The influence of face mask color on perceptions of African American and white men.

Despite their widespread use during the COVID-19 pandemic, face masks hinder abilities to interpret facial expressions. Yet, they can also reduce the appearance of characteristics that are used to categorize individuals into racial groups, such as Afrocentric features. The color of a face mask might also promote associations with certain types of behavior and professional occupations (e.g., blue surgical mask connoting physician stereotypes; black masks potentially being associated with criminality). This study assessed whether the presence and color of a face mask impacted perceptions of a target male of varying race. White participants (N = 250) were presented with an African American or White male adult face from the Chicago Face Database (of equal age and attractiveness) wearing a blue or black surgical mask, or no mask (Photoshopped onto the face) and rated the man on emotions (happy, sad, angry) as well as how trustworthy, threatening, and attractive the target appeared. Targets wearing a blue surgical mask were judged as more trustworthy and attractive than those wearing no mask (perhaps due to association with medical professions), but these judgements were not qualified by race, despite the African American target's selection based on Afrocentric features. The color black on a face mask did not exacerbate negative perceptions of targets, perhaps suggesting a decline effect in previously demonstrated associations between this color and criminal actions. Unlike previous research performed at the beginning of the Covid-19 Pandemic on cloth masks shown to potentially exacerbate racial biases, surgical masks (pleated and made of polymeric materials), appear to lessen potential stereotyping of Black relative to White men.

AAV9 intracerebroventricular gene therapy improves lifespan, locomotor function and pathology in a mouse model of Niemann-Pick type C1 disease.

Niemann-Pick type C disease (NP-C) is a fatal neurodegenerative lysosomal storage disorder. It is caused in 95% of cases by a mutation in the NPC1 gene that encodes NPC1, an integral transmembrane protein localized to the limiting membrane of the lysosome. There is no cure for NP-C but there is a disease-modifying drug (miglustat) that slows disease progression but with associated side effects. Here, we demonstrate in a well-characterized mouse model of NP-C that a single administration of AAV-mediated gene therapy to the brain can significantly extend lifespan, improve quality of life, prevent or ameliorate neurodegeneration, reduce biochemical pathology and normalize or improve various indices of motor function. Over-expression of human NPC1 does not cause adverse effects in the brain and correctly localizes to late endosomal/lysosomal compartments. Furthermore, we directly compare gene therapy to licensed miglustat. Even at a low dose, gene therapy has all the benefits of miglustat but without adverse effects. On the basis of these findings and on-going ascendency of the field, we propose intracerebroventricular gene therapy as a potential therapeutic option for clinical use in NP-C.

Depression in Turner Syndrome: A Systematic Review.

Turner syndrome (TS) is a genetic condition characterized by partial or complete monosomy X. Alterations in hormonal function, height, and peer relationships, among other features and correlates of TS, appear to be risks for depressive illness. In order to summarize what is known about depression in Turner syndrome, with the aim of determining whether individuals with TS are at increased risk for depression, a literature search and analysis were conducted. In total, 69 studies were identified and 35 met criteria of being peer-reviewed English language articles that collected original data on the experience of depression in individuals with TS. Most studies used patient or parent questionnaires to evaluate depressive symptoms. These studies, a majority of which examined adults and half that examined adolescents, found that individuals with TS experienced more frequent and severe depressive symptoms than individuals without TS diagnoses. Articles studying children with TS did not demonstrate a difference in their depressive experience compared to individuals without TS. Three articles used clinician-administered scales, such as the Structured Clinical Interview for DSM-IV; all diagnosed depression in those with TS at higher rates than others. Five studies relied on expert opinion to evaluate depression. The remaining eight articles were case reports or case series that relied on expert opinion. From these data, we conclude that adolescents and adults with TS are at risk for depression and adulthood appears to be the period of the highest risk. Studies in the last 12 years show consistently more severe depressive symptoms in individuals with TS than in previous years. Implications, risk factors, and recommendations for future research are discussed.

Salt-Mediated Au-Cu Nanofoam and Au-Cu-Pd Porous Macrobeam Synthesis.

