In the course of a search for anti-inflammatory metabolites from marine-derived fungi, methylpenicinoline (1) was isolated from a marine isolate of Penicillin sp. Compound 1 inhibited lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production by suppressing the expression of inducible NO synthase (iNOS) in RAW264.7 macrophages and BV2 microglia. It also attenuated prostaglandin E2 (PGE2) production by suppressing cyclooxygenase-2 (COX-2) expression in a concentration-dependent manner (from 10 µM to 80 µM) without affecting cell viability. In addition, compound 1 reduced the production of the pro-inflammatory cytokine interleukin-1ß (IL-1ß). In a further study designed to elucidate the mechanism of its anti-inflammatory effects, compound 1 was shown to block nuclear factor-kappa B (NF-κB) activation in LPS-induced RAW264.7 macrophages and BV2 microglia by inhibiting the phosphorylation of inhibitor kappa B-α (IκB-α), thereby suppressing the nuclear translocation of NF-κB dimers, namely p50 and p65, that are known to be crucial molecules associated with iNOS and COX-2 expression. In addition, compound 1 inhibited the activation of mitogen-activated protein kinase (MAPK) pathways. Taken together, the results suggest that compound 1 might be a valuable therapeutic agent for the treatment of anti-inflammatory and anti-neuroinflammatory diseases.

Genetics of low spinal muscular atrophy carrier frequency in sub-Saharan Africa.

OBJECTIVE: Spinal muscular atrophy (SMA) is one of the most common severe hereditary diseases of infancy and early childhood in North America, Europe, and Asia. SMA is usually caused by deletions of the survival motor neuron 1 (SMN1) gene. A closely related gene, SMN2, modifies the disease severity. SMA carriers have only 1 copy of SMN1 and are relatively common (1 in 30-50) in populations of European and Asian descent. SMN copy numbers and SMA carrier frequencies have not been reliably estimated in Malians and other sub-Saharan Africans. METHODS: We used a quantitative polymerase chain reaction assay to determine SMN1 and SMN2 copy numbers in 628 Malians, 120 Nigerians, and 120 Kenyans. We also explored possible mechanisms for SMN1 and SMN2 copy number differences in Malians, and investigated their effects on SMN mRNA and protein levels. RESULTS: The SMA carrier frequency in Malians is 1 in 209, lower than in Eurasians. Malians and other sub-Saharan Africans are more likely to have ≥3 copies of SMN1 than Eurasians, and more likely to lack SMN2 than Europeans. There was no evidence of gene conversion, gene locus duplication, or natural selection from malaria resistance to account for the higher SMN1 copy numbers in Malians. High SMN1 copy numbers were not associated with increased SMN mRNA or protein levels in human cell lines. INTERPRETATION: SMA carrier frequencies are much lower in sub-Saharan Africans than in Eurasians. This finding is important to consider in SMA genetic counseling in individuals with black African ancestry.

Clinical characteristics and surgical management options for ovarian fibroma/fibrothecoma: a study of 97 cases.

AIMS: The aims of this study were to analyze the clinical characteristics, diagnostic features, and operative outcomes of patients with ovarian fibroma/fibrothecoma and to discuss appropriate management options. METHODS: We performed a retrospective comparative analysis of 97 patients with ovarian fibroma/fibrothecoma who underwent laparoscopic and laparotomic procedures, including tumorectomy between January 2008 and December 2011. RESULTS: The mean patient age was 42.5 ± 11.4 years. Seventy-three patients (75.3%) were premenopausal women. A preoperative diagnosis of benign ovarian tumor or fibroma was made in only 49 cases (50.5%). We found that 42.2% of cases were misdiagnosed as uterine myomas (n = 41) and 6.2% were misdiagnosed as malignant ovarian tumors (n = 6). The presence of ascites was associated with larger tumor size (p < 0.05) but not higher CA125 levels (p = 0.159). Twenty-nine patients (29.9%) underwent laparotomy, and 68 (70.1%), laparoscopic surgery. Laparoscopic surgery facilitated shorter operation times than laparotomy (p < 0.05). Tumorectomy was performed in 40 patients (43.5%), 36 (90%) of whom underwent laparoscopy with operative outcomes comparable to those of patients who underwent laparotomy. CONCLUSIONS: Ovarian fibromas/fibrothecomas are often misdiagnosed as uterine myomas and malignant ovarian tumors. Laparoscopic surgery including tumorectomy may be an effective surgical approach in patients with ovarian fibromas/fibrothecomas.

Clinical and myopathological characteristics of desminopathy caused by a mutation in desmin tail domain.

BACKGROUND: Most of the previously described pathogenic mutations in desmin are located in highly conserved α-helical domains that play an important role in intermediate filament assembly. The role of the C-terminus non-α-helical 'tail' domain is much less investigated and until recently mutations in this domain have been implicated in only a few patients. The majority of reported desminopathy cases caused by the tail mutations were sporadic, creating a representation bias regarding the disease frequency and phenotypic characteristics. METHODS: We performed detailed genotype-phenotype analysis of autosomal dominant desminopathy associated with tail domain mutations in a four-generation autosomal dominant family with 16 members affected by a progressive cardiac and/or skeletal myopathy caused by a c.1346A>C (p.Lys449Thr) mutation located in the tail domain of desmin. RESULTS: Phenotypic features in patients with tail domain mutations are similar to those in patients with mutations localized in the 1B and 2B α-helical domains. CONCLUSION: We recommend that the tail domain is searched for mutations as intensely as desmin coil domains which until recently were considered to be more 'functional'.

Laparoendoscopic single-site surgery (LESS) versus conventional laparoscopic surgery for adnexal preservation: a randomized controlled study.

OBJECTIVE: To compare the operative outcomes, postoperative pain, and subsequent convalescence after laparoendoscopic single-site surgery (LESS) or conventional laparoscopic surgery for adnexal preservation. STUDY DESIGN: From December 2009 to September 2010, 63 patients underwent LESS (n = 33) or a conventional laparoscopic surgery (n = 30) for cyst enucleation. The overall operative outcomes including postoperative pain measurement using the visual analog scale (VAS) were evaluated (time points 6, 24, and 24 hours). The convalescence data included data obtained from questionnaires on the need for analgesics and on patient-reported time to recovery end points. RESULTS: The preoperative characteristics did not significantly differ between the two groups. The postoperative hemoglobin drop was higher in the LESS group than in the conventional laparoscopic surgery group (P = 0.048). Postoperative pain at each VAS time point, oral analgesic requirement, intramuscular analgesic requirement, and the number of days until return to work were similar in both groups. CONCLUSION: In adnexa-preserving surgery performed in reproductive-age women, the operative outcomes, including satisfaction of the patients and convalescence after surgery, are comparable for LESS and conventional laparoscopy. LESS may be a feasible and a promising alternative method for scarless abdominal surgery in the treatment of young women with adnexal cysts.

Identical de novo mutation in the type 1 ryanodine receptor gene associated with fatal, stress-induced malignant hyperthermia in two unrelated families.

BACKGROUND: Mutations in the type 1 ryanodine receptor gene (RYR1) result in malignant hyperthermia, a pharmacogenetic disorder typically triggered by administration of anesthetics. However, cases of sudden death during exertion, heat challenge, and febrile illness in the absence of triggering drugs have been reported. The underlying causes of such drug-free fatal "awake" episodes are unknown. METHODS: De novo R3983C variant in RYR1 was identified in two unrelated children who experienced fatal, nonanesthetic awake episodes associated with febrile illness and heat stress. One of the children also had a second novel, maternally inherited D4505H variant located on a separate haplotype. Effects of all possible heterotypic expression conditions on RYR1 sensitivity to caffeine-induced Ca release were determined in expressing RYR1-null myotubes. RESULTS: Compared with wild-type RYR1 alone (EC50 = 2.85 ± 0.49 mM), average (± SEM) caffeine sensitivity of Ca release was modestly increased after coexpression with either R3983C (EC50 = 2.00 ± 0.39 mM) or D4505H (EC50 = 1.64 ± 0.24 mM). Remarkably, coexpression of wild-type RYR1 with the double mutant in cis (R3983C-D4505H) produced a significantly stronger sensitization of caffeine-induced Ca release (EC50 = 0.64 ± 0.17 mM) compared with that observed after coexpression of the two variants on separate subunits (EC50 = 1.53 ± 0.18 mM). CONCLUSIONS: The R3983C mutation potentiates D4505H-mediated sensitization of caffeine-induced RYR1 Ca release when the mutations are in cis (on the same subunit) but not when present on separate subunits. Nevertheless, coexpression of the two variants on separate subunits still resulted in a ∼2-fold increase in caffeine sensitivity, consistent with the observed awake episodes and heat sensitivity.

Clinical and myopathological evaluation of early- and late-onset subtypes of myofibrillar myopathy.

Myofibrillar myopathies (MFM) are a group of disorders associated with mutations in DES, CRYAB, MYOT, ZASP, FLNC, or BAG3 genes and characterized by disintegration of myofibrils and accumulation of degradation products into intracellular inclusions. We retrospectively evaluated 53 MFM patients from 35 Spanish families. Studies included neurologic exam, muscle imaging, light and electron microscopic analysis of muscle biopsy, respiratory function testing and cardiologic work-up. Search for pathogenic mutations was accomplished by sequencing of coding regions of the six genes known to cause MFM. Mutations in MYOT were the predominant cause of MFM in Spain affecting 18 of 35 families, followed by DES in 11 and ZASP in 3; in 3 families the cause of MFM remains undetermined. Comparative analysis of DES, MYOT and ZASP associated phenotypes demonstrates substantial phenotypic distinctions that should be considered in studies of disease pathogenesis, for optimization of subtype-specific treatments and management, and directing molecular analysis.

Survival of prototype strains of somatic coliphage families in environmental waters and when exposed to UV low-pressure monochromatic radiation or heat.

The potential use of specific somatic coliphage taxonomic groups as viral indicators based on their persistence and prevalence in water was investigated. Representative type strains of the 4 major somatic coliphage taxonomic groups were seeded into reagent water and an ambient surface water source of drinking water and the survival of the added phages was measured over 90 days at temperatures of 23-25 and 4 °C. Microviridae (type strain PhiX174), Siphoviridae (type strain Lambda), and Myoviridae (type strain T4) viruses were the most persistent in water at the temperatures tested. The Microviridae (type strain PhiX174) and the Siphoviridae (type strain Lambda) were the most resistant viruses to UV radiation and the Myoviridae (type strain T4) and the Microviridae (type strain PhiX174) were the most resistant viruses to heat. Based on their greater persistence in water over time and their relative resistance to heat and/or UV radiation, the Myoviridae (type strain T4), the Microviridae (type strain PhiX174), and the Siphoviridae (type strain Lambda) were the preferred candidate somatic coliphages as fecal indicator viruses in water, with the Microviridae (type strain PhiX174) the most resistant to these conditions overall.

Signet ring cell carcinoma arising from a solitary juvenile polyp in the colon.

Juvenile polyps are relatively common polyps that affect predominantly young patients and may occur in isolated, multiple, and/or familial forms. They have been considered to be benign lesions without neoplastic potential, but for patients with multiple juvenile polyposis, the cumulative malignant risk is greater than fifty percents. In patients with a solitary polyp, the risks are minimal, and only a few cases of malignant change from a solitary juvenile polyp have been reported. We describe the case of a twenty one year old female with one solitary juvenile polyp, which contained a signet ring cell carcinoma in the mucosal layer.

Nemaline myopathy type 6: clinical and myopathological features.

Nemaline myopathy (NEM) is one of the most common congenital myopathies. A unique subtype, NEM6, maps to chromosome 15q21-q23 in two pedigrees, but the causative gene has not been determined. We conducted clinical examination and myopathological studies in a new NEM family. Genotyping and gene screening were accomplished by searching known and 18 new candidate genes. The disease started in childhood by affecting proximal and distal muscles and causing slowness of movements. Muscle biopsies showed numerous nemaline rods and core-like formations. Suggestive linkage to chromosome 15q22-q23 was established. Genes known to be mutated in NEM or core-rod myopathy were screened and excluded. No pathogenic mutations were identified in other candidate genes. The disease in this Spanish family was classified as NEM6. It is phenotypically similar and probably allelic to the two previously reported NEM6 pedigrees. Further studies of these families will lead to the identification of the NEM6 gene.

Inheritance patterns and phenotypic features of myofibrillar myopathy associated with a BAG3 mutation.

Myofibrillar myopathies are a heterogeneous group of neuromuscular disorders characterized by disintegration of myofibrils. The inheritance pattern is commonly autosomal dominant, but there has been a striking absence of secondary cases noted in a BAG3-associated subtype. We studied three families with BAG3 p.Pro209Leu mutation showing a severe phenotype of myofibrillar myopathy and axonal neuropathy with giant axons. In one family, transmission to a pair of siblings has occurred from their asymptomatic father who showed somatic mosaicism. In two other families, neither of the parents was affected or showed detectable level of somatic mosaicism. These observations suggest that the BAG3 variant of myofibrillar myopathy may result from a spontaneous mutation at an early point of embryonic development and that transmission from a mosaic parent may occur more than once. The study underlines the importance of parental evaluation as it may have implications for genetic counseling.

Epidemiology of Viliuisk encephalomyelitis in Eastern Siberia.

BACKGROUND: Viliuisk encephalomyelitis is a disorder that starts, in most cases, as an acute meningoencephalitis. Survivors of the acute phase develop a slowly progressing neurologic syndrome characterized by dementia, dysarthria, and spasticity. An epidemic of this disease has been spreading throughout the Yakut Republic of the Russian Federation. Although clinical, neuropathologic, and epidemiologic data suggest infectious etiology, multiple attempts at pathogen isolation have been unsuccessful. METHODS: Detailed clinical, pathologic, laboratory, and epidemiologic studies have identified 414 patients with definite Viliuisk encephalomyelitis in 15 of 33 administrative regions of the Yakut Republic between 1940 and 1999. All data are documented in a Registry. RESULTS: The average annual Viliuisk encephalomyelitis incidence rate at the height of the epidemic reached 8.8 per 100,000 population and affected predominantly young adults. The initial outbreak occurred in a remote isolated area of the middle reaches of Viliui River; the disease spread to adjacent areas and further in the direction of more densely populated regions. The results suggest that intensified human migration from endemic villages led to the emergence of this disease in new communities. Recent social and demographic changes have presumably contributed to a subsequent decline in disease incidence. CONCLUSIONS: Based on the largest known set of diagnostically verified Viliuisk encephalomyelitis cases, we demonstrate how a previously little-known disease that was endemic in a small indigenous population subsequently reached densely populated areas and produced an epidemic involving hundreds of persons.

Viliuisk encephalomyelitis in Eastern Siberia - analysis of 390 cases.

Viliuisk encephalomyelitis (VE) is a unique disease occurring in the Yakut (Sakha) population of Eastern Siberia. VE is always fatal, with some patients dying during the acute encephalitic phase of illness; those surviving the acute phase develop progressive dementia, rigidity and spastic quadriparesis as part of a more prolonged pan-encephalitic syndrome. The disease is characterized neuropathologically by multiple widespread micronecrotic foci with marked inflammatory reactions and subsequent gliosis throughout the cerebral cortex, basal ganglia, cerebellum and brain stem. The acute febrile onset with cerebrospinal fluid pleocytosis and increased protein and neuropathology showing inflammatory reactions suggest that VE is an infectious disease, but the causative agent has not been identified. Initially detected in a small mixed Yakut-Evenk population of the mid-Viliui region, the disease subsequently spread south to densely populated areas around the capital city of Yakutsk. The occurrence of secondary VE cases in households and the introduction of the disease by migrants into new populations indicate that the disease is horizontally transmitted in a setting of a long intra-household contact. Although there has been a recent decline in the number of cases, increasing travel may result in further spread of this fatal disease to susceptible individuals in other regions of the world.

In-frame deletion in the seventh immunoglobulin-like repeat of filamin C in a family with myofibrillar myopathy.

Myofibrillar myopathies (MFMs) are an expanding and increasingly recognized group of neuromuscular disorders caused by mutations in DES, CRYAB, MYOT, and ZASP. The latest gene to be associated with MFM was FLNC; a p.W2710X mutation in the 24th immunoglobulin-like repeat of filamin C was shown to be the cause of a distinct type of MFM in several German families. We studied an International cohort of 46 patients from 39 families with clinically and myopathologically confirmed MFM, in which DES, CRYAB, MYOT, and ZASP mutations have been excluded. In patients from an unrelated family a 12-nucleotide deletion (c.2997_3008del) in FLNC resulting in a predicted in-frame four-residue deletion (p.Val930_Thr933del) in the seventh repeat of filamin C was identified. Both affected family members, mother and daughter, but not unrelated control individuals, carried the p.Val930_Thr933del mutation. The mutation is transcribed and, based on myopathological features and immunoblot analysis, it leads to an accumulation of dysfunctional filamin C in the myocytes. The study results suggest that the novel p.Val930_Thr933del mutation in filamin C is the cause of MFM but also indicate that filamin C mutations are a comparatively rare cause of MFM.

Regulation of obesity and lipid disorders by herbal extracts from Morus alba, Melissa officinalis, and Artemisia capillaris in high-fat diet-induced obese mice.

Melissa officinalis L. (Labiatae), Morus alba L. (Moraceae), and Artemisia capillaris Thunb. (Compositae) are suggested to be involved in the regulation of hyperlipidemia. We hypothesized that Ob-X, a mixture of three herbs, Morus alba, Melissa officinalis and Artemisia capillaris [corrected] improves lipid metabolism, body weight gain and adiposity and that peroxisome proliferator-activated receptor alpha (PPARalpha) is associated with these events. Mice fed a high-fat diet for 12 weeks exhibited increases in body weight gain and adipose tissue mass compared with mice fed a low fat diet. However, feeding a high-fat diet supplemented with Ob-X significantly reduced these effects. Ob-X treatment also decreased the circulating levels of triglycerides and total cholesterol, and inhibited hepatic lipid accumulation. Ob-X supplementation was found to increase the hepatic mRNA levels of PPARalpha target enzymes responsible for fatty acid beta-oxidation. Moreover, Ob-X elevated the endogenous expression of a luciferase reporter gene containing three copies of a PPAR response element (PPRE) in NMu2Li liver cells. These data demonstrate that Ob-X regulates body weight gain, adipose tissue mass, and lipid metabolism in part through changes in the expression of hepatic PPARalpha target genes.