The tocopherol transfer protein mediates vitamin E trafficking between cerebellar astrocytes and neurons.

Alpha-tocopherol (vitamin E) is an essential nutrient that functions as a major lipid-soluble antioxidant in humans. The alpha-tocopherol transfer protein (TTP) binds α-tocopherol with high affinity and selectivity and regulates whole-body distribution of the vitamin. Heritable mutations in the TTPA gene result in familial vitamin E deficiency, elevated indices of oxidative stress, and progressive neurodegeneration that manifest primarily in spinocerebellar ataxia. Although the essential role of vitamin E in neurological health has been recognized for over 50 years, the mechanisms by which this essential nutrient is transported in the central nervous system are poorly understood. Here we found that, in the murine cerebellum, TTP is selectively expressed in glial fibrillary acidic protein-positive astrocytes, where it facilitates efflux of vitamin E to neighboring neurons. We also show that induction of oxidative stress enhances the transcription of the TtpA gene in cultured cerebellar astrocytes. Furthermore, secretion of vitamin E from astrocytes is mediated by an ABC-type transporter, and uptake of the vitamin into neurons involves the low-density lipoprotein receptor-related protein 1. Taken together, our data indicate that TTP-expressing astrocytes control the delivery of vitamin E from astrocytes to neurons, and that this process is homeostatically responsive to oxidative stress. These are the first observations that address the detailed molecular mechanisms of vitamin E transport in the central nervous system, and these results have important implications for understanding the molecular underpinnings of oxidative stress-related neurodegenerative diseases.

The rare C9 P167S risk variant for age-related macular degeneration increases polymerization of the terminal component of the complement cascade.

Age-related macular degeneration (AMD) is a complex neurodegenerative eye disease with behavioral and genetic etiology and is the leading cause of irreversible vision loss among elderly Caucasians. Functionally significant genetic variants in the alternative pathway of complement have been strongly linked to disease. More recently, a rare variant in the terminal pathway of complement has been associated with increased risk, Complement component 9 (C9) P167S. To assess the functional consequence of this variant, C9 levels were measured in two independent cohorts of AMD patients. In both cohorts, it was demonstrated that the P167S variant was associated with low C9 plasma levels. Further analysis showed that patients with advanced AMD had elevated sC5b-9 compared to those with non-advanced AMD, although this was not associated with the P167S polymorphism. Electron microscopy of membrane attack complexes (MACs) generated using recombinantly produced wild type or P167S C9 demonstrated identical MAC ring structures. In functional assays, the P167S variant displayed a higher propensity to polymerize and a small increase in its ability to induce hemolysis of sheep erythrocytes when added to C9-depleted serum. The demonstration that this C9 P167S AMD risk polymorphism displays increased polymerization and functional activity provides a rationale for the gene therapy trials of sCD59 to inhibit the terminal pathway of complement in AMD that are underway.

Proton Distribution Radii of

The root mean square radii of the proton density distribution in ^{16-24}O derived from measurements of charge changing cross sections with a carbon target at ∼900A MeV together with the matter radii portray thick neutron skin for ^{22-24}O despite ^{22,24}O being doubly magic. Imprints of the shell closures at N=14 and 16 are reflected in local minima of their proton radii that provide evidence for the tensor interaction causing them. The radii agree with ab initio calculations employing the chiral NNLO_{sat} interaction, though skin thickness predictions are challenged. Shell model predictions agree well with the data.

Chronically elevated depressive symptoms interact with acute increases in inflammation to predict worse neurocognition among people with HIV.

We examined the joint effects of depressive symptoms (Beck Depression Inventory-II (BDI-II)) and systemic inflammation (plasma C-reactive protein (CRP)) on longitudinal profiles of neurocognition in a cohort of 143 people with HIV (PWH) on antiretroviral therapy. Global neurocognition, processing speed, motor skills, and attention/working memory all worsened as CRP increased but only among PWH who, on average, exhibited moderate to severe depressive symptoms (BDI-II > 22). Findings suggest that some PWH with chronically elevated depressive symptoms may have an inflammatory subtype of depression and a particular vulnerability to neurocognitive changes that may respond to drugs targeting inflammation or its neural sequelae.

Dysfunction of complement receptors CR3 (CD11b/18) and CR4 (CD11c/18) in pre-eclampsia: a genetic and functional study.

OBJECTIVE: To study genetic variants and their function within genes coding for complement receptors in pre-eclampsia. DESIGN: A case-control study. SETTING: Pre-eclampsia is a common vascular disease of pregnancy. The clearance of placenta-derived material is one of the functions of the complement system in pregnancy. POPULATION: We genotyped 500 women with pre-eclamptic pregnancies and 190 pregnant women without pre-eclampsia, as controls, from the FINNPEC cohort, and 122 women with pre-eclamptic pregnancies and 1905 controls from the national FINRISK cohort. METHODS: The functional consequences of genotypes discovered by targeted exomic sequencing were explored by analysing the binding of the main ligand iC3b to mutated CR3 or CR4, which were transiently expressed on the surface of COS-1 cells. MAIN OUTCOME MEASURES: Allele frequencies were compared between pre-eclamptic pregnancies and controls in genetic studies. The functional consequences of selected variants were measured by binding assays. RESULTS: The most significantly pre-eclampsia-linked CR3 variant M441K (P = 4.27E-4, OR = 1.401, 95% CI = 1.167-1.682) displayed a trend of increased adhesion to iC3b (P = 0.051). The CR4 variant A251T was found to enhance the adhesion of CR4 to iC3b, whereas W48R resulted in a decrease of the binding of CR4 to iC3b. CONCLUSIONS: Results suggest that changes in complement-facilitated phagocytosis are associated with pre-eclampsia. Further studies are needed to ascertain whether aberrant CR3 and CR4 activity leads to altered pro- and anti-inflammatory cytokine responses in individuals carrying the associated variants, and the role of these receptors in pre-eclampsia pathogenesis. TWEETABLE ABSTRACT: Genetic variants of complement receptors CR3 and CR4 have functional consequences that are associated with pre-eclampsia.

Patient preferences for osteoarthritis pain and chronic low back pain treatments in the United States: a discrete-choice experiment.

OBJECTIVE: To quantify preferences for attributes of potential analgesic treatments for moderate-to-severe pain associated with osteoarthritis (OA) and/or chronic low back pain (CLBP) as relevant to injectable nerve growth factor (NGF)-inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), and opioids. METHODS: We used a discrete-choice experiment (DCE) to elicit preferences for attributes of OA and CLBP pharmaceutical treatments, and a best-worst scaling (BWS) exercise to further characterize the relative importance of treatment-related side-effect risks. The survey was completed online by 602 US residents with self-reported chronic, moderate-to-severe OA pain and/or CLBP who had tried, had contraindications for, or were unwilling to take currently available pharmaceutical therapies. In the DCE, respondents repeatedly chose between two hypothetical treatments defined by six attributes (symptom control; treatment-related risks of (1) severe joint problems, (2) heart attack, and (3) physical dependence; mode/frequency of administration; and cost). In the BWS exercise, respondents evaluated ten side-effect risks. Random-parameters logit models were estimated; conditional relative attribute importance, maximum acceptable risks, and willingness to pay were calculated. RESULTS: The most important DCE attributes were improving symptom control (scaled conditional relative importance, 10.00) and reducing risk of physical dependence (6.99). The three most important BWS attributes were, in rank order, risks of stroke, physical dependence, and heart attack. Respondents were willing to accept a > 4% treatment-related risk of severe joint problems for even modest symptom improvement. CONCLUSION: A pharmaceutical treatment with a risk of severe joint problems was viewed as an acceptable alternative to other treatments with comparable efficacy but risks associated with NSAIDs or opioids.

Evidence for a novel subcortical mechanism for posterior cingulate cortex atrophy in HIV peripheral neuropathy.

We previously reported that neuropathic pain was associated with smaller posterior cingulate cortical (PCC) volumes, suggesting that a smaller/dysfunctional PCC may contribute to development of pain via impaired mind wandering. A gap in our previous report was lack of evidence for a mechanism for the genesis of PCC atrophy in HIV peripheral neuropathy. Here we investigate if volumetric differences in the subcortex for those with neuropathic paresthesia may contribute to smaller PCC volumes, potentially through deafferentation of ascending white matter tracts resulting from peripheral nerve damage in HIV neuropathy. Since neuropathic pain and paresthesia are highly correlated, statistical decomposition was used to separate pain and paresthesia symptoms to determine which regions of brain atrophy are associated with both pain and paresthesia and which are associated separately with pain or paresthesia. HIV+ individuals (N = 233) with and without paresthesia in a multisite study underwent structural brain magnetic resonance imaging. Voxel-based morphometry and a segmentation/registration tool were used to investigate regional brain volume changes associated with paresthesia. Analysis of decomposed variables found that smaller midbrain and thalamus volumes were associated with paresthesia rather than pain. However, atrophy in the PCC was related to both pain and paresthesia. Peak thalamic atrophy (p = 0.004; MNI x = - 14, y = - 24, z = - 2) for more severe paresthesia was in a region with reciprocal connections with the PCC. This provides initial evidence that smaller PCC volumes in HIV peripheral neuropathy are related to ascending white matter deafferentation caused by small fiber damage observed in HIV peripheral neuropathy.

Conductance Spectroscopy of Exfoliated Thin Flakes of Nb xBi2Se3.

We study unconventional superconductivity in exfoliated single crystals of a promising three-dimensional (3D) topological superconductor candidate, Nb-doped Bi2Se3 through differential conductance spectroscopy and magneto-transport. The strong anisotropy of the critical field along the out-of-plane direction suggests that the thin exfoliated flakes are in the quasi-2D limit. Normal metal-superconductor (NS) contacts with either high or low transparencies made by depositing gold leads onto Nb-doped Bi2Se3 flakes both show significant enhancement in zero bias conductance and coherence dips at the superconducting energy gap. Such behavior is inconsistent with conventional Blonder-Tinkham-Klapwijk theory. Instead, we discuss how our results are consistent with p-wave pairing symmetry, supporting the possibility of topological superconductivity in Nb-doped Bi2Se3. Finally, we observe signatures of multiple superconducting energy gaps, which could originate from multiple Fermi surfaces reported earlier in bulk crystals.

Loss of function of NF1 is a mechanism of acquired resistance to endocrine therapy in lobular breast cancer.

Background: Invasive lobular carcinoma (ILC) as a disease entity distinct from invasive ductal carcinoma (IDC) has merited focused studies of the genomic landscape, but those to date are largely limited to the assessment of early-stage cancers. Given that genomic alterations develop as acquired resistance to endocrine therapy, studies on refractory ILC are needed. Patients and methods: Tissue from 336 primary-enriched, breast-biopsied ILC and 485 estrogen receptor (ER)-positive IDC and metastatic biopsy specimens from 180 ILC and 191 ER-positive IDC patients was assayed with hybrid-capture-based comprehensive genomic profiling for short variant, indel, copy number variants, and rearrangements in up to 395 cancer-related genes. Results: Whereas ESR1 alterations are enriched in the metastases of both ILC and IDC compared with breast specimens, NF1 alterations are enriched only in ILC metastases (mILC). NF1 alterations are predominantly under loss of heterozygosity (11/14, 79%), are mutually exclusive with ESR1 mutations [odds ratio = 0.24, P < 0.027] and are frequently polyclonal in ctDNA assays. Assessment of paired specimens shows that NF1 alterations arise in the setting of acquired resistance. An in vitro model of CDH1 mutated ER-positive breast cancer demonstrates that NF1 knockdown confers a growth advantage in the presence of 4-hydroxy tamoxifen. Our study further identified a significant increase in tumor mutational burden (TMB) in mILCs relative to breast ILCs or metastatic IDCs (8.9% >20 mutations/mb; P < 0.001). Most TMB-high mILCs harbor an APOBEC trinucleotide signature (14/16; 88%). Conclusions: This study identifies alteration of NF1 as enriched specifically in mILC. Mutual exclusivity with ESR1 alterations, polyclonality in relapsed ctDNA, and de novo acquisition suggest a role for NF1 loss in endocrine therapy resistance. Since NF1 loss leads to RAS/RAF kinase activation, patients may benefit from a matched inhibitor. Moreover, for an independent subset of mILC, TMB was elevated relative to breast ILC, suggesting possible benefit from immune checkpoint inhibitors.

A Virtual Reality Intervention for the Treatment of Phantom Limb Pain: Development and Feasibility Results.

OBJECTIVE: To describe the development of a virtual reality (VR) treatment for phantom limb pain (PLP) and phantom sensations and provide feasibility data from testing the treatment in a population of veterans. DESIGN & SUBJECTS: Fourteen participants completed a baseline visit evaluating their amputation, PLP, and phantom sensations. Subsequently, participants completed a VR treatment modeled after mirror therapy for PLP, navigating in a VR environment with a bicycle pedaler and motion sensor to pair their cadence to a VR avatar. The VR avatar enabled visualization of the participant's intact phantom limb in motion, a hypothesized mechanism of mirror therapy. SETTING: Laboratory. METHODS: Participants completed pre- and post-treatment measures to evaluate changes in PLP, phantom sensations, and rate helpfulness, realism, immersion, adverse experiences, and treatment satisfaction. RESULTS: Eight of 14 participants (57.1%) reported PLP pre-VR treatment, and 93% (13/14) reported one or more unpleasant phantom sensations. After treatment, 28.6% (4/14) continued to report PLP symptoms (t[13] = 2.7, P = 0.02, d = 0.53) and 28.6% (4/14) reported phantom sensations (t[13] = 4.4, P = 0.001, d = 1.7). Ratings of helpfulness, realism, immersion, and satisfaction were uniformly high to very high. There were no adverse experiences. Four participants completed multiple VR treatments, showing stable improvements in PLP intensity and phantom sensations and high user ratings. CONCLUSIONS: This feasibility study of a novel VR intervention for PLP was practical and was associated with significant reductions in PLP intensity and phantom sensations. Our findings support continued research in VR-based treatments in PLP, with a need for direct comparisons between VR and more established PLP treatments.

Recurrent hyperactive ESR1 fusion proteins in endocrine therapy-resistant breast cancer.

Background: Estrogen receptor-positive (ER-positive) metastatic breast cancer is often intractable due to endocrine therapy resistance. Although ESR1 promoter switching events have been associated with endocrine-therapy resistance, recurrent ESR1 fusion proteins have yet to be identified in advanced breast cancer. Patients and methods: To identify genomic structural rearrangements (REs) including gene fusions in acquired resistance, we undertook a multimodal sequencing effort in three breast cancer patient cohorts: (i) mate-pair and/or RNAseq in 6 patient-matched primary-metastatic tumors and 51 metastases, (ii) high coverage (>500×) comprehensive genomic profiling of 287-395 cancer-related genes across 9542 solid tumors (5216 from metastatic disease), and (iii) ultra-high coverage (>5000×) genomic profiling of 62 cancer-related genes in 254 ctDNA samples. In addition to traditional gene fusion detection methods (i.e. discordant reads, split reads), ESR1 REs were detected from targeted sequencing data by applying a novel algorithm (copyshift) that identifies major copy number shifts at rearrangement hotspots. Results: We identify 88 ESR1 REs across 83 unique patients with direct confirmation of 9 ESR1 fusion proteins (including 2 via immunoblot). ESR1 REs are highly enriched in ER-positive, metastatic disease and co-occur with known ESR1 missense alterations, suggestive of polyclonal resistance. Importantly, all fusions result from a breakpoint in or near ESR1 intron 6 and therefore lack an intact ligand binding domain (LBD). In vitro characterization of three fusions reveals ligand-independence and hyperactivity dependent upon the 3' partner gene. Our lower-bound estimate of ESR1 fusions is at least 1% of metastatic solid breast cancers, the prevalence in ctDNA is at least 10× enriched. We postulate this enrichment may represent secondary resistance to more aggressive endocrine therapies applied to patients with ESR1 LBD missense alterations. Conclusions: Collectively, these data indicate that N-terminal ESR1 fusions involving exons 6-7 are a recurrent driver of endocrine therapy resistance and are impervious to ER-targeted therapies.

Extreme Field Sensitivity of Magnetic Tunneling in Fe-Doped Li_{3}N.

The magnetic properties of dilute Li_{2}(Li_{1-x}Fe_{x})N with x∼0.001 are dominated by the spin of single, isolated Fe atoms. Below T=10 K the spin-relaxation times become temperature independent indicating a crossover from thermal excitations to the quantum tunneling regime. We report on a strong increase of the spin-flip probability in transverse magnetic fields that proves the resonant character of this tunneling process. Longitudinal fields, on the other hand, lift the ground-state degeneracy and destroy the tunneling condition. An increase of the relaxation time by 4 orders of magnitude in applied fields of only a few milliTesla reveals exceptionally sharp tunneling resonances. Li_{2}(Li_{1-x}Fe_{x})N represents a comparatively simple and clean model system that opens the possibility to study quantum tunneling of the magnetization at liquid helium temperatures.

Semantic fluency in deaf children who use spoken and signed language in comparison with hearing peers.

BACKGROUND: Deafness has an adverse impact on children's ability to acquire spoken languages. Signed languages offer a more accessible input for deaf children, but because the vast majority are born to hearing parents who do not sign, their early exposure to sign language is limited. Deaf children as a whole are therefore at high risk of language delays. AIMS: We compared deaf and hearing children's performance on a semantic fluency task. Optimal performance on this task requires a systematic search of the mental lexicon, the retrieval of words within a subcategory and, when that subcategory is exhausted, switching to a new subcategory. We compared retrieval patterns between groups, and also compared the responses of deaf children who used British Sign Language (BSL) with those who used spoken English. We investigated how semantic fluency performance related to children's expressive vocabulary and executive function skills, and also retested semantic fluency in the majority of the children nearly 2 years later, in order to investigate how much progress they had made in that time. METHODS & PROCEDURES: Participants were deaf children aged 6-11 years (N = 106, comprising 69 users of spoken English, 29 users of BSL and eight users of Sign Supported English-SSE) compared with hearing children (N = 120) of the same age who used spoken English. Semantic fluency was tested for the category 'animals'. We coded for errors, clusters (e.g., 'pets', 'farm animals') and switches. Participants also completed the Expressive One-Word Picture Vocabulary Test and a battery of six non-verbal executive function tasks. In addition, we collected follow-up semantic fluency data for 70 deaf and 74 hearing children, nearly 2 years after they were first tested. OUTCOMES & RESULTS: Deaf children, whether using spoken or signed language, produced fewer items in the semantic fluency task than hearing children, but they showed similar patterns of responses for items most commonly produced, clustering of items into subcategories and switching between subcategories. Both vocabulary and executive function scores predicted the number of correct items produced. Follow-up data from deaf participants showed continuing delays relative to hearing children 2 years later. CONCLUSIONS & IMPLICATIONS: We conclude that semantic fluency can be used experimentally to investigate lexical organization in deaf children, and that it potentially has clinical utility across the heterogeneous deaf population. We present normative data to aid clinicians who wish to use this task with deaf children.

HIV Distal Neuropathic Pain Is Associated with Smaller Ventral Posterior Cingulate Cortex.

Objective: . Despite modern antiretroviral therapy, HIV-associated neuropathy is one of the most prevalent, disabling and treatment-resistant complications of HIV disease. The presence and intensity of distal neuropathic pain is not fully explained by the degree of peripheral nerve damage. A better understanding of brain structure in HIV distal neuropathic pain may help explain why some patients with HIV neuropathy report pain while the majority does not. Previously, we reported that more intense distal neuropathic pain was associated with smaller total cerebral cortical gray matter volumes. The objective of this study was to determine which parts of the cortex are smaller. Methods: . HIV positive individuals with and without distal neuropathic pain enrolled in the multisite (N = 233) CNS HIV Antiretroviral Treatment Effects (CHARTER) study underwent structural brain magnetic resonance imaging. Voxel-based morphometry was used to investigate regional brain volumes in these structural brain images. Results: . Left ventral posterior cingulate cortex was smaller for HIV positive individuals with versus without distal neuropathic pain (peak P = 0.017; peak t = 5.15; MNI coordinates x = -6, y = -54, z = 20). Regional brain volumes within cortical gray matter structures typically associated with pain processing were also smaller for HIV positive individuals having higher intensity ratings of distal neuropathic pain. Conclusions: . The posterior cingulate is thought to be involved in inhibiting the perception of painful stimuli. Mechanistically a smaller posterior cingulate cortex structure may be related to reduced anti-nociception contributing to increased distal neuropathic pain.

Proton Distribution Radii of

Proton radii of ^{12-19}C densities derived from first accurate charge changing cross section measurements at 900A MeV with a carbon target are reported. A thick neutron surface evolves from ∼0.5 fm in ^{15}C to ∼1 fm in ^{19}C. The halo radius in ^{19}C is found to be 6.4±0.7 fm as large as ^{11}Li. Ab initio calculations based on chiral nucleon-nucleon and three-nucleon forces reproduce the radii well.

Tanning among Ontario adolescents pre-legislation: Prevalence and beliefs.

To establish adolescent tanning beliefs and behaviors, prevalence and location of UV tanning device (beds/lamps) use, awareness of risk and restriction signage, and frequency of tanning service refusal, noting differences by grade and sex, prior to a ban on UV tanning device use among those under 18 in Ontario, Canada. Data were collected May 5 to 20 of 2014. Children in grades 7 to 12, and under age 18 completed an on-line questionnaire that asked their age, sex, grade, methods used to tan, frequency, length and location of UV tanning device use, if services were refused and why, awareness and content of signs/warning labels, tanning beliefs and knowledge, and use of eye protection. Of 1561 participants (10% response rate), 49% were male, 51% female. There were significant differences between the sexes regarding tanning behaviors (e.g. not tanning, tanning outside). Seven percent (108) had 'ever' used UV tanning devices, females more than males (p=0.0026). Over half (57%) of the 104 using UV tanning devices in the past 12months noticed warning signs/labels, of which most noticed that UV tanning devices can cause cancer (65%), and that UV exposure can contribute to premature aging (67%). While most (66%) tanned at tanning salons/studios and beauty salons/studios, gyms/fitness clubs (35%) and home use were common (25%). A relatively low proportion of adolescents used UV tanning devices prior to the ban, with use more common among females and those in higher grades.

Design and interpretation of clinical research studies in oral medicine: a brief review.

The objective of this short review is to help researchers improve the designs of their clinical studies. Also included is a discussion of the level of evidence provided by the various clinical research study designs.

Simulation modelling as a tool for knowledge mobilisation in health policy settings: a case study protocol.

BACKGROUND: Evidence-informed decision-making is essential to ensure that health programs and services are effective and offer value for money; however, barriers to the use of evidence persist. Emerging systems science approaches and advances in technology are providing new methods and tools to facilitate evidence-based decision-making. Simulation modelling offers a unique tool for synthesising and leveraging existing evidence, data and expert local knowledge to examine, in a robust, low risk and low cost way, the likely impact of alternative policy and service provision scenarios. This case study will evaluate participatory simulation modelling to inform the prevention and management of gestational diabetes mellitus (GDM). The risks associated with GDM are well recognised; however, debate remains regarding diagnostic thresholds and whether screening and treatment to reduce maternal glucose levels reduce the associated risks. A diagnosis of GDM may provide a leverage point for multidisciplinary lifestyle modification interventions. This research will apply and evaluate a simulation modelling approach to understand the complex interrelation of factors that drive GDM rates, test options for screening and interventions, and optimise the use of evidence to inform policy and program decision-making. METHODS/DESIGN: The study design will use mixed methods to achieve the objectives. Policy, clinical practice and research experts will work collaboratively to develop, test and validate a simulation model of GDM in the Australian Capital Territory (ACT). The model will be applied to support evidence-informed policy dialogues with diverse stakeholders for the management of GDM in the ACT. Qualitative methods will be used to evaluate simulation modelling as an evidence synthesis tool to support evidence-based decision-making. Interviews and analysis of workshop recordings will focus on the participants' engagement in the modelling process; perceived value of the participatory process, perceived commitment, influence and confidence of stakeholders in implementing policy and program decisions identified in the modelling process; and the impact of the process in terms of policy and program change. DISCUSSION: The study will generate empirical evidence on the feasibility and potential value of simulation modelling to support knowledge mobilisation and consensus building in health settings.

The impact of age, HIV serostatus and seroconversion on methamphetamine use.

BACKGROUND: Characterizing methamphetamine use in relation to age, HIV serostatus and seroconversion is pertinent given the increasingly older age of the population with HIV and the intertwined epidemics of methamphetamine use and HIV. OBJECTIVES: Study aims were to investigate whether (i) methamphetamine use differs by age and HIV serostatus, and (ii) receiving an HIV diagnosis impacts methamphetamine use among younger and older persons with HIV. METHODS: This study examined methamphetamine use characteristics among 217 individuals with a lifetime methamphetamine dependence diagnosis who completed an in-person study assessment. RESULTS: Multivariable regressions revealed that HIV serostatus uniquely attenuates methamphetamine use, such that persons with HIV report a smaller cumulative quantity (ß = -0.16, p = 0.01) and a fewer number of days (ß = -0.18, p = 0.004) of methamphetamine use than persons without HIV. Among the HIV+ sample, all participants persisted in methamphetamine use after receiving an HIV diagnosis, with about 20% initiating use after seroconversion. Repeated measures analysis of variance indicated that density of methamphetamine use (i.e. grams per day used) was greater among the younger, relative to the older, HIV+ group (p = 0.02), and increased for both age groups following seroconversion (p < 0.001). CONCLUSION: These analyses indicate that although HIV serostatus may attenuate methamphetamine use behaviors, many people with HIV initiate, or persist in, methamphetamine use after receiving an HIV diagnosis. These findings raise the question of whether tailoring of prevention and intervention strategies might reduce the impact of methamphetamine and HIV across the age continuum.