Multi-metallic and alloy nanomaterials enable a broad range of catalytic applications with high surface area and tuning reaction specificity through the variation of metal composition. The ability to synthesize these materials as three-dimensional nanostructures enables control of surface area, pore size and mass transfer properties, electronic conductivity, and ultimately device integration. Au-Cu nanomaterials offer tunable optical and catalytic properties at reduced material cost. The synthesis methods for Au-Cu nanostructures, especially three-dimensional materials, has been limited. Here, we present Au-Cu nanofoams and Au-Cu-Pd macrobeams synthesized from salt precursors. Salt precursors formed from the precipitation of square planar ions resulted in short- and long-range ordered crystals that, when reduced in solution, form nanofoams or macrobeams that can be dried or pressed into freestanding monoliths or films. Metal composition was determined with X-ray diffraction and energy dispersive X-ray spectroscopy. Nitrogen gas adsorption indicated an Au-Cu nanofoam specific surface area of 19.4 m²/g. Specific capacitance determined with electrochemical impedance spectroscopy was 46.0 F/g and 52.5 F/g for Au-Cu nanofoams and Au-Cu-Pd macrobeams, respectively. The use of salt precursors is envisioned as a synthesis route to numerous metal and multi-metallic nanostructures for catalytic, energy storage, and sensing applications.

Cellulose Nanofiber Biotemplated Palladium Composite Aerogels.

Noble metal aerogels offer a wide range of catalytic applications due to their high surface area and tunable porosity. Control over monolith shape, pore size, and nanofiber diameter is desired in order to optimize electronic conductivity and mechanical integrity for device applications. However, common aerogel synthesis techniques such as solvent mediated aggregation, linker molecules, sol⁻gel, hydrothermal, and carbothermal reduction are limited when using noble metal salts. Here, we present the synthesis of palladium aerogels using carboxymethyl cellulose nanofiber (CNF) biotemplates that provide control over aerogel shape, pore size, and conductivity. Biotemplate hydrogels were formed via covalent cross linking using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) with a diamine linker between carboxymethylated cellulose nanofibers. Biotemplate CNF hydrogels were equilibrated in precursor palladium salt solutions, reduced with sodium borohydride, and rinsed with water followed by ethanol dehydration, and supercritical drying to produce freestanding aerogels. Scanning electron microscopy indicated three-dimensional nanowire structures, and X-ray diffractometry confirmed palladium and palladium hydride phases. Gas adsorption, impedance spectroscopy, and cyclic voltammetry were correlated to determine aerogel surface area. These self-supporting CNF-palladium aerogels demonstrate a simple synthesis scheme to control porosity, electrical conductivity, and mechanical robustness for catalytic, sensing, and energy applications.

1H NMR-Linked Metabolomics Analysis of Liver from a Mouse Model of NP-C1 Disease.

Clinical manifestations of Niemann-Pick type C1 (NP-C1) disease include neonatal hepatosplenomegaly and in some patients progressive liver dysfunction and failure. This study involved a 1H NMR-linked metabolomics analysis of liver samples collected from a NP-C1 disease mutant mouse model in order to explore time-dependent imbalances in metabolic pathways associated with NP-C1 liver dysfunction, including fibrosis. NP-C1 mutant (Npc1-/-; NP-C1), control (Npc1+/+; WT), and NP-C1 heterozygous mice (Npc1+/-; HET) were generated from heterozygote matings. Aqueous extracts of these liver samples collected at time points of 3, 6, 9, and 11 weeks were subjected to high-resolution NMR analysis, and multivariate (MV) metabolomics analyses of data sets acquired were performed. A MV random forests (RFs) model effectively discriminated between NP-C1 and a combined WT/HET hepatic NMR profiles with very high predictive accuracy and reliability. Key distinguishing features included significant upregulations in the hepatic concentrations of phenylalanine, tyrosine, glutamate, lysine/ornithine, valine, threonine, and hypotaurine/methionine, and diminished levels of nicotinate/niacinamide, inosine, phosphoenolpyruvate, and 3-hydroxyphenylacetate. Quantitative pathway topological analysis confirmed that imbalances in tyrosine biosynthesis, and hepatic phenylalanine, tyrosine, glutamate/glutamine, and nicotinate/niacinamide metabolism were involved in the pathogenesis of NP-C1 disease-associated liver dysfunction/damage. 1H NMR-linked metabolomics analysis provides valuable biomarker information regarding hepatic dysfunction or damage in NP-C1 disease.

Suitability of Gelatin Methacrylate and Hydroxyapatite Hydrogels for 3D-Bioprinted Bone Tissue.

BACKGROUND: Complex bone defects are challenging to treat. Autografting is the gold standard for regenerating bone defects; however, its limitations include donor-site morbidity and increased surgical complexity. Advancements in 3D bioprinting (3DBP) offer a promising alternative for viable bone grafts. In this experiment, gels composed of varying levels of gelatin methacrylate (GelMA) and hydroxyapatite (HA) and gelatin concentrations are explored. The objective was to increase the hydroxyapatite content and find the upper limit before the printability was compromised and determine its effect on the mechanical properties and cell viability. METHODS: Design of Experiments (DoE) was used to design 13 hydrogel bioinks of various GelMA/HA concentrations. These bioinks were assessed in terms of their pipettability and equilibrium modulus. An optimal bioink was designed using the DoE data to produce the greatest stiffness while still being pipettable. Three bioinks, one with the DoE-designed maximal stiffness, one with the experimentally defined maximal stiffness, and a literature-based control, were then printed using a 3D bioprinter and assessed for print fidelity. The resulting hydrogels were combined with human bone-marrow-derived mesenchymal stromal cells (hMSCs) and evaluated for cell viability. RESULTS: The DoE ANOVA analysis indicated that the augmented three-level factorial design model used was a good fit (p < 0.0001). Using the model, DoE correctly predicted that a composite hydrogel consisting of 12.3% GelMA, 15.7% HA, and 2% gelatin would produce the maximum equilibrium modulus while still being pipettable. The hydrogel with the most optimal print fidelity was 10% GelMA, 2% HA, and 5% gelatin. There were no significant differences in the cell viability within the hydrogels from day 2 to day 7 (p > 0.05). There was, however, a significantly lower cell viability in the gel composed of 12.3% GelMA, 15.7% HA, and 2% gelatin compared to the other gels with a lower HA concentration (p < 0.05), showing that a higher HA content or print pressure may be cytotoxic within hydrogels. CONCLUSIONS: Extrusion-based 3DBP offers significant advantages for bone-tissue implants due to its high customizability. This study demonstrates that it is possible to create printable bone-like grafts from GelMA and HA with an increased HA content, favorable mechanical properties (145 kPa), and a greater than 80% cell viability.

Real life retrospective study of cannabidiol therapy in alternating hemiplegia of childhood.

BACKGROUND: Many alternating hemiplegia of childhood (AHC) patients have received Cannabidiol (CBD) but, to our knowledge, there are no published data available. GOALS: Test the hypothesis that CBD has favorable effects on AHC spells. METHODS: Retrospective review of available data of AHC patients who received CBD. Primary analysis: Clinical Global Impression Scale of Improvement (CGI-I) score for response of AHC spells to CBD with calculation of 95% confidence interval (CI) for rejection of the null hypothesis. Secondary analyses, performed to achieve an understanding of the effect of CBD as compared to flunarizine, were CGI-I scores of 1) epileptic seizures to CBD, 2) AHC spells to flunarizine, 3) epileptic seizures to flunarizine. Also, Mann-Whitney test was done for comparison of CGI-I scores of CBD and flunarizine to both AHC spells and seizures. RESULTS: We studied 16 AHC patients seen at Duke University and University of Lyon. CI of CGI-I scores for AHC spells in response to CBD and to flunarizine, each separately, indicated a positive response to each of these two medications: neither overlapped with the null hypothesis score, 4, indicating significant positive responses with p < 0.05 for both. These two scores also did not differ (p = 0.84) suggesting similar efficacy of both: CBD score was 2 ± 1.1 with a 95% CI of 1.5-2.6 and flunarizine score was 2.3 ± 1.3 with a 95% CI of 1.7-3.1. In patients who had seizures, CI calculations indicated a positive effect of CBD on seizure CGI scores but not of flunarizine on seizure scores. CBD was well tolerated with no patients discontinuing it due to side effects and with some reporting positive behavioral changes. CONCLUSION: Our study indicates a real-life positive effect of CBD on AHC type spells.

Pathogenic variants associated with speech/cognitive delay and seizures affect genes with expression biases in excitatory neurons and microglia in developing human cortex.

Background & Objective: Congenital brain malformations and neurodevelopmental disorders (NDDs) are common pediatric neurological disorders and result in chronic disability. With the expansion of genetic testing, new etiologies for NDDs are continually uncovered, with as many as one third attributable to single-gene pathogenic variants. While our ability to identify pathogenic variants has continually improved, we have little understanding of the underlying cellular pathophysiology in the nervous system that results from these variants. We therefore integrated phenotypic information from subjects with monogenic diagnoses with two large, single-nucleus RNA-sequencing (snRNAseq) datasets from human cortex across developmental stages in order to investigate cell-specific biases in gene expression associated with distinct neurodevelopmental phenotypes. Methods: Phenotypic data was gathered from 1) a single-institution cohort of 84 neonates with pathogenic single-gene variants referred to Duke Pediatric Genetics, and 2) a cohort of 4,238 patients with neurodevelopmental disorders and pathogenic single-gene variants enrolled in the Deciphering Developmental Disorders (DDD) study. Pathogenic variants were grouped into genesets by neurodevelopmental phenotype and geneset expression across cortical cell subtypes was compared within snRNAseq datasets from 86 human cortex samples spanning the 2nd trimester of gestation to adulthood. Results: We find that pathogenic variants associated with speech/cognitive delay or seizures involve genes that are more highly expressed in cortical excitatory neurons than variants in genes not associated with these phenotypes (Speech/cognitive: p=2.25×10-7; Seizures: p=7.97×10-12). A separate set of primarily rare variants associated with speech/cognitive delay or seizures, distinct from those with excitatory neuron expression biases, demonstrated expression biases in microglia. We also found that variants associated with speech/cognitive delay and an excitatory neuron expression bias could be further parsed by the presence or absence of comorbid seizures. Variants associated with speech/cognitive delay without seizures tended to involve calcium regulatory pathways and showed greater expression in extratelencephalic neurons, while those associated with speech/cognitive delay with seizures tended to involve synaptic regulatory machinery and an intratelencephalic neuron expression bias (ANOVA by geneset p<2×10-16). Conclusions: By combining extensive phenotype datasets from subjects with neurodevelopmental disorders with massive human cortical snRNAseq datasets across developmental stages, we identified cell-specific expression biases for genes in which pathogenic variants are associated with speech/cognitive delay and seizures. The involvement of genes with enriched expression in excitatory neurons or microglia highlights the unique role both cell types play in proper sculpting of the developing brain. Moreover, this information begins to shed light on distinct cortical cell types that are more likely to be impacted by pathogenic variants and that may mediate the symptomatology of resulting neurodevelopmental disorders.

Micronutrient optimization for tissue engineered articular cartilage production of type II collagen.

Tissue Engineering of cartilage has been hampered by the inability of engineered tissue to express native levels of type II collagen in vitro. Inadequate levels of type II collagen are, in part, due to a failure to recapitulate the physiological environment in culture. In this study, we engineered primary rabbit chondrocytes to express a secreted reporter, Gaussia Luciferase, driven by the type II collagen promoter, and applied a Design of Experiments approach to assess chondrogenic differentiation in micronutrient-supplemented medium. Using a Response Surface Model, 240 combinations of micronutrients absent in standard chondrogenic differentiation medium, were screened and assessed for type II collagen promoter-driven Gaussia luciferase expression. While the target of this study was to establish a combination of all micronutrients, alpha-linolenic acid, copper, cobalt, chromium, manganese, molybdenum, vitamins A, E, D and B7 were all found to have a significant effect on type II collagen promoter activity. Five conditions containing all micronutrients predicted to produce the greatest luciferase expression were selected for further study. Validation of these conditions in 3D aggregates identified an optimal condition for type II collagen promoter activity. Engineered cartilage grown in this condition, showed a 170% increase in type II collagen expression (Day 22 Luminescence) and in Young's tensile modulus compared to engineered cartilage in basal media alone.Collagen cross-linking analysis confirmed formation of type II-type II collagen and type II-type IX collagen cross-linked heteropolymeric fibrils, characteristic of mature native cartilage. Combining a Design of Experiments approach and secreted reporter cells in 3D aggregate culture enabled a high-throughput platform that can be used to identify more optimal physiological culture parameters for chondrogenesis.

Recalibration of thinking about adrenocortical function assessment: how the 'random' cortisol relates to the short synacthen test results.

BACKGROUND: The short synacthen test (SST) is the most commonly performed investigation to assess adrenal function. Appropriate criteria for when an SST is performed are subject to debate. We investigated how random serum cortisol levels relate to SST response. METHODS: We examined random cortisol measurements taken between 04.40-23.55 p.m. results of SST baseline and 30-/60-min cortisol performed over 12 months (225 SSTs) at Salford Royal Hospital. Serum cortisol was measured on the Siemens Centaur Analyser.A 30-60-min cortisol concentration of ≥450 nmol/L defined a pass; 350-449 nmol/L defined borderline. RESULTS: Patients only proceeded to SST if random cortisol was <400 nmol/L. For those not on corticosteroids for at least 2 weeks, 42/43 (97.7%) cases with random cortisol concentration of ≥200 nmol/L had an SST 'pass'. The relation was less clear with corticosteroid treatment (19/35 cases; 54%).For those not taking glucocorticoid treatment (including inhaled/topical corticosteroids) in the previous 2 weeks, 91.8% of SSTs were pass/2.7% borderline/5.5% fail. For those on steroids, 51.9% of SSTs were a pass/11.4% were borderline.In relation to the postsynacthen cortisol pass cut-off of ≥450 nmol/L, in 15/207 (7.2%) of cases, the 60-min cortisol was ≥450 nmol/L (adequate adrenocortical function), but 30-min cortisol was below this. In all cases where the 30-min cortisol did indicate a pass (i.e. was ≥450 nmol/L) the 60-min cortisol was also ≥450 nmol/L. CONCLUSION: Our findings suggest that if the random cortisol level is ≥200 nmol/L, regardless of the time of day and the person was not taking corticosteroid treatment in the previous 2 weeks, SST may not be needed. Our data also suggests that 60-min cortisol retains utility.

Acetyl-leucine slows disease progression in lysosomal storage disorders.

Acetyl-dl-leucine is a derivative of the branched chain amino acid leucine. In observational clinical studies, acetyl-dl-leucine improved symptoms of ataxia, in particular in patients with the lysosomal storage disorder, Niemann-Pick disease type C1. Here, we investigated acetyl-dl-leucine and its enantiomers acetyl-l-leucine and acetyl-d-leucine in symptomatic Npc1-/- mice and observed improvement in ataxia with both individual enantiomers and acetyl-dl-leucine. When acetyl-dl-leucine and acetyl-l-leucine were administered pre-symptomatically to Npc1-/- mice, both treatments delayed disease progression and extended life span, whereas acetyl-d-leucine did not. These data are consistent with acetyl-l-leucine being the neuroprotective enantiomer. Altered glucose and antioxidant metabolism were implicated as one of the potential mechanisms of action of the l-enantiomer in Npc1-/- mice. When the standard of care drug miglustat and acetyl-dl-leucine were used in combination significant synergy resulted. In agreement with these pre-clinical data, when Niemann-Pick disease type C1 patients were evaluated after 12 months of acetyl-dl-leucine treatment, rates of disease progression were slowed, with stabilization or improvement in multiple neurological domains. A beneficial effect of acetyl-dl-leucine on gait was also observed in this study in a mouse model of GM2 gangliosidosis (Sandhoff disease) and in Tay-Sachs and Sandhoff disease patients in individual-cases of off-label-use. Taken together, we have identified an unanticipated neuroprotective effect of acetyl-l-leucine and underlying mechanisms of action in lysosomal storage diseases, supporting its further evaluation in clinical trials in lysosomal disorders.

Defective platelet function in Niemann-Pick disease type C1.

Niemann-Pick disease type C (NPC) is a neurodegenerative lysosomal storage disorder caused by mutations in either NPC1 (95% of cases) or NPC2. Reduced late endosome/lysosome calcium (Ca2+) levels and the accumulation of unesterified cholesterol and sphingolipids within the late endocytic system characterize this disease. We previously reported impaired lysosome-related organelle (LRO) function in Npc1 -/- Natural Killer cells; however, the potential contribution of impaired acid compartment Ca2+ flux and LRO function in other cell types has not been determined. Here, we investigated LRO function in NPC1 disease platelets. We found elevated numbers of circulating platelets, impaired platelet aggregation and prolonged bleeding times in a murine model of NPC1 disease. Electron microscopy revealed abnormal ultrastructure in murine platelets, consistent with that seen in a U18666A (pharmacological inhibitor of NPC1) treated megakaryocyte cell line (MEG-01) exhibiting lipid storage and acidic compartment Ca2+ flux defects. Furthermore, platelets from NPC1 patients across different ages were found to cluster at the lower end of the normal range when platelet numbers were measured and had platelet volumes that were clustered at the top of the normal range. Taken together, these findings highlight the role of acid compartment Ca2+ flux in the function of platelet LROs.

Synthesis Method for Cellulose Nanofiber Biotemplated Palladium Composite Aerogels.

Here, a method to synthesize cellulose nanofiber biotemplated palladium composite aerogels is presented. Noble metal aerogel synthesis methods often result in fragile aerogels with poor shape control. The use of carboxymethylated cellulose nanofibers (CNFs) to form a covalently bonded hydrogel allows for the reduction of metal ions such as palladium on the CNFs with control over both nanostructure and macroscopic aerogel monolith shape after supercritical drying. Crosslinking the carboxymethylated cellulose nanofibers is achieved using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) in the presence of ethylenediamine. The CNF hydrogels maintain their shape throughout synthesis steps including covalent crosslinking, equilibration with precursor ions, metal reduction with high concentration reducing agent, rinsing in water, ethanol solvent exchange, and CO2 supercritical drying. Varying the precursor palladium ion concentration allows for control over the metal content in the final aerogel composite through a direct ion chemical reduction rather than relying on the relatively slow coalescence of pre-formed nanoparticles used in other sol-gel techniques. With diffusion as the basis to introduce and remove chemical species into and out of the hydrogel, this method is suitable for smaller bulk geometries and thin films. Characterization of the cellulose nanofiber-palladium composite aerogels with scanning electron microscopy, X-ray diffractometry, thermal gravimetric analysis, nitrogen gas adsorption, electrochemical impedance spectroscopy, and cyclic voltammetry indicates a high surface area, metallized palladium porous structure.

A Rapid Synthesis Method for Au, Pd, and Pt Aerogels Via Direct Solution-Based Reduction.

Here, a method to synthesize gold, palladium, and platinum aerogels via a rapid, direct solution-based reduction is presented. The combination of various precursor noble metal ions with reducing agents in a 1:1 (v/v) ratio results in the formation of metal gels within seconds to minutes compared to much longer synthesis times for other techniques such as sol-gel. Conducting the reduction step in a microcentrifuge tube or small volume conical tube facilitates a proposed nucleation, growth, densification, fusion, equilibration model for gel formation, with final gel geometry smaller than the initial reaction volume. This method takes advantage of the vigorous hydrogen gas evolution as a by-product of the reduction step, and as a consequence of reagent concentrations. The solvent accessible specific surface area is determined with both electrochemical impedance spectroscopy and cyclic voltammetry. After rinsing and freeze drying, the resulting aerogel structure is examined with scanning electron microscopy, X-ray diffractometry, and nitrogen gas adsorption. The synthesis method and characterization techniques result in a close correspondence of aerogel ligament sizes. This synthesis method for noble metal aerogels demonstrates that high specific surface area monoliths may be achieved with a rapid and direct reduction approach.

Nutrition in Pregnancy Following Bariatric Surgery.

The widespread use of bariatric surgery for the treatment of morbid obesity has led to a dramatic increase in the numbers of women who become pregnant post-surgery. This can present new challenges, including a higher risk of protein and calorie malnutrition and micronutrient deficiencies in pregnancy due to increased maternal and fetal demand. We undertook a focused, narrative review of the literature and present pragmatic recommendations. It is advisable to delay pregnancy for at least 12 months following bariatric surgery. Comprehensive pre-conception and antenatal care is essential to achieving the best outcomes. Nutrition in pregnancy following bariatric surgery requires specialist monitoring and management. A multidisciplinary approach to care is desirable with close monitoring for deficiencies at each trimester.

Differential response of the liver to bile acid treatment in a mouse model of Niemann-Pick disease type C.

Niemann-Pick disease type C (NPC) disease is a neurodegenerative lysosomal storage disease caused by mutations in the NPC1 or NPC2 genes. Liver disease is also a common feature of NPC that can present as cholestatic jaundice in the neonatal period. Liver enzymes can remain elevated above the normal range in some patients as they age. We recently reported suppression of the P450 detoxification system in a mouse model of NPC disease and in post-mortem liver from NPC patients. As bile acids regulate the P450 system, we tested bile acid treatment using ursodeoxycholic acid (UDCA; 3α, 7ß-dihydroxy-5ß-cholanic acid), a hydrophilic bile acid, which is used to treat several cholestatic disorders. In this study, we compared UDCA treatment with the bile acid cholic acid (CA), and found unexpected hepatotoxicity in response to CA in Npc1 mice, but not to UDCA, suggesting that only UDCA should be used as an adjunctive therapy in NPC patients